VIOXX Plaintiffs News Center

Vioxx Suits Surge to Beat Deadline - washingtonpost.com

2006-10-20T05:26:00.000-07:00

Vioxx Suits Surge to Beat Deadline - washingtonpost.com: "Vioxx Suits Surge to Beat Deadline
By LINDA A. JOHNSON
The Associated Press
Saturday, September 30, 2006; 12:56 PM
TRENTON, New Jersey -- A surge of lawsuits has swamped courthouses just ahead of the two-year anniversary of drugmaker Merck & Co. pulling its blockbuster painkiller Vioxx from the market.
Saturday was the deadline for many users to sue the drugmaker over heart attacks, strokes or other harm they blame on Vioxx. Patients in 22 states, many heavily populated ones, can no longer sue Merck because they have a limit of two years on initiating personal injury lawsuits; four other states have one-year limits.

Vioxx is arranged on a counting tray, laying on top of the bottle, at The Pennington Apothecary in a Pennington, N.J. file photo from Sept. 30, 2004. A federal jury ruled in favor of Merck & Co. Inc. on Tuesday,Sept. 26, 2006, in a lawsuit over the painkiller Vioxx, finding there was not enough evidence to link the drug to a Kentucky man's heart attack. (AP Photo/Daniel Hulshizer, File) (Daniel Hulshizer - AP)

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Merck is holding its own defendin"

In Latest Drug Scandal, Ketek’s Safety and FDA Approval Are Strongly Challenged

2006-05-03T10:02:00.000-07:00

In what is undoubtedly only the beginning of another prescription drug fiasco, the evidence is mounting against both the safety of the antibiotic, Ketek, and the trustworthiness of its questionable approval by the FDA.
To be sure, the FDA has its staunch supporters among those who actually believe it is doing its best to ensure the public’s safety when it comes to approving and monitoring prescription drugs. There are also many who champion the cause of the pharmaceutical industry as being devoted to advancing the cause of human wellness and longevity.
Those who challenge these entrenched “true believers” through personal injury lawsuits or public watchdog groups are often seen as unscrupulous opportunists who do not see the forest for the trees. As the current battle over Tysabri makes clear, there are those willing to risk a 1/1000 or even 1/500 chance of dying in order to obtain a treatment for a serious disease.
While beauty is often “in the eye of the beholder,” deception, fraud, greed, and the other human moral failures are not. They are what they are for all to see and explaining them away by “spinning” the facts or reinventing history is a practice only those who seek to justify the unjustifiable engage in.
Why do responsible scientists, consumer advocates, attorneys, and the public cast such a jaundiced eye at the pharmaceutical industry and the agency they believe has come to be its rubberstamp, the FDA? Because both make it so easy to do, that’s why.
Each time a major catastrophe occurs with respect to a prescription drug, one has to ask; Was it the public, the consumer advocates, the FDA whistleblowers, the scientists, or the attorneys who were to blame, or was it an over-zealous drugmaker and completely ineffective drug approval process that caused it?
Within the past month alone, numerous articles have exposed the problem of serious potential conflicts of interest on the part of “independent” experts impaneled by the FDA for any number of advisory roles. Most of those experts are far from independent and have either long-standing relationships with the drug industry or have taken substantial sums of money from one or more drugmaker.
The absolute failure of the post-approval drug monitoring program is not a matter of conjecture; it is a matter of fact. Drug companies often fail to deliver on promises to complete drug trials, conduct follow-up studies, or provide additional documentation to support a drug’s approval. In fact, in many cases, that missing data was supposed to be provided as a condition of approval.
This is not a “red state” versus “blue state” or partisan politics issue either. The harshest critic of the FDA and the shenanigans of the pharmaceutical industry is Republican Senator Charles Grassley (Iowa). Republicans as well as democrats in the House and Senate have become quite impatient with all of the cloak and dagger goings on with respect to recent drug debacles.
Earlier this year, for example, a story was carried by hundreds of news outlets, including newsinferno.com, of an eagerly awaited diabetes drug, nearing final approval by the FDA, which significantly increases the risk of heart attacks, strokes, or death, as reported by researchers in a study published in the Journal of the American Medical Association (JAMA).
Was this an example of an isolated incident of a potentially dangerous prescription drug “slipping through the cracks” in an otherwise secure drug approval process at a responsible federal agency? Hardly.
Instead, it was yet another situation that raises serious questions concerning the reliability of the FDA’s drug approval process and whether it is unduly biased in favor of the pharmaceutical industry.
Muraglitazar, which would be marketed as Pargluva by Merck and Bristol-Myers Squib, was recommended for approval last month by an 8-1 FDA advisory committee vote.
Using the very same data the FDA panel and staff examined, however, the JAMA study researchers identified several extremely serious health concerns about the drug including almost a threefold greater risk of heart failure, heart attack, stroke,
“Ten of 1,000 patients would die, have a heart attack or a stroke,” said lead author Steven Nissen of the Cleveland Clinic. “Those are serious irrevocable events.”
The new study came from the highly respected researchers at the Cleveland Clinic, the same team that broke the story on the cardiovascular dangers of Merck’s anti-inflammatory drug Vioxx.
The researchers, including the highly respected cardiologist, Dr. Steven Nissen, found these findings to be “particularly concerning because the significant excess of adverse events was observed after only limited drug exposure ranging from 24 to 104 weeks. Real-world exposure would likely substantially amplify the risk. Taken as a whole, these data demonstrate that [Pargluva], if approved by the FDA, would constitute an unacceptable patient hazard.”
Thus, how did the FDA advisory committee that recommended the drug for approval by a vote of 8-1 ignore both the indisputable clinical data as well as the FDA’s own analysts who had themselves identified evidence of cardiac risk?
In a scenario similar to the Vioxx narrative, however, those analysts did not highlight this cardiac risk to patients as significant, except in cases where the drug was used in conjunction with other therapies.
Bristol-Myers concluded that there was no significant increase in heart risk for patients. The analogy to the Vioxx debacle is inescapable. (As Yogi Berra would say; “This is like deja vu all over again.”)
The Pargluva story is merely a small chapter in what is now becoming an all too familiar scenario of a regulatory agency being strongly influenced by the very industry it is supposed to be regulating.
This pattern is just a symptom of a more serious disease, however, and that is the premature approval and marketing of dangerous drugs which are ultimately found to pose far greater risks than any benefit they may have had.
Since the late 1990s, there has been a dramatic increase in the number of drugs that have had to be withdrawn from the market. The institution of an industry-funded “fast track” drug approval process has lead to inadequately tested drugs being rushed to market and the need for more and more serious (“black box”) warnings.
Moreover, today’s drugs are being marketed without dosing charts or information with respect to the well-known fact that each person will metabolize a drug differently.
Between 1997 and the beginning of 2005, 19 drugs have been withdrawn from the market. These include:
Palladone (hydromorphone) – 2005
Bextra (valdecoxib) – 2005
Tysabri (natalizumab) – 2005
Vioxx (rofecoxib) – 2004
Duragesic Patch (fentanyl transdermal patch) – 2004
Ephedra – 2004 (withdrawal order vacated by a federal judge)
Baycol (cerivastatin) – 2001
Raplon (rapacuronium bromide) – 2001>
Rezulin (troglitazone) – 2000
Propulsid (cisapride) – 2000
Lotronex (alosetron) – 2000
Hismanal (astemizole) – 1999
Raxar (grepafloxacin) – 1999
Posicor (mibefradil) – 1998
Duract (bromfenac) – 1998
Seldane (terfenadine) – 1997
The Diet “Cocktail”: Fen-Phen (fenfluramine); Pondimim; and Redux (dexfenfluramine) - 1997
Many see the FDA as having placed itself in a conflict-riddled position by accepting huge sums of money from the pharmaceutical industry to fund the agency’s Approval Division which is now expected to “fast-track” drugs to market. Recently, the industry portion of that funding exceeded 50% for the first time.
Unfortunately, no such funding is given to the FDA for post-approval monitoring of adverse reactions and side effects. Fast-track approvals, which are usually based on short-term testing of small test groups, have had disastrous results when used for drugs which are specifically designed for long-term or lifetime use by large segments of the population.
Once Vioxx was pulled from the market (on September 30, 2004) in the largest drug recall in history, a growing number of experts, elected officials, and public watchdog organizations began to raise serious questions about the FDA’s drug approval process.
In order to understand how the FDA’s credibility and integrity became so compromised it is necessary to take a fresh look at the FDA drug approval process as well as the necessary steps and reasons for the removal of a drug from the market.
On November 18, 2004, a federal drug safety reviewer told a Congressional panel that the FDA is “virtually incapable of protecting America from unsafe drugs.” He accused the agency easily surrendering to the demands of pharmaceutical companies.
Dr. David Graham, an Associate Director for Science and Medicine in the FDA’s Office of Drug Safety is a scientist with impeccable credentials as well as a man of unchallenged integrity who has devoted his entire professional life to making a real difference in the cause of patient safety.
Although Dr. Graham fought long and hard against Vioxx based upon the overwhelming evidence of its serious cardiovascular risks, he was little more than “a voice crying in the wilderness” who received no support within the FDA. His stunning testimony before the Senate Finance Committee chaired by Sen. Grassley can be found by clicking here.
Dr. Graham presented the evidence against Vioxx in painstaking detail. He also set forth the disturbing facts surrounding the FDA’s efforts to suppress his research, censor and alter his scientific and medical findings and conclusions, and discredit his work.
The most striking portion of Dr. Graham’s testimony involved his carefully formulated opinion that (even using Merck’s own VIGOR and APPROVe trials) some 88,000 to 139,000 Americans alone have already suffered heart attacks as a result of taking Vioxx and of that number, “30-40% probably died.” (Note that another respected expert, Dr. Eric Topol, estimated the heart attack figure to be up to 160,000).
The history of the pharmaceutical industry and its interaction with the FDA is replete with well-publicized instances of fabricating and falsifying data, concealing negative information and adverse event reports, ethical violations, conflicts of interest, undue influence, favoritism, and other forms of conduct designed to improperly influence FDA decision making.
When such factors are considered in conjunction with the administrative problems faced by the FDA on an ongoing basis, the mix is quite problematic.This is most disturbing, however, in situations where a drug, which should never have been marketed in the first place, must be withdrawn from the market. In those cases, the pharmaceutical company involved will invariably seek to avoid liability by setting up the defense that the FDA’s approval of the drug is the best evidence that the drug is safe and effective.
When it comes to approving new drugs, however, is FDA approval the “gold standard” or something dramatically less? An analysis of the FDA’s review process (generally) with particular emphasis on what occurred in the case of Rezulin demonstrates the degree to which FDA approval is open to question.
Rezulin was the first drug to be granted “fast track” status under the Food and Drug Administration Modernization Act of 1997. This meant that the FDA had only 6 months to review the NDA before Rezulin was approved in January, 1997.
The FDA Medical Office initially in charge of reviewing the Rezulin NDA (Dr. John Gueriguian) a twenty year veteran of the FDA, was removed from the project in November, 1996, only weeks before the FDA’s Medical Advisory Board was set to consider whether to recommend approval of the drug.
The removal came at the request of Warner Lambert, ostensibly because he had used intemperate language in describing the safety and efficacy profiles of the drug. Significantly, this medical officer had concluded that Rezulin was no more effective in treating diabetes than other drugs already on the market yet it had potential hepatic (liver) and cardiac (heart) side effects.
This scenario of either removing, discrediting, or ignoring the FDA’s own reviewing officer has become a recurring theme – it happened in the cases of Vioxx and Pargluva as well.
As a result of inadequate study, Rezulin was marketed in March, 1997 without any warning of liver toxicity while representing its adverse effects were no worse than those seen with placebo.
Almost immediately, the FDA began receiving reports of severe liver failure (as predicted by Dr. Gueriguian). By November, 1997, the FDA had received 35 reports of liver damage, including liver transplants and death.
Although Rezulin was withdrawn from the market in England in December, 1997 and despite the warning of the FDA’s own (new) Medical Officer, Dr. Robert Mishbin, that 12,000 patients may suffer liver damage, the FDA reaffirmed its commitment to Rezulin.
Notwithstanding the extreme dangers posed by Rezulin, the warnings lagged far behind, and required four major revisions between November, 1997 and June, 1999.
Even in the face of overwhelming evidence that the risks posed by Rezulin far outweighed any benefit the drug had, the FDA Advisory Panel did not recommend withdrawal of the drug.
On March 21, 2000 the FDA withdrew Rezulin from the market. By that time, the FDA was aware of 90 liver failures, 63 deaths, and 7 liver transplants.
Based upon the above, many experts and consumer advocates concluded that the FDA is no longer “the Gold Standard” for the safety and efficacy of a new drug. In addition to the above information, the Rezulin debacle presented additional indications that the FDA approval process is highly suspect.
Dr. Anne Peters, an endocrinologist at the University of California at Los Angeles, noted that the serious problems associated with Rezulin had been apparent while the drug was being tested.
In fact, the abnormal test results were so extreme; Dr. Peters stated that they should have been regarded as a “red flag.” Many doctors believed that Rezulin should have been marketed from the very beginning with strong warnings and the requirement that those taking the drug have frequent tests of liver function. The drug was marketed with no such warnings. (All of this is eerily similar to what happened in the case of Vioxx.)
In addition, the FDA threatened its own Medical Officer, Dr. Mishbin, with disciplinary action and dismissal from federal service for his January 24, 2000 e-mail to his superiors which stated: “I see no reason why any well-informed physician would continue to prescribe {Rezulin}.”
He also stated that he saw no reason why the “FDA should delay in taking steps to remove [Rezulin]} from the market.” Dr. Mishbin, who had originally supported the approval of Rezulin, was joined by four senior FDA physicians in calling for the withdrawal of Rezulin.
In 1999, the FDA’s own Dr. David Graham (yes, that same Dr. Graham) warned the agency’s Advisory Committee that every Rezulin user was at risk for sudden liver failure even with monthly monitoring.
Finally, Dr. Gueriguian, who was removed from the review of the Rezulin NDA in November 1996 after voicing strong reservations about the drug, saw his negative review of Rezulin purged from FDA files. Hardly a ringing endorsement of the agency’s commitment to safeguarding the public by conducting comprehensive reviews that are beyond reproach.
When the FDA announced it would hold hearings regarding the safety of COX-2 inhibitors, the hope was that the agency would finally shed its image as guardian of the pharmaceutical industry.
If ever there was a perfect opportunity for the FDA to reverse years of accusations and innuendoes concerning its questionable record in protecting the public; that was it.
With Merck’s unprecedented massive voluntary withdrawal of Vioxx, the revelation of previously unreported adverse study results, a highly respected (FDA employee) “whistleblower” and other well respected scientists poised to offer damaging testimony, the entire class of COX-2 inhibitors appeared to have “one foot in the grave and the other one on a banana peel.”
When the testimony was in and the votes counted, however, Celebrex, Bextra, and yes, even Vioxx, rose from the ashes, like the Phoenix of myth and legend, to fly again with the renewed approval of the FDA.
Of the thirty-two government drug advisers who voted on the issue, 10 had consulted for Merck or Pfizer in recent years.
When the votes were tallied, the results were shocking to many but quite predictable if the FDA’s questionable track record in protecting the public was taken into consideration.
The committee voted unanimously that all of the drugs significantly increased the risk of heart attack and stroke. Despite this finding, which could not have been otherwise, Vioxx, a drug pulled from the market by its own manufacturer (Merck) only four months before, rose from the ashes on the wings of a 17-15 vote. (Without 9 of the 10 “questionable” votes going in favor of the drug, however, the committee would have voted 14-8 to ban Vioxx).
Bextra, a drug with its own serious legal problems, survived by a margin of 17-13-2 (abstentions). (That vote would have been 12-8 against Bextra without 9 favorable votes from the 10 advisers in question).
Celebrex survived by a 31-1 margin (even though the evidence against it was equally compelling). (The vote still would have been an amazing 21-1 in favor of Celebrex without the 10 “interested” voters).
The panel did recommend all COX-2 inhibitors carry “black box” warnings. Serious? Yes. Fatal? No.
The vote was met with shock and outrage by activists, medical experts, and researchers alike. Several highly reputable news agencies like CBS News, the New York Times, and Forbes, for example, also questioned whether the panel had been “stacked” in favor of the pharmaceutical companies with advisers who had significant “conflicts of interest.”
The FDA and its safety procedures have been criticized variously by investigative reporters, activists, FDA employees, and medical experts as follows:
· “FDA Drug Oversight Fails Patients” (AP 5/23/01)
· “FDA Failing in Drug Safety, Official Asserts” (The New York Times, 11/19/04)
· “Are Too Many Unproven Drugs Receiving FDA Early Approval?” (The Wall Street Journal, 3/1/05)
· “A Rudderless, Leaderless FDA” (Los Angeles Times, 1/18/05)
· A broken agency that needs to be “fixed” (Forbes, 1/13/05)
· “Study Faults Drug Approval Mechanism” (Yahoo! News, 5/7/02)
Notwithstanding the fact that the FDA has been portrayed as a “failure” when it comes to protecting the public, such an analysis is far too simplistic.
In its 68 years of existence, the FDA has always been embroiled in the ongoing conflict between consumer safety and corporate profits. In 1927, Congress created the Food, Drug and Insecticide Administration. It was renamed the Food & Drug Administration (FDA) in 1937.
In 1933, President Roosevelt drafted legislation to strengthen the FDA and protect the public from unsafe, ineffective drugs. However, drug industry lobbyists kept the legislation trapped in committee for 5 years. Eventually, the bill was “gutted” it of its efficacy requirements.
A major disaster and a public outcry to bring about reform came in 1937, when “Elixir of Sulfanilamide,” containing a sulfa “wonder drug” mixed with a solvent closely akin to radiator antifreeze, caused 108 deaths; most of them children.
This prompted new legal requirements that safety be proven before new drugs could be marketed. The comprehensive Food, Drug and Cosmetic Act of 1938 remains the basic law governing the FDA. Drugs marketed before 1938, however, were permitted to remain on the market without proof of safety.
Being able to influence the drug approval process is the industry’s goal and it has limitless funds with which to accomplish that objective.
The reason for this is that the FDA has the potential to: (1) affect billions of dollars in pharmaceutical industry profits; (2) cause significant stock market fluctuations; (3) have an impact on pending and prospective litigation; and (4) make determinations which could (and has) actually cause a drug company to go out of business.
Unfortunately, on the other side of this “tug of war” is the noble ideal of protecting the public. Activists, “whistleblowers,” professors, and other crusaders, however, cannot even begin to match the financial and political clout possessed by the pharmaceutical industry as a whole or individual corporate giants like Pfizer, Sanofi-Aventis, Merck, Novartis, Roche, GlaxoSmithKline, J&J, and AstraZeneca.
In fact, the pharmaceutical lobby is the largest in the country. When it comes to buying “access” and influencing politicians, drugmakers are in a league of their own.
Pharmaceutical companies are in business to make money. The industry is highly competitive, with several companies often racing to be the first to market with a particular type of drug for a specific disease or illness.
Winning the race can mean billions of dollars in profits before other companies even get their drug approved. (This was the case with Viagra which, for years, monopolized the market as a treatment for erectile dysfunction until Levitra and Cialis were approved.)
The fierce nature of the competition has also flooded the market with multiple versions of the same class of drug (COX-2 inhibitors like Vioxx, Celebrex, Bextra, Arcoxia, and Prexige for example) or different treatments for the same condition (statins, resins, fibrates, and niacin for high cholesterol).
The race to get new drugs approved and on the market as quickly as possible has made (pre-marketing) long-term studies a thing of the past. As a result, the public either turns out to be the test group for long-term use or is exposed to a drug for years before on-going long-term studies disclose its dangerous side effects.
Pharmaceutical companies often claim that it is more important to get a new drug to the people that need it and that massive longitudinal studies would only delay the release of the drug.
The FDA abides by a simple yet essential question in its approval process: Do the benefits of a drug outweigh its risks? This idea of risk vs. benefit was first adopted about 30 years ago but it is now the basis for new drug approval.
The current law states that all new drugs need proof that they are effective, as well as safe, before they can be approved for marketing. The problem with the current approval process, however, is that even when the answer to this question turns out to be “no,” many dangerous drugs have either been approved or permitted to remain on the market for considerable lengths of time.
For example, Michael Elashoff, an FDA reviewer and biostatistician, was asked to review the flu drug Relenza back in 1995. Elashoff recommended against approval due to the lack of efficacy of the drug and the agency advisory committee agreed and voted 13 to 4 against approving Relenza.
Yet Relenza was ultimately approved by the FDA and Elashoff was told that he would no longer make presentations to the advisory committee. Rezulin and Vioxx were both approved and marketed for years despite the fact that strong evidence of their potentially dangerous side effects was well known while the drugs were still being tested.
In the case of Rezulin, the drug was quickly approved by the FDA despite many unanswered questions about safety and efficacy. Also, despite several indications of liver problems and the withdrawal of Rezulin in Britain, the FDA repeatedly dismissed and ignored warnings of the scientists entrusted with the responsibility of approving new drugs.
This very same failing persists today as witnessed by the Vioxx debacle. Clearly, nothing will change until either a new approval mechanism is put in place or a new agency with greater accountability and resources is formed.
Despite the complex nature of today’s drugs, the FDA is processing new drug applications at a record pace. From 1993 to 1999 the FDA approved 232 drugs known as “new molecular entities.”
This term is used to describe a new drug which does not already exist in prescription or over-the-counter form. During the previous seven years, the FDA only approved 163 new molecular entities.
Dr. Solomon Sobel, director of the FDA’s metabolic endocrine drugs division throughout the 1990s, said that there was extreme pressure to meet deadlines and complete reviews. “The basic message,” he said, “is to approve.”
It is important to know and accept the fact that all drugs have the potential to cause side effects or allergic reactions. It is also true that the list of side effects that accompany any drug will never be totally complete as there are always cases of people having unpredicted and unprecedented reactions to new drugs as well as drugs which have been on the market for years.
Many dangerous interactions between two or more drugs, between a drug and another substance like food or alcohol, or between a drug and something as common as sunlight are not discovered until after a drug is on the market.
Public Citizen, a respected public watchdog organization (www.citizen.org/hrg/), has drafted a guideline for consumers called the Seven-Year Rule which states that you should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs.
This “rule” is based on three major factors: inadequate testing, the probability that a dangerous drug will be withdrawn within seven years, and the addition of adverse reaction warnings to new drugs within their first seven years on the market.
In April of 2002, the Journal of the American Medical Association (JAMA) published a study led by Dr. Karen Lasser of Cambridge Hospital and Harvard Medical School which concluded that one in five new drugs has unrecognized adverse drug reactions (ADRs) that do not show up until after the drug has been approved.
The study analyzed 548 drugs approved from 1975 through 1999 and discovered that 56 of them were later given a serious side-effect warning or even taken off the market completely.
Dr. Sidney Wolfe of Public Citizen, who worked on the study, said: “Most troublesome drugs do not represent any advance in treatment and are at best no better than older, safer drugs already on the market.”
The study specifically focused on black box warnings, which highlight the most serious side effects that were added to the drug’s label after its release. If one of the more life-threatening side effects is not detected prior to release, it can cause major problems and create a serious hazard for the general public once the drug is on the market.
Unfortunately, once a prescription drug is approved for marketing, it is extremely difficult to have it withdrawn. Public Citizen has petitioned to have many dangerous drugs banned including the COX-2 inhibitors, Meridia, Crestor, Accutane, Xenical, and Tequin. World-renowned experts have offered clinical studies and scientific proof that numerous drugs are far too dangerous to be on the market or should not be prescribed to certain groups of patients, especially children and adolescents. Highly experienced FDA drug reviewers have advised against approving many drugs that were later withdrawn from the market.
Even though every one of these challenges was well-founded and meticulously documented, none has ever been relied upon as a basis for withdrawing an approved drug from the market. Public Citizen’s petitions have not been successful, the experts have been ignored, and (probably worst of all) the FDA reviewers have been ignored, humiliated, transferred, and otherwise discredited by their own agency.
When the FDA finally believes a drug is no longer safe to use, it will ask the manufacturer to withdraw the drug voluntarily. Usually, the company agrees and the drug is immediately pulled. Sometimes, as in the case of Vioxx, a drug is voluntarily withdrawn when the manufacturer determines it can no longer be safely marketed.
Today, most withdrawals can be traced directly to either inadequate pre-application testing, inadequate disclosure in the application process, or inadequate FDA scrutiny of existing data and expert opinions.
Although known side effects cause more injuries and deaths than unknown side effects, it can be quite unnerving for a patient to experience a reaction he or she was not warned about. Sometimes, an unknown side effect can be even more serious than the existing ones.
Limited studies (both in duration and in group size) are more likely to “miss” a particular side effect or potential risk than studies conducted on large test groups over an extended period of time.
Robert Temple, M.D., director of the FDA’s office of medical policy claims that test groups cannot be made larger and research studies cannot be dragged out since the public requires “reasonably rapid” access to needed drugs.
Unfortunately, once a drug is placed on the market, millions of people will be exposed to it for extended periods of time. Thus, short-term studies involving limited test groups offer little assurance that all serious side effects, allergies, dangerous interactions, and long-term problems have been discovered prior to marketing.
It is for this very reason that Public Citizen’s “seven-year rule” makes sense. Regrettably, during that seven year period, the public itself is acting as the test group.
The editors of the Journal of the American Medical Association (JAMA) recently made an extremely valid point about the position of the FDA. They argued that it was “unreasonable to expect that the same agency that approves drugs to also be committed to actively seek evidence to prove itself wrong.” They suggested the creation of an independent drug safety board to monitor the safety of drugs and medical devices following FDA approval, as it is no longer the “gold standard” it once was.
With all of this in mind, the Ketek story burst upon the scene yesterday in a long well-written and thoroughly researched article by Anna Wilde Mathews in The Wall Street Journal.
Taking the essential elements of that story and others that have now appeared (Reuters, etc.) it becomes obvious that what has occurred (again) is little more than “the same story, different day.”
In April 2004, Ketek, an antibiotic manufactured by pharmaceutical giant Sanofi-Aventis, was approved. That approval, however, was not without its previous problems.
In 2001, Ketek was not approved because of evidence of side-effects such as liver damage, blurred vision, and others was found in a review of the manufacturer’s earlier trials. Further support for the application was requested by the FDA before it would even reconsider Ketek for approval.
At this point, the manufacturer was eager to gain approval so it embarked on a study (labeled “3014”) that was contracted out to Pharmaceutical Product Development Inc. (PPD).
Making a very long story shot, the study that involved over 24,000 subjects was rejected by the FDA as completely unreliable. Why? Well, just for starters were the following facts:
One doctor, who was enrolling subjects at a record pace at her weight-loss clinic, turned out to have falsified data, used relatives and friends, used subjects who did not have respiratory infections, and used subjects who never even received the medication. This doctor, who enrolled 407 subjects (at $400 per subject or $162,800), is now in federal prison.
One doctor who enrolled 214 subjects was on probation at the time of the study (for gross negligence and failing to keep adequate records) and later lost his license after an arrest for domestic violence, cocaine possession, and holding a loaded semiautomatic handgun.
One doctor, who enrolled 150 subjects, was found to have committed over 20 violations of the study’s guidelines.
One doctor, who enrolled 251 subjects, failed to follow the study guidelines and did not report adverse drug reactions.
One doctor agreed to stop doing research because of serious irregularities in his data including backdating consent forms and failing to record which drugs his patients were taking.
PPD did not visit all of the test locations.
Thus, four doctors alone accounted for 1,021 (4.25% of the total) unreliable subjects whose data could not help but skew the overall results of the study. With this track record, it is difficult to imagine that the remainder of the study was any more accurate.
The $408,400 billed for the completely useless data on 1,021 subjects was a strong incentive indeed for processing data with an eye toward quantity and not quality.
Sanofi-Aventis claims that the study presented an accurate profile of Ketek despite the “deviations.” Moreover, an article in April’s New England Journal of Medicine suggested Ketek was as safe as other antibiotics. All six of the articles authors were linked financially to Sanofi-Aventis (five by consulting fees and one as an employee).
Now, as a public watchdog agency, you might expect the FDA would have steadfastly refused to approve Ketek for marketing. Clearly, the drug had failed to gain approval the first time around and its possible approval at a later date was specifically conditioned on favorable clinical test results.
When the clinical trial on which the renewed application for approval was based turned out to be full of inaccuracies, fraud, and otherwise unreliable data, the FDA was left with nothing new upon which to base an approval. Did that deter the agency, however? Not at all.
An advisory panel that met in 2003 recommended the approval of the drug although it was never told of the completely unreliable data in study 3014. The FDA then declined approval only to grant it in 2004.
Instead of erring on the side of the public, the FDA approved Ketek based on the prior data (already found to be inadequate) and the fact that the drug had been marketed in other countries with only minimal problems. Of course, this simplistic analysis ignored the well-known fact (often cited by the FDA itself) that adverse events and side effect are grossly underreported by between 90% and 99%.
Guessing that Ketek’s risk profile for liver-related problems is probably similar to other antibiotics, the FDA is currently assessing the numerous reports of liver damage while it insists that the drug is “safe and effective when used according to the label.”
Other drugs have either been pulled from the market (Rezulin) or significantly restricted (Trovan) for similar incidence rates for liver failure.
Remarkably, even though study 3014 was discredited by the FDA, the agency cited the study when agreeing with a report that suggested the drug’s safety record was reassuring. Of course, the report was based on the discredited study also. One litigation attorney we spoke with said errors like this which always favor the drug companies and not the public are unconscionable.
Senator Grassley along wit other lawmakers are already questioning the Ketek approval and the faulty and inadequate data that approval was based on. In an April 27 letter to the FDA, Grassley pointed out that the data supporting the agency’s approval was “beset by systemic data integrity problems.”
Democratic Reps. Edward Markey of Massachusetts and Henry Waxman of California also questioned the Ketek approval in a separate letter to the FDA. According to a statement from Waxman: “The Ketek case demonstrates the urgent need for reform at the FDA and in the pharmaceutical industry. FDA approved the drug on flimsy data without resolving the safety issues, and it failed to penalize Aventis.”
Amazingly, Ketek is being studied as a treatment for children with ear infections and tonsillitis although the FDA has rejected an application by Sanofi-Aventis to approve the drug for the same illnesses in adults.
When asked to comment on the FDA’s role as a public watchdog in the Ketek and other similar prescription drug scandals, a seasoned litigation attorney simply stated; “With friends like that you don’t need enemies.”

Canadian warning adds to Merck's troubles over Vioxx

2006-05-03T10:00:00.000-07:00

A new study looks set to pile the pressure on Merck as it fights to limit the financial damage from the withdrawal of its best-selling painkiller, Vioxx.
Canadian scientists are claiming that using Vioxx immediately increased the risk of heart attacks for elderly patients, undermining a key plank of Merck's defence in a slew of lawsuits from users and their families.
Merck withdrew Vioxx in 2004 after finding that long-term use was associated with heart problems, but its lawyers continue to insist that only patients on the drug for more than 18 months were at risk.
In a paper published yesterday in the Canadian Medical Association Journal, researchers at the McGill University Health Center in Montreal found that a quarter of heart attacks suffered by Vioxx users occurred within two weeks of patients starting taking the drug.
"Our previous study on COX-2 inhibitors, which included Vioxx and Celebrex, evaluated whether there was an increased risk of heart attack while taking these medications; the answer was: yes for Vioxx," Linda Levesque, the lead author of the new study, said.
The study looked at the health records of 114,000 senior citizens taking anti-inflammatories in the Quebec region over a three-year period.
The cardiovascular risk peaked on the ninth day after a patient started taking Vioxx, and actually decreased with longer-term use.
Last night Merck said that although had not seen the Canadian research, it believed the clinical trials which found an increased risk after 18 months of use provided stronger evidence than observational studies such as the Canadian research was based on.
Merck is resisting a US-wide settlement to Vioxx lawsuits, which already number 11,500 and is rising. It has lost more cases so far than it has won, as juries in several states found it knew about the risks of the drug for up to four years before taking it off the market in September 2004.
The drug's withdrawal led to the early departure of Merck's chief executive Ray Gilmartin, and his replacement by Richard Clark.
Last month, Merck said it would appeal a $32m (£18m) pay-out ordered by a court in Texas for the family of a man who had a heart attack after taking Vioxx for less than a month.

Vioxx-Linked Heart Attacks May Occur Within 2 Weeks, Study Says

2006-05-03T09:59:00.000-07:00

Merck & Co.'s Vioxx painkiller may raise the risk of a heart attack within two weeks after patients start taking the drug, earlier than previous studies have shown, according to Canadian researchers.
More than a fourth of 239 elderly patients who had heart attacks while on Vioxx did so within six to 13 days after they first started taking the drug, according to a study published online today by the Canadian Medical Association Journal.
Merck, which faces 11,500 Vioxx lawsuits, argued throughout recent trials that short-term use of the drug doesn't cause heart attacks. The company has been hit with three jury awards totaling $298.3 million, two of which involved short-term use of the painkiller. In the most recent trial, a jury on April 21 awarded $32 million to a Texas family after finding that Vioxx caused the death of a man who took it for about a month.
``For first-time users you can have an event in as little as two weeks,'' said Linda Levesque, assistant professor of epidemiology at Queen's University in Kingston, Ontario, and the study's lead researcher, in an interview today. ``Now we have evidence that early risk is possible.''
Merck spokeswoman Casey Stavropoulos couldn't comment immediately.
Merck, the fourth-biggest U.S. drugmaker, withdrew Vioxx in 2004 when a study showed it doubled the risk of heart attacks and strokes after 18 months of use. The company, based in Whitehouse Station, New Jersey, has set aside $970 million for legal costs and nothing for damages, vowing to fight each case rather than settle out of court.
`Cases Easier to Win'
Attorney Mark Lanier, who won two of the three trial victories over Merck, said the study will ``absolutely'' help in cases against Merck.
``It's going to make short-term cases easier to win,'' Lanier said. He said the Canadian findings are ``consistent with the medicine we've been talking about and all of the science except that which is funded by Merck.''
Canadian researchers analyzed health records of 114,000 patients ages 66 and older who were prescribed painkillers, including Vioxx, Pfizer Inc.'s Celebrex and ibuprofen, a non- prescription pain medication.
While about 30 percent of the patients had risk factors for heart disease, such as hypertension or coronary artery disease, none had ever had heart attacks. The study, which followed patients for about two and a half years, included 30,200 Vioxx users and 45,000 Celebrex users.
No Celebrex Link
Out of the 239 heart attacks, 65 occurred within a median of 9 days the after patients started taking Vioxx, researchers said. The study found no such statistically significant increase in risk among patients taking Celebrex.
The study also found that the risk of a heart attack associated with Vioxx didn't increase with the length of treatment and diminished after patients stopped taking the drug.
``Hopefully the study will contribute to better decision- making and put peoples' minds at ease for those who stopped the medication and may be wondering how long they have to worry,'' Levesque said.
Plaintiffs' attorneys have argued to jurors that Merck's unpublished data from clinical trials and other data show an increased risk of heart attacks after short-term Vioxx use, a claim sharply contested by the drugmaker.
``Our analysis of Merck's clinical trials shows that people have heart attacks even with short-term use of Vioxx,'' said attorney Christopher Seeger, whose firm of Seeger Weiss LLP has filed nearly 500 Vioxx suits. ``Merck has been spinning its data to show there is no risk until 18 months.''

No Defense For This Insanity

2006-05-02T12:39:00.000-07:00

Team Bush could use some fresh domestic policy. Its talk of tax reform has fizzled. Its defeat on Social Security has destroyed its hopes of fixing entitlements. Its feckless energy non-policy has come back to haunt it. Its tax cuts look ever more untenable as Iraq costs escalate. Its proposed expansion of health savings accounts is incompetently muddled. Its bungling of Hurricane Katrina's aftermath is legendary. Its trampling of civil liberties has been rolled back by the Supreme Court.
Desperate moments call for desperate remedies. President Bush should seize upon the monstrous Vioxx litigation to champion a cause that he believes in: the cause of tort reform.
Vioxx, you say? Sticking up for a painkiller that boosts the risk of heart attack is an unconventional approach to winning votes. But the Vioxx litigation -- 11,500 lawsuits and counting -- is so crazy and repulsive that it makes even drug companies look virtuous. It glorifies prejudice above science as much as Bush's stance on global warming; it wastes money as grotesquely as Bush's tolerance of pork. Everybody knows that trial lawyers are Democrats. By grabbing hold of Vioxx, Bush could do his side some good.
How do the Vioxx lawsuits glorify prejudice? Well, the first case brought against Merck, the painkiller's manufacturer, concerned a man who, according to his autopsy, had died of an irregular heartbeat -- a condition that, unlike heart attacks, is not actually associated with Vioxx. Moreover, the placebo-controlled trial that linked Vioxx to heart attacks and led to Merck's voluntary withdrawal of the drug from the market found no adverse effects until after 18 months; the alleged victim had taken the medication for only eight months. These scientific niceties didn't matter to the jury. "Whenever Merck was up there, it was like wah, wah, wah," one juror told the Wall Street Journal. "We didn't know what the heck they were talking about."
Meanwhile, the jurors had no difficulty understanding Mark Lanier, the trial attorney and decidedly unscientific Baptist preacher who brought the lawsuit against Merck. Lanier tickled their vulnerabilities and vanities, playing on local prejudices against faceless corporations from the East Coast. Knowing that one juror loved Oprah Winfrey, he insinuated that finding Merck liable might qualify her to appear on television. "I can't promise Oprah," he said artfully, but "there are going to be a lot of people who'll want to know how you had the courage to do it."
Merck's experience since that first case hasn't always been better. The company has won three verdicts, but last month it endured a second and third loss. One involved a 75-year-old diabetic who suffered from clogged arteries before he began taking Vioxx. The other involved a 71-year-old smoker and veteran of quadruple bypass surgery who had suffered a heart attack more than a decade before Vioxx even existed. Far from taking Merck's medicine for the 18 months identified as dangerous, the smoker had taken it for no more than one month, making the claimed association with his heart attack all the more implausible.
Ordinary mortals would be embarrassed to demand millions of dollars on this basis. But the way the trial bar tells it, defiance of science is a triumph rather than a scandal. "This is the first case in the country where short-term usage has been found by a jury to be causatory of heart attacks," exulted the plaintiff's attorney, skirting the question of how 12 laymen can be said to "find" medical causation. "We hope this will go a long way in dispelling this 18-month science fiction myth," the mythmaker went on.
Open societies flourish because they are driven by intelligence and information; the U.S. tort system creates an enclave of idiotic whimsy in the heart of the most open society in the world. But the Vioxx litigation does not merely celebrate dumb prejudice. It's extraordinarily expensive. For this year alone, Merck has set aside a legal war chest of $685 million. The Vioxx lawsuits could eventually cost it between $10 billion and $50 billion.
Did those numbers sink in properly? The midpoint of those estimates -- $30 billion -- is six times more than the federal government spends annually on cancer research. Or, to put it another way, $30 billion is about five times Merck's annual earnings, meaning that one of the world's top pharmaceutical research establishments is fighting for survival. At a time when Americans fret over relative decline in science and business, it's insane to sink a flagship scientific company in order to line the pockets of unscrupulous lawyers.
The first politician who says this will be called an enemy of injured victims, but he or she will also deserve to be called bold and right. Perhaps the nation could create a pool of scientific jurors -- retired doctors and such -- to hear medical cases; perhaps it could penalize lawyers who bring expensive cases that get overturned by higher courts. Whatever the solution, there's undeniably a problem. The status quo is nuts.

Dancing the FDA tune

2006-05-02T12:38:00.000-07:00

The Food and Drug Administration needs serious reform and Congress must stop dancing around the fact.
The FDA's failures over Cox-2 inhibitors were widely documented. The painkillers Vioxx and Celebrex were heavily marketed and then found to increase users' risks of heart attack and stroke. Vioxx was recalled. A Celebrex trial was halted. Now come congressional investigators with a damning conclusion to their critique of the FDA: The agency doesn't have a reliable process for tracking safety problems involving drugs already on the market.
The report by the Government Accountability Office reinforces this page's view that the FDA needs help balancing its mission of regulator for public health with its role helping get new drugs to market.
The public has little confidence in the FDA. To restore the public's trust, the FDA must become a stronger, more-assertive version of its passive self.
The agency needs a stronger hand in forcing pharmaceutical companies to conduct safety studies of drugs already in use by the public. Congress ought to get behind the efforts of Sen. Charles Grassley, R-Iowa, who has proposed drug-safety legislation requiring companies to respond with studies when safety concerns about existing drugs arise and spread.
The FDA would be given the authority to punish companies that don't fall in line with heightened safety requirements.
The pharmaceutical industry doesn't support increased requirements. But let's not forget the disclosures that drug giant Merck and federal regulators allowed Vioxx to remain on the market despite growing evidence of its dangers.
Congress should support Grassley's sharply focused reform efforts. The Iowa senator's view of the FDA is admirably lucid.
The Government Accountability Office has laid to rest any lingering doubts about the FDA: The agency fails when it comes to drug safety. Time now to fix the broken system.

Return of Direct-To-Consumer Celebrex Ads Demonstrates the Pivotal Role this Controversial Sales Tool Plays In Drug Marketing

2006-05-02T12:37:00.000-07:00

The saga of the class of drugs known as COX-2 inhibitors has provided an ongoing glimpse into a number of aspects of the multi-billion dollar pharmaceutical industry. These so-called “super aspirins,” were seen by critics as over-priced painkillers that worked no better than older, safer, and far less expensive drugs. Supporters viewed them as safe and effective drugs that were easier on the stomach than other pain medications.
The three main COX-2s (Celebrex, Vioxx, and Bextra) quickly reached “blockbuster” status and produced billions of dollars in annual sales for Pfizer (Celebrex and Bextra) and Merck (Vioxx). Massive direct-to-consumer (DTC) marketing campaigns, featuring everything from celebrity spokespersons to classic rock and roll music, kept the drugs in the public eye on a 24/7 basis.
Between January 2003 and June 2004 alone, Merck & Co. spent almost $123.9 million dollars in DTC advertising to persuade the public that Vioxx offered safe and effective treatment for acute and chronic pain associated with osteoarthritis, primary dysmenorrhea (moderate to severe menstrual pain), and other problems.Attractive actors and celebrities, like Olympic figure skating champion Dorothy Hammil, pitched the drug in carefully orchestrated commercials set to The Rascals’ 1968 hit “Beautiful Morning.”
The ad-driven popularity of the drugs, and the enormous cash flow that it created, were more than adequate to stave off challenges from consumer groups, scientists, and even FDA whistleblowers who charged that all COX-2 inhibitors were dangerous in that they significantly increased the risk of heart attacks. Even proof of manipulation of clinical study data, withholding negative information, and a complete failure of the FDA drug monitoring system were not enough to bring down these drugs.
The house of cards collapsed, however, when a study designed to gain FDA approval for even wider use of Vioxx ended abruptly in September 2004 when the cardiovascular risk posed by the drug could no longer be ignored. Vioxx was pulled from the market at that time and, despite a favorable vote by an advisory panel in February 2005, has never returned. Bextra, which had other problems in addition to the heart-risk possibility, was also pulled from the market in 2005.
Litigation that had begun while Vioxx and Bextra were on the market increased dramatically once they were pulled. Today, almost 12,000 individual personal injury and wrongful death cases are pending with respect to Vioxx and there are class-actions by private insurers and individual states to recover billions of dollars in drug-reimbursement costs from the manufacturers.
Considering the one-time popularity of these drugs, the favorable FDA panel vote, and the fact that, with Vioxx and Bextra taken off the market, Celebrex was the “only game in town,” one would have expected sales of the only remaining COX-2 inhibitor to go through the roof. That did not happen, however. To the contrary, Celebrex sales plummeted.
To many experts (financial analysts, marketing consultants, doctors, and attorneys), the key factor in dropping Celebrex sales from $3.3 billion in 2004 to $1.7 billion in 2005 was the suspension of advertising and not the Vioxx litigation or the revelations concerning the COX-2 link to an increased risk of heart attack.
DTC advertising is now the most powerful tool in the pharmaceutical industry’s arsenal in terms of generating revenue. This fact has prompted a growing concern among consumer advocates, scientists, and even legislators that the notion of marketing prescription drugs directly to the public is simply not a very good idea. Direct-to-consumer advertising was also brought up by Senator John Edwards during the vice-presidential debate as a severe problem in the medical field.
For the past several years, there has been an ongoing debate over controversial methods being used by pharmaceutical manufacturers to market prescription drugs. Recent high profile drug withdrawals and potential scandals have only intensified that debate; and no element of marketing is more controversial than direct-to-consumer advertising (DTCA).
While some experts maintain that DTCA actually strengthens our health care system, others are equally certain that DTCA has caused many of the problems that plague the drug industry (over-medicating, over-pricing, and exaggerated and often misleading advertising claims). There are even those who strongly urge that DTCA “must be banned as part of FDA reform.” (http://www.newstarget.com/z003204.html)
Many believe that any perceived benefits from DTCA are far outweighed by the problems it has caused and the burden it has placed on the FDA to regulate the content and accuracy of thousands of TV, radio, print, and online advertisements.
Before DTCA, pharmaceutical advertisements appeared only in professional publications, promotional materials, and samples intended for physicians, pharmacists, and hospital administrators.
Patients were never intended as the primary target for any form of prescription drug advertising. Thus, the commercial success (or failure) of a drug depended on its effectiveness and safety record not on slick marketing campaigns.
Today, however, the rules of the game have changed dramatically. Stiff global competition, expiring patents, generic drugs, sky rocketing research and development costs, and substantial damage awards and settlements have made marketing more important than science when it comes to turning a profit.
Moreover, a commercially successful “blockbuster” drug can mean billions of dollars in annual profits to a company. This has served as justification for bloated advertising budgets, withholding negative information, and ad campaigns that very often become deceptive and misleading.
Today, drug advertising has become an industry unto itself and inadequately tested and hastily marketed drugs permeate the market and expose the public to great risk. How did this all come about?
The first advertising specifically intended to target the consumer appeared in the early 1980s. From that time until the mid-1990s, the bulk of DTCA appeared in magazines and newspapers.
In 1997, however, the FDA issued a draft guidance (finalized 1n 1999) that permitted the expansion of DTCA into electronic and broadcast mediums. Today, DTCA is regarded as a “catchall” phrase covering all information provided by drug companies directly or indirectly to consumers. This would include traditional print advertising (newspapers and magazines), television, radio, and internet ads, and brochures, newsletters, and samples distributed by physicians and pharmacists.
In 1989 DTCA spending totaled $12 million. By 1992 that figure had jumped to $156 million. When TV and radio ads were added to the mix, spending began to take off, reaching $844 million in 1997 and $1.58 billion in 1999. The figure then soared to $2.38 billion in 2001 and is now in the vicinity of $3 billion. (Between 1999 and 2003 alone, Pfizer spent about $406.3 million on DTCA advertising for Celebrex while, during the same period, Merck spent approximately $459.8 million on DTCA for Vioxx. In 2004, Pfizer spent another $117 million on Celebrex ads.)
All of this spending is not without reward, however. A recent study by researchers at Harvard University and the Massachusetts Institute of Technology analyzed the effect of DTCA advertising on consumer spending for prescription drugs.
The study found that a 10% increase in advertising of drugs within a therapeutic drug class resulted in a 1% increase in sales of he drugs in that class. When these findings were applied to the 25 largest drug classes in 2000, it was found that every $1.00 spent on DTCA yielded $4.20 in drug sales. DTCA was thus responsible for 12% of the increase in prescription drug sales or an additional $2.6 billion in 2000 alone.
Another study conducted (between 1999 and 2000) by the National Institute for Health Care Management (NIHCM) found that DTCA resulted in significant increases in retail spending. In fact, the study found that the 50 most heavily advertised drugs were responsible for 47.8% of the increase in retail spending on prescription drugs between 1999 and 2000 (some $9.95 billion) while increases in sales of some 9,850 other drugs on the retail market accounted for 52.2% of the one-year rise in retail pharmaceutical spending (about $10.86 billion).
Other significant findings were:
Retail sales for the 50 most heavily advertised drugs rose an aggregate 32% compared to 13.6% for all other drugs combined.
The number of prescriptions for the 50 most heavily advertised drugs rose 24.6% compared to an increase of only 4.3% for all other drugs combined.
The 50 most heavily advertised drugs (in 2000) had combined sales of $41.3 billion (31.3% of total prescription drug sales).
In 2000, $125 million was spent to advertise Pepsi Cola, $146 million on Budweiser beer, $169 million on GM’s Saturn, $160 million on the top brands of Dell computers. In 2000, Merck spent $160 million on advertising for Vioxx alone.
Each of the top seven most heavily advertised drugs beat Nike’s ad budget of $78.2 million.
Each of the top 15 drugs exceeded Campbell’s soup’s advertising expenditure of $58 million.
DTCA accounted for 32% of all drug promotional spending (not counting the cost of samples).
While, in a perfect world, the benefits of DTCA touted by some experts would be understandable and even warranted, serious problems plague the system thereby making any such praise undeserved. Some of those problems include:
Repeated findings by the FDA that many ads are deceptive, inaccurate, misleading, and otherwise in violation of federal law.
The FDA is forced to expend an ever-increasing portion of its budget and manpower on policing advertising instead of more carefully investigating new drug applications and adverse reaction reports.
DTCA takes valuable assets away from research and development.
DTCA drives up the retail price of drugs.
DTCA results in over medicating the public.
DTCA results in expensive drugs being taken by patients who would be better off taking safer and cheaper alternatives already on the market.
DTCA leads people taking drugs they do not need in the first place.
DTCA eliminates the “learned intermediary” (physician) from the decision making process in many cases and, in others, doctors are placed in the awkward position of having to prescribe a drug or lose a patient.
DTCA uses celebrities, athletes, and even retired news anchors (who have no medical or pharmaceutical training) to vouch for the safety and effectiveness of prescription drugs. DTCA uses music which is (or was) popular with the target audience in order to subconsciously influence choice.
Warnings are confined to extremely small type at the bottom of the page or TV screen and rapidly spoken segments of commercials.
DTCA capitalizes on the widely held but erroneous belief among consumers that “newer is better.”
DTCA ultimately places marketing above science.
Many see the problem with the majority of prescription drug advertisements as being that they are just too slick. Critical information such as side effects or other hazards is often omitted or not explained in sufficient detail.
Some advertisements do not even specify what condition the drug is designed to treat. People supposedly suffering from extremely serious medical problems are often shown smiling and laughing or engaging in activities that make the drug appear to be far more effective than it really is.
As a result, the FDA often issues stern warnings to drug companies about misleading or deceptive statements or unproven claims of superiority. These warnings, however, are usually not made public. In fact, they are even sometimes ignored by the offending company or not acted upon for months or years.
Recently, pharmaceutical giants such as Merck, Pfizer, and GlaxoSmithKline have received warning letters from the FDA regarding the use of false or misleading advertisements and promotional materials.
Merck was warned as far back as September 2001 that its promotional activities and materials with respect to Vioxx were “false” and “lacking in fair balance.” In addition, Merck’s promotional campaign minimized the now-known serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study and warned of by reputable medical experts.
On September 17, 2001, the FDA issued an 8-page WARNING LETTER to Merck concerning its false and misleading promotional campaign. The FDA found:
“You have engaged in a promotional campaign for Vioxx that minimizes the potentially serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, and thus, misrepresents the safety profile for Vioxx. Specifically, your promotional campaign discounts the fact that the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen).”
The FDA demanded that Merck discontinue promoting Vioxx to doctors for unofficial uses and found after a review of several of Merck’s promotional conference calls and sales pitches that the promotions by Merck “are false, lacking in fair balance, or otherwise misleading in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations.” The FDA also required Merck to send letters about the deception to the medical community.
The letter dealt with so many improper and deceptive practices that it is difficult to imagine Merck, a leader in the field of prescription pharmaceuticals, had not formulated a plan to intentionally deceive the public, prescribing physicians, and the FDA itself as to the dangers posed by Vioxx. The FDA found:
1. False advertising in misrepresenting the safety profile for Vioxx;
2. Minimization of the potentially serious cardiovascular findings found in a prior study;
3. Failure to disclose the fact that Merck’s explanation for the cardiovascular incident discrepancy in a prior study was only “hypothetical” and not “demonstrated by substantial evidence;”
4. Failure to disclose that another explanation for the increased cardiovascular incident rate in the Vioxx group was that Vioxx “may have pro-thrombotic properties;”
5. Improper minimization of the Vioxx/Coumadin (warfarin) drug interaction;
6. The omission of “important risk information;”
7. Unsubstantiated superiority claims against other NSAIDs;
8. Promotion of Vioxx for unapproved uses;
9. Promotion of an unapproved dosing regimen; and
10. Misrepresenting Vioxx’s safety profile by “minimizing the potentially serious risk of significant bleeding that can result from using Vioxx and warfarin concomitantly.”
The FDA concluded that Merck’s “minimizing these potential risks and misrepresenting the safety profile for Vioxx raise significant public health and safety concerns. Your misrepresentation of the safety profile for Vioxx is particularly troublesome because we have previously, in an untitled letter, objected to promotional materials for Vioxx that also misrepresented Vioxx’s safety profile.”
Pfizer also received a warning letter (January 2005) identifying five promotional pieces for the Bextra and Celebrex which, according to the FDA’s letter: “omit material facts, including the indication and risk information; fail to make adequate provision for the dissemination of the FDA-approved product labeling; and make misleading safety, unsubstantiated superiority, and unsubstantiated effectiveness claims.”
The FDA claimed that the ads in question, such as the one featuring a woman playing the long version of a song on the guitar and a 27-minute long infomercial featuring “regular people” talking about their arthritis pain, are misleading because of their overstatement of effectiveness as well as the omission of risk information.
GlaxoSmithKline was likewise warned about misleading advertisements for its hypertension drug called Coreg.
Thus, rather than demonstrate a commitment to truthful advertising, pharmaceutical companies are viewed as likely to attempt to get away with whatever they can in terms of misleading the public.
This untrustworthiness forces the FDA to divert valuable resources (money and manpower) from other important agency functions.
DTCA has been blamed for COX-2 inhibitors like Vioxx, Celebrex, and Bextra being greatly over-prescribed for years especially to patients who never needed them in the first place.
These drugs were originally touted as being easier on the stomach than other painkillers. This led to countless prescriptions being written to people for that reason alone.
Studies have shown, however, that the vast majority of people taking COX-2 inhibitors would have tolerated older, cheaper, and safer painkillers without any significant gastrointestinal problems. We also now know that these drugs are no easier on the stomach and have even been shown to cause abdominal bleeding in certain cases.
Over-medicating is a very serious problem and it is occurring more and more frequently with respect to the most advertised drugs such as those for pain, high cholesterol, gastrointestinal disorders, depression, and disorders that cause embarrassment (incontinence, herpes, yeast and fungal infections, and erectile dysfunction).
In addition, the fact that COX-2 inhibitors cost between 10 and 15 times more than cheaper, safer, and equally effective painkillers such as naproxen, ibuprofen, and aspirin was never conveyed in any of the DTCA.
This is a common occurrence in DTCA of designer drugs and one that greatly increases the cost of healthcare. Of course as healthcare expenditures rise, so does the cost of health insurance and government programs that subsidize health benefits to senior citizens and those of limited means.
In her book, The Truth About the Drug Companies: How They Deceive Us and What to Do About It, Dr. Marcia Angell, a senior lecturer at Harvard Medical School, explains that the pharmaceutical giants are “price-gouging” Americans. According to Dr. Angell: “Many people, particularly senior citizens, simply cannot afford prescription drugs anymore.”
She says that a solution would be for drug companies to “ease up on price increases, since there is a growing public resistance, as well as resistance from employers and state governments.”
Dr. Peter Rost, a senior executive at Pfizer, argues that “if price controls came in, at first there’d be a one time fall in profits, but then they’d start climbing again and life would go on.”
Two in three Americans now believe that drug prices are “unreasonably high.” Right now, however, the drug companies are doing everything they can to avoid lowering costs such as refusing to legalize drug importation from Canada and trying to hook more and more people on what Angell calls “lifestyle drugs.” Certainly, spending billions of dollars on DTCA is not helping.
While many DTC advertisements feature unknown actors or voiceovers, a significant number of ads rely upon celebrities, athletes, and famous musical recordings to entice the public. Prominent broadcast journalists such as Walter Cronkite and Aaron Brown were used to blur the line between journalism and advertising.
These reputable news anchors, who were paid handsomely for their appearances, hosted video “news breaks” produced by a Florida company called WJMK. These ads appeared on local public television stations between regular programs.
Another company called Healthology hires journalists to appear in video Web casts for the same purpose. Critics argue that this kind of DTCA misleads viewers by “packaging promotional material to look like news.”
Morley Safer of CBS appeared in hundreds of promotional videos before deciding that the work did not meet the standards of CBS news. Although all of the news anchors involved maintain that they appeared in the videos or Web casts to advertise drugs for educational purposes only, the true purpose of these videos is to promote the drugs for retail purposes.
Dr. Steven Haimowitz, the president of Heathology said that the drug companies did not write or edit the video’s script. He claims the Web casts are “fair and balanced” and are “editorial in nature.” This type of DTCA takes advantage of the relationship between the viewer and a trusted broadcast journalist.
Pharmaceutical advertising has always been regarded by many as nothing more than “an attempt to get somebody to buy something.” Clearly, there is nothing scared about pharmaceutical ads that would make them more reliable or accurate than any other type of advertising.
In fact, DTCA advertising suffers from the very same shortcomings as advertising in general which Canadian economist Stephen Leacock characterizes as “the science of arresting the human intelligence long enough to get money from it”.
As discussed above, DTCA leads to over-medicating when consumers become convinced that the answer to their medical or psychological problems can be found in a pill.
Many people on cholesterol lowering drugs would benefit more from a healthy diet and exercise. Most people taking COX-2 inhibitors would be much better off taking older, safer, and far less expensive alternative medications.
Lifestyle changes and therapy may be more effective for certain people than the anti-depressants or social anxiety drugs they are taking. DTCA, however, will never tell any of these people this simple fact.
Although one would like to believe that a doctor will only be guided by his medical training when deciding whether to prescribe a drug, many consumer advocates believe that is not always the case.
Doctors are often faced with patients who literally demand to be given a certain drug based on nothing more than a slick TV ad. The doctor is then faced with a decision that has little, if anything, to do with medicine.
A doctor must decide if possibly losing a patient is more important than compromising his or her ethical standards. He or she must also be willing to spend the time to convince patients that the drugs they want may not be necessary or even the safest choices.
Surveys have shown, however, that doctors too can be prone to believing that “newer is better.”
Some possible solutions to the DTCA problem have been proposed. One would be to make databases with complete and accurate drug information available to medical professionals and consumers alike.
While many are in favor of such an approach, there are those who are against the release of medical data which they regard as classified to anyone outside of the pharmaceutical industry or the FDA.
Many advocate increased disclosure and posting of clinical trial results. The American Medical Association has asked federal officials to create a national database where drug companies would be required to post trial results. Such a resource would allow people to see any single drug trial, whether positive or negative, in the context of other tests relating to the same drug.
The National Institutes of Health (NIH) is also seeking more disclosure. The NIH will soon be issuing rules making scholarly articles produced by scientists getting NIH grants available to the public for free. The published work should be available within one year of publication on a government website.
The U.S. is not the only country attempting to provide disclosure of medical results to consumer. After several drug-safety scandals, Britain’s health minister said that British regulators will now begin collecting and publishing online patient reports of drug side effects.
Having more disclosure would allow doctors and patients alike to make more informed decisions about prescription drugs. It would certainly offer a reliable way to check the accuracy and completeness of claims made in DTCA or sales pitches to medical professionals.
In an expose on the pharmaceutical industry included in the November 2004 edition of the AARP Bulletin, Dr. Rost says that the pharmaceutical industry’s “relentless campaign of misinformation – the hollow arguments that are put forward to protect profits short term- will in the end backfire.”
This claim appears to have been proven by the recent Vioxx disaster. In a different context, Bausch & Lomb is suffering from the effects of a poor response to a developing crisis with respect to one of its eye solutions. Experts agree that, in the end, it is not in the best interests of a pharmaceutical company to cover up negative data about a drug.
The important thing is to determine, with the help of a physician and truthful information from the drug companies, what the correct medical decision is for the patient. Consumers should not be making these decisions. Unfortunately, this is exactly what DTCA seeks to do as one of its goals.
A well written and informative article from NewsTarget.com (February 9, 2005) states the case against DTCA as clearly as possible.
“The next thing that should be done in reforming the FDA is to reverse some of the dangerous and poorly made decisions put in place by the FDA over the last few years. The most obvious of these is the legalization of direct-to-consumer advertising by drug companies. This decision was made…with the purported goal of “educating” consumers about prescription drugs. And yet the very premise is laughable. No reasonable person could possibly believe that drug companies should be advertising prescription drugs to patients who don’t have medical qualifications to even understand if they should use those drugs in the first place. The idea of pushing these drugs to patients so that they go to their doctors and request them by name is medically reckless. It has no medical basis whatsoever. It is clearly just a ploy that was approved by the FDA to financially benefit the drug companies at the expense of public health.
It is this direct-to-consumer advertising, in fact, that is largely responsible for the over-medication of people with dangerous drugs such as Vioxx. This direct-to-consumer advertising continues today, and it is adding to the problem by creating an over-medicated nation where patients think they have to make a list of advertised drugs, then go to their doctor and request them by name. Many times, patients don’t even have any idea what these drugs do — they just see these images of happy, healthy people on television who have been hired to play roles in these drug advertisements, and the patients of course think they want to feel that way too, so they go to their doctor and request these drugs.
The whole system is absurd.”
While consumer advocates believe stricter rules and regulations are needed, the FDA is currently looking at a proposal which would allow drug manufacturers to simplify magazine and newspaper ads which are currently required to include a list of detailed information about risks and benefits. Critics of DTCA believe removing such information would be a step in the wrong direction.
Thus, as Pfizer brings its freeze on DTCA with respect to Celebrex to an end, the role of that marketing tool in generating massive amounts of income could not be clearer.
Pfizer is willing to advertise Celebrex again, even with dire warnings that, “Important Information: Celebrex may increase the chance of a heart attack or stroke that can lead to death,” because the company knows people will then begin to ask their doctors for the drug once more despite the risk. That can only translate into increased sales of a drug that has potentially deadly side effects.
Warnings have never convinced consumers to avoid a dangerous product completely. All you need to do is consider the most extreme example; cigarettes. In that case, the tobacco companies actually advertise against smoking and, still, smoking (and death from smoking) abounds.
While Celebrex remains an FDA-approved drug, the world’s biggest pharmaceutical company, Pfizer, has more than enough money to resurrect Celebrex through creative marketing. The results of Pfizer’s ad campaign will no doubt give critics of DTCA more ammunition in their fight to put an end to a system they believe is the “triumph

NicOx Raises EUR45.5 Million For Possible Vioxx Replacement

2006-05-02T12:36:00.000-07:00

PARIS -(Dow Jones)- French biotech company NicOx SA (7413.FR) Friday said it has raised EUR45.5 million to develop its HCT 3012 drug, a possible market replacement for Merck Co.'s (MRK) pulled arthritis drug Vioxx.
In a statement through the French market regulator, the company said it sold 4.55 million new shares to 43 international institutional investors at EUR10 per share.
NicOx Chief Executive Michele Garufi told Dow Jones Newswires in March that HCT 3012 could replace Vioxx and generate yearly sales of between EUR1 billion and EUR2 billion.
Merck pulled Vioxx, its blockbuster arthritis drug, off ...

Merck & Co. Is Losing Ground Following Vioxx Ruling

2006-04-07T06:36:00.000-07:00

A New Jersey jury awarded compensation of $4.5 million to one of the two plaintiffs in a lawsuit which claimed that Merck & Co.'s (MRK charts news Powerrating) Vioxx contributed to heart attacks. The jury rejected the other plaintiffs claims. Merck is currently trading lower by 1.57 on 7K shares Thursday morning on Inet.
Merck & Co. climbed to the upside during the later half of Wednesday morning and rose further during the final hour, to finish up by 0.51 at $35.99. The stock closed just below the upper end of a 7-week range at the highs of the year.

A Look at Merck & Co., Maker of Vioxx

2006-04-07T06:34:00.000-07:00

Merck & Co., the world's No. 7 pharmaceutical company by 2005 sales, was founded in New York City in 1891 by George Merck as the U.S. branch of his family's company _ German chemical manufacturer Merck, which dates to 1668. In 1902, he established a manufacturing facility in Rahway, N.J., which later added a research lab and served as Merck's headquarters until its move to Whitehouse Station, N.J., in 1992.
In 1919, Merck split his company from its German parent, now known as Merck KGaA. He later was succeeded by son George W. Merck. The company merged with Sharp & Dohme in 1953 and converted from chemical manufacturer to a pharmaceutical research and manufacturing firm.
Headquarters: Whitehouse Station, N.J.
Other key facilities: Rahway, N.J.; West Point and Upper Gwynedd, Pa.
Employees, 2005: 61,500 worldwide; of that, 31,900 in U.S.
Revenue/net income, 2005: $22 billion/$4.6 billion
CEO: Richard T. Clark
Key drugs:
_Zocor, the company's top-selling medicine and the second-most popular cholesterol drug in the country. It loses patent protection in June.
_Vytorin and Zetia, also for high cholesterol
_Fosamax, top osteoporosis treatment
_Singulair, for asthma and seasonal allergies
_Cozaar and Hyzaar, for high blood pressure

Sources: Merck & Co., health information company IMS Health

Health News Article | Reuters.co.uk

2006-04-04T04:15:00.000-07:00

Yesterday I attended the closngs in the Cona and Mcdarby VIOXX cases before Judge Higbee. Mark Lanier , Ben Morelli and Rob Gordon did a great job. The case keeps getting better from the liability perspective. Mark Lanier's analogy to the TV show Desperate HouseWives was vintage Lanier and perhaps one of the most entertaining closings I have ever witnessed . Needless to say, the jurors and everyone else in the packed Courtroom was paying attention. While you can never predict the outcome of the trial, it is clear that both sides were well prepared and the trial was hard fought.

The following are some news accounts.

Jury hears closing arguments in Vioxx trial
Mon Apr 3, 2006 9:31 PM BST
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By Jon Hurdle
ATLANTIC CITY (Reuters) - Merck & Co.'s attorney told jurors on Monday that pre-existing health problems and not Vioxx caused the heart attacks of two men suing the drugmaker, while a lawyer for one of the plaintiffs said the company deliberately hid the drug's heart risks.
The jury is expected to begin deliberations on Tuesday following Monday's closing arguments in the latest product liability suit over Merck's withdrawn pain drug.
Merck attorney Christy Jones said both plaintiffs had serious coronary blockages that had been building up for years, and that they were responsible for the attacks.
"Both of these men had serious, severe coronary artery disease," Jones told the court. "That's what caused the plaintiffs' heart attacks."
But Mark Lanier, representing one of the plaintiffs, hammered home his assertion that Merck failed to warn Vioxx users of the danger they faced because the company put profits before safety.
Lanier, the only attorney to win a Vioxx case against Merck so far, argued that Merck had become consumed by the need to make money and its corporate culture had changed in 1994 from a science focus to a commercial focus.
"Instead of hiring a top doctor or a scientist, they hired Ray Gilmartin, a businessman," Lanier said of Merck's former chief executive. "He took the company in a different direction; no longer was it science and medicine, it became strictly money. It was sales at all costs."
Lanier presented his 70-minute closing statement to the jury in the form of a TV series he called "Desperate Executives," a play on the popular series "Desperate Housewives." Lanier's fictional series consisted of four episodes: "Shoot for the Moon"; "Trouble in Paradise"; "The Cover Up"; and "Game Over."
The story, Lanier said, began with the desire to make money from Vioxx, progressed through a series of evasions and denials that the drug caused heart attacks, and ended with Vioxx being criticized by a number of scientific reports.
In her closing, Jones rejected arguments by the plaintiffs' attorneys that Merck had ignored the heart risks of Vioxx.
She said the company's top scientists, such as Dr. Briggs Morrison and Dr. Alise Reicin, both of whom testified during the trial, had gone to work for Merck because they wanted to find cures for serious diseases.
Jurors were being asked by plaintiffs' attorneys to accept that, in developing Vioxx, people like Morrison and Reicin had suddenly become dominated by a desire to make money, Jones said.
"It's not just that they put profits before safety. It's that at the time they joined Merck they suddenly didn't care any more," Jones asked jurors.
The plaintiffs are Thomas Cona, 60, of Cherry Hill, New Jersey, and John McDarby, 77, of Park Ridge, New Jersey, both long-term Vioxx users who blame the drug for their heart attacks.
Merck voluntarily pulled the $2.5 billion a year pain drug from the market in September 2004 after a study showed it doubled the risk of heart attack and stroke among people who used it for at least 18 months.
In a speech lasting two and a half hours, Jones attacked Cona's credibility, reminding jurors that he had been on the golf course shortly after his 2003 heart attack.
"He says he has limitations, that he can't walk the dog and can't walk on the golf course," Jones said. "But no doctor has limited his activities. In fact, he was playing golf within two weeks of his heart attack."
Addressing the plaintiffs' claim that Merck cared more about profit than product safety, Jones said the company continued to test the drug long after it was approved in 1999 and was no longer required to.
She argued that Merck had issued a warning in April 2002 saying Vioxx presented risks for patients with a history of ischemic heart disease, but that McDarby continued to take it for two years until his heart attack in April 2004.
McDarby's health problems included diabetes, high blood pressure, high cholesterol and the advanced age of 75 at the time of his heart attack.
"He was going to have a heart attack eventually, it was just a matter of time," Jones said.

ATLANTIC CITY, N.J. -- A jury hearing the case of two men who attribute their heart attacks to the painkiller Vioxx heard starkly different summaries of the evidence Monday, with a Merck & Co. lawyer defending its handling of the drug and a plaintiff's attorney ripping the company as desperate and dishonest.
Merck's representative, Christy Jones, said pre-existing conditions caused the men to be stricken and said Merck was above board in testing the drug, publicizing the results and responding appropriately when its problems surfaced.
"The fact is that each of these men was on a downhill slope," attorney Christy Jones told jurors during closing arguments. "They weren't blissfully walking along on some cliff, happy go lucky, with nothing to worry about, and then took Vioxx and fell off.
"They had the risk factors," said Jones, stressing a central theme to Merck's defense of the lawsuit brought by Thomas Cona and John McDarby.
But Cona lawyer Mark Lanier painted a different picture, tracing the laboratory-to-drug-store history of the arthritis drug, which Merck pulled off the market in 2004 because of links to heart attacks and strokes.
In a fiery, 75-minute monologue accompanied by a slide show, Lanier seized on Jones' statement from the start of the trial to jurors that they would be like detectives on the TV show "CSI," saying the show "Desperate Housewives" offered a more fitting comparison.
Calling the story of the Vioxx franchise "Desperate Executives," he showed a "Desperate Housewives" graphic before substituting the heads of Merck executives in place of those of the series' actresses, telling jurors Merck saw Vioxx as a potential sales dynamo that would help replace revenue lost when Pepcid and other Merck drugs came off patent.
He divided the video presentation into episodes, breaking up the narrative with "commercial breaks," showing Vioxx television ads that made no mention of the drug's heart attack risks. That was typical of Merck's marketing of the drug, which concealed or misrepresented Vioxx's safety, Lanier said.
"On a life-or-death drug, the marketing should be as transparent as glass," Lanier said. "But it was as murky as seawater."
In his closing, McDarby lawyer Robert Gordon acknowledged that the retired insurance agent was at risk for heart attack because of his diabetes, age, gender and low "good cholesterol," but said those reasons were why he shouldn't have been on Vioxx in the first place.
He was on it because Merck knew Vioxx was a risk for such users but didn't disclose it, said Gordon, who used the metaphor of five playing cards _ a 10, a jack, a queen, a king and an ace _ to represent McDarby's risk factors, with Vioxx as the ace.
"Which one's responsible for the straight?" he asked, showing jurors blowups of the playing cards. "They all are."
Merck, which faces about 9,650 lawsuits over the drug, has won two trials and lost one. But some see the cases of Cona and McDarby as a bellwether for future Vioxx litigation, since both claim to have taken the drug for more than 18 months, the point at which Merck has acknowledged that risk of heart attack and stroke increases.
Cona, 60, of Cherry Hill, says he took it for three years before being stricken on a golf course in 2003. McDarby, a 77-year-old diabetic, took it for four years before he collapsed in the living room of his Park Ridge, N.J., home, suffering a broken hip as he fell.
Both men had clogged arteries that were more likely causes of the heart attacks, Jones said during a 2 1/2-hour closing in which she reminded jurors Cona's prescription records could not account for all the Vioxx he said he had taken. His lawyers say he used free samples given by his doctors for most of the time he was on the drug.
Jones also emphasized Cona's testimony that he was prescribed Lipitor for high cholesterol in 2001 but only filled the prescription once, and that he was playing golf again within two weeks of his heart attack.
Whitehouse Station, N.J.-based Merck enjoyed runaway success with Vioxx after introducing it in 1999, but voluntarily recalled it in September 2004 after a study showed it doubled the risk of cardiovascular events after 18 months' use.
Merck tested the drug more than it was required to and the U.S. Food and Drug Administration said four times _ the last time in August 2004 _ that it was safe and effective, Jones told the six-woman, two-man panel.
"It's easy with Monday-morning quarterbacking to look back with hindsight and say you should have done this and you should have done that. That's exactly what the plaintiffs are doing in this case," she said

Doctor says Vioxx didn't kill man

2006-04-03T06:31:00.000-07:00

Testifying on behalf of Merck & Co., a cardiologist on Tuesday blamed coronary artery disease - not Vioxx - for a heart attack suffered by a man suing the maker of the now-withdrawn arthritis drug.
Dr. Barry Rayburn, a professor of medicine at the University of Alabama-Birmingham hired by Merck as a $600-an-hour expert witness, said Tuesday his review of John McDarby's medical records and clinical trials of the drug didn't support McDarby's claim that Vioxx caused him to be stricken.
But in a blow to Merck, Rayburn was barred from telling jurors his opinion that McDarby's April 15, 2004, heart attack was brought on by stress related to a hip fracture he suffered the same day.
Before testifying in front of the jury, Rayburn was questioned in court about the scope of his proposed testimony. Afterward, Superior Court Judge Carol Higbee said the doctor could not offer that opinion because he said he couldn't say "with a reasonable degree of medical certainty" that the broken hip triggered the heart attack.
McDarby's lawyers say the heart attack caused McDarby to collapse in the living room of his Park Ridge home and that his body twisted as he fell to the floor, breaking his right hip before he landed.
The trial, now in its fourth week, is the first involving long-term users of the popular arthritis drug, which Merck pulled off the market in September 2004 after a study showed it doubled the risk of heart attacks and strokes after 18 months' use.
McDarby, a 77-year-old diabetic, took Vioxx for four years before he was stricken.
Fellow plaintiff Thomas Cona, 59, whose case was combined with McDarby's for trial purposes, said he took Vioxx for three years - including after his 2003 heart attack - before it was voluntarily pulled from the market by Merck.
Rayburn said there was no evidence to show Vioxx causes heart attacks, downplaying the significance of both the clinical study that prompted the drug's withdrawal and another in which patients taking Vioxx had five times as many heart attacks as those taking naproxen.
Up to 80 percent of diabetics die of cardiovascular disease, said Rayburn, one of Merck's final witnesses in the trial.
In an abbreviated 15-minute cross-examination at the end of the day, Cona's lawyer attacked Rayburn's credibility, noting that he had allowed two of his board certifications to lapse and accusing him of "cherry picking" studies to bolster Merck's case.

Doctor testimony ends Merck defense in Vioxx trial

2006-04-03T06:30:00.000-07:00

ATLANTIC CITY, New Jersey (Reuters) - Merck & Co. wrapped up its defense in the latest Vioxx product liability trial on Thursday with testimony from a psychiatrist who said one of the men who blames the pain drug for his heart attack never mentioned taking it when discussing his medical history.
Dr. Margaret Harbison, who treated plaintiff Thomas Cona for about four years beginning in August 2000, said in a videotaped testimony that Cona never told her he took Vioxx to treat back pain.
Harbison also quoted from her medical records that said Cona was "feeling good," his family life was good and he was playing golf three months after his June 2003 heart attack.
That somewhat contradicted earlier testimony from his daughter that Cona was weak and unable to participate in family activities after his heart attack.
The plaintiff's lawyers had earlier asked the court to ban the testimony, saying some of Harbison's comments would be prejudicial to the jury.
Under videotaped questioning from Cona's attorney, Mark Lanier, Harbison admitted that Merck would likely get more detailed information on his pain medications from the doctors who were treating that condition.
"I'd think you'd get more complete information," she said.
Merck is being sued by Cona, 59, and John McDarby, 77, both long-term former Vioxx users who blame the drug for their heart attacks.
Their lawsuits are among nearly 10,000 Vioxx product liability suits that have been filed against Merck since it withdrew the $2.5 billion-a-year pain drug from the market in September of 2004.
The drug was pulled from the market after a study showed it doubled the risk of heart attack and stroke in patients who took it for at least 18 months. This trial in New Jersey state court is the first to involve long-term Vioxx users.
Lanier is the only attorney so far to have beaten Merck in a Vioxx trial, winning a multimillion-dollar jury award for a Texas widow of a Vioxx user last August. Subsequent trials in state and federal courts have gone in Merck's favor.
The plaintiffs say Merck knew the drug increased heart risks long before it withdrew the medicine from the market, but failed to adequately warn users because it placed profits ahead of safety.
"I think the evidence has showed that Merck acted responsibly in testing the medication before it was approved for market and continued to test the medicine after approval and that all the information was shared with the FDA," Merck spokesman Chuck Harrell said outside the courtroom.
Asked for his thoughts as the trial drew to a close, Lanier said: "I'd rather be sitting in my chair than Merck's.
"I don't know that we win," he cautioned. "We need the jury to say that Merck is liable."
Closing arguments for the trial, which started on March 6, are set to begin on Monday.

Scientist: Merck did not hide Vioxx data

2006-03-24T09:33:00.000-08:00

A scientist who helped develop the painkiller Vioxx yesterday rejected assertions by a plaintiff's lawyer that Merck & Co. tried to conceal from regulators unfavorable data about the popular arthritis drug's potential heart-safety problems.
Dr. Briggs Morrison defended the company's handling of a 1995 clinical study that cited positive effects of so-called cox-2 inhibitors such as Vioxx on the body, saying the data were included in Merck's 1998 application to the Food and Drug Administration to sell Vioxx.
But plaintiff's attorney Mark Lanier said Merck's new-drug application filled more than 120 boxes of documents, suggesting that Merck purposely buried data that showed Vioxx made users more susceptible to heart attacks.
''Do you think the FDA really zoned in on that one paper in those 127 boxes?" Lanier asked Morrison.
Morrison, vice president of Merck Research Laboratories, is Merck's first witness in the case, which centers on two New Jersey men who suffered heart attacks while taking the drug.

Merck to pay $475M for pain drugs

2006-03-24T09:31:00.000-08:00

Merck & Co., seeking to fill a revenue gap left by the withdrawn painkiller Vioxx, said it will pay as much as $475 million for rights to pain drugs being developed by closely held Neuromed Pharmaceuticals Inc.
euromed will receive an initial fee of $25 million and progress payments that may reach $450 million, Christopher Gallen, chief executive officer of the Conshohocken, Pennsylvania-based company, said Monday in a telephone interview.
The agreement gives Merck Neuromed's most advanced product in development, NMED-160, which is in the second of three stages of human tests needed for U.S. approval. Merck, the fourth- largest U.S. drugmaker, recalled Vioxx in 2004 after its long- term use was tied to a risk of heart attacks and strokes. Vioxx generated $2.5 billion in annual sales before being pulled.
"The market is huge," Gallen said. "It is the single-biggest market for pharma, worth about $28 billion a year."
Whitehouse Station, N.J.-based Merck is responsible for all development costs and activities, the companies said in a statement today. Neuromed, whose research unit is based in Vancouver, British Columbia, will also get research funding for two years as well as royalties from sales of the products.

Drug Sales in Developing Nations Surge

2006-03-24T09:30:00.000-08:00

Economic expansion in developing countries helped boost pharmaceutical sales in countries like China and Mexico to double-digit growth last year, outpacing sales in larger markets such as the U.S., Japan and Germany, according to a report released Tuesday.
IMS Health, which provides market information on the pharmaceutical industry, said that drug sales around the world rose 7 percent to $602 billion in 2005, but sales in China increased 20 percent to $9.3 billion and sales in Mexico rose 12 percent to $7.5 billion.
Many countries in the developing world are experiencing significant growth which is allowing them to finance health care improvements, including purchasing more drugs, said Murray Aitken, senior vice president of corporate strategy at IMS.
Sales in Latin America, for example, grew 18.5 percent to $24 billion in 2005 while revenue in the Asia-Pacific region, excluding Japan, and Africa together rose 11 percent to $46.4 billion.
Meanwhile, growth in the ten major markets _ including the United States, Canada, Japan and Germany _ rose 5.7 percent, compared to a 7.2 percent increase in 2004. Drug sales in the United States and Canada, which account for 47 percent of global pharmaceutical sales, grew 5.2 percent to $265.7 billion, a slowdown from the 8.5 percent advance in 2004.
Aitken said growth in the U.S. revenues was tempered by the loss of sales from Cox-2 pain relievers, a class of drugs which includes Merck & Co.'s Vioxx and Celebrex, and Bextra from Pfizer Inc. Merck & Co. removed Vioxx from the market in September 2004 after a study showed it doubled patients risk of heart attack and strokes after 18 months. Pfizer Inc.'s Celebrex, a drug in the same class as Vioxx , was also linked to cardiovascular problems and its sales have swooned.
Aitken also noted that as health care costs become an increasing concern in the United States, insurers are pushing consumers to use generic drugs, which are cheaper.
Last year, 94 products exceeded revenues of $1 billion, with 17 new drugs joining the category known as blockbusters. Among the newcomers were two cholesterol lowering drugs, Crestor from AstraZeneca PLC and Vytorin, which is made by a joint venture between Merck and Schering-Plough Corp.
Five drugs lost blockbuster status including Vioxx and Bextra, which Pfizer removed from the market last year at the request of the U.S. Food and Drug Administration.

Neuromed strikes major Merck deal

2006-03-24T09:29:00.000-08:00

Neuromed Pharmaceuticals Ltd., a closely held, eight-year-old biotech spinoff from the University of British Columbia, has struck a drug research deal valued at up to $500-million (U.S.) with giant Merck & Co. Inc., the richest collaboration ever in Canada that could set the stage for going public.
Still reeling from the recall of its $2.5-billion-a-year Vioxx painkiller, Merck has obtained exclusive rights to Neuromed's experimental drugs for chronic pain and anxiety, including NMED-160, which is in mid-stage trials to treat arthritis pain.
"This is a good example of what's possible in Canada, where you have a university that's very supportive of research and willing to transition that research into products," said Neuromed president and chief executive officer Christopher Gallen.
UBC professor Terrance Snutch set up Neuromed in 1998 with $3.2-million in venture capital. The initiative was based on his research to selectively block the influx of calcium into nerve cells that cause pain signals. Drugs known as calcium channel blockers have been used for several decades to treat high blood pressure and relieve heart-related chest pain.
Mr. Snutch, who is now chief scientific officer of the Vancouver-based company, took the process one step further by targeting the point where pain signals are transmitted from one nerve cell to another. That gave rise to NMED-160 as a treatment for pain that originates in nerves and inflammatory conditions, such as arthritis, instead of pain from an external injury.
By selectively regulating the concentration of calcium in cells, he said the company also has a family of compounds in addition to NMED-160 that have the potential to become new treatments for epilepsy and cardiovascular disease, and are outside of the scope of the Merck accord.
"This is a new category of therapeutics that we think has the potential to be huge," Dr. Gallen said, pointing to the last big technology platform to treat central nervous system disorders -- selective serotonin reuptake inhibitors (SSRIs), including anti-depressants such as Prozac.
He said NMED-160 has the potential to be as powerful as morphine and other opiates but without the side effects of addiction and motor function impairment.
Merck, based in Whitehouse Station, N.J., has agreed to make an initial $25-million payment to Neuromed and finance its research for two years, with an option to renew for an additional two years. Should NMED-160 win regulatory approvals globally, Merck would pay Neuromed an additional $202-million. The payments would grow to $450-million if the drug is later approved for a second use. Neuromed would also receive royalties on any sales by Merck.
Janet Skidmore, a spokeswoman for Merck, the fourth-largest U.S. drug maker, said the deal is not an attempt to replace Vioxx, which was yanked from the market in 2004 after its long-term use was tied to an increased risk of heart attacks and strokes.
She said Merck has identified pain as one of nine medical treatment areas that it is focusing on.
Dr. Gallen said Neuromed had been in partnering talks for several years with a group of pharmaceutical companies before selecting Merck because of its research, clinical development and ability to market pain drugs.
Earlier this month, the company raised $25-million in its fourth round of venture capital financing, for a total of $76-million since 1998. "Up until now, we've been focused on development, financing and partnering, but now we will strongly consider an IPO [initial public offering]," Dr. Gallen said.
The deal
- Merck gains exclusive rights to Neuromed's experimental drugs for chronic pain and anxiety, including NMED-160
- Merck pays $25-million up front and finances Neuromed's research for two years, with an option to renew for two more years.
- Should NMED-160 win regulatory approvals globally, Merck would pay Neuromed an additional $202-million.
- Payments would grow to $450-million if it is approved for a second use.
- Neuromed receives royalties on any Merck sales.

Courthouse bomb scare delays Vioxx trial

2006-03-24T09:27:00.000-08:00

A high-profile drug liability trial was delayed briefly Wednesday when a device believed to be used in bomb detection training was discovered in the courthouse, authorities said.
Authorities evacuated the Atlantic County Civil Courthouse, where two men's case against Merck & Co. over its withdrawn painkiller Vioxx is in its third week, at about 8:06 a.m. after a sheriff's deputy discovered it in the drawer of a first-floor office, said Atlantic County Undersheriff John Tuohy.
About 100 people poured into the street as bomb technicians, police and firefighters responded, said Lt. Michael Tullio, a spokesman for the city police.
The device looked like a pipe bomb, with nails, wires, a battery and electrical tape wrapped around it, according to a courthouse employee who saw it but declined to give his name.
"It looked real, put it to you that way," said Tuohy. "Could it have been live? I don't know."
Tullio said the device was apparently left behind after a training exercise, although neither Tuohy nor Tullio knew how long ago that may have been.
Tuohy said it has been at least four years since such an exercise was held in the building because of more sophisticated screening equipment at the entrances.
"They believe it was a training aid that was secured and forgotten about and then found, and because nobody knew when and there's this national trial going on, they decided to err on the side of caution," said Tullio.
The three-story building, located two blocks from the famed Atlantic City Boardwalk, was declared safe about 9:40 a.m. and workers were allowed back in then.
The Vioxx trial, which had been scheduled to begin about 9:30 a.m., resumed about 10:20 a.m.

Vioxx plaintiff weakened by heart attack: daughter

2006-03-24T09:26:00.000-08:00

The daughter of a man who blames Merck & Co.'s Vioxx arthritis medicine for his heart attack cried on the witness stand on Monday as she told a New Jersey court that her father had lost much of his strength since the June 2003 attack.
In emotional testimony lasting about 30 minutes, Jackie Cona, 23, said her father Thomas Cona had been athletic and had played an active role in her childhood and that of her sister Jamie, 28. But his heart attack had left him weak and unable to participate in normal family activities.
"He's like my grandfather, that's not my dad," she said, tearfully, in response to questioning from one of Cona's attorneys, Benedict Morelli.
Jackie Cona, a graduate student of speech therapy, told the jury of seven women and two men that her father now can't walk more than about 25 feet without resting, and sometimes takes morning naps, which he would never have done before his heart attack.
Thomas Cona, 59, and John McDarby, 77, are suing Merck in the latest product-liability suit over Vioxx, which the company voluntarily withdrew in September 2004 after a study showed the risk of heart attack and stroke doubled in patients who took the drug for at least 18 months.
Both Cona and McDarby took the pain drug for more than 18 months.
Cona, an avid golfer, told the court last week that he had returned to the golf course 10 days after his heart attack, and acknowledged that he had played golf 57 times during the remainder of 2003, and more than 60 times in both 2004 and 2005.
On the day of Cona's heart attack, his daughter said she visited him in the hospital. "He was white as a ghost, tubes everywhere, IVs, bags hanging," she told jurors in Atlantic County Superior Court.
"Every time that monitor went off, my heart kind of jumped because I had never been in a hospital before," she told the court. "I could see in his eyes he was scared. I just remember him saying, 'I'm just too young for this.'"
At the end of testimony in which she often struggled to keep her composure, Jackie Cona said she faces the possibility that her father may not live to see her married. "My dad might not be able to walk me down the aisle," she cried.
Almost 10,000 people have filed lawsuits against Merck, claiming the company was long aware of heart risks associated with Vioxx but failed to adequately warn users of its dangers because it put profits before safety.
Merck has said it will fight each case.
This trial -- the second state trial in New Jersey, where about half the cases have been filed -- is the first to hear cases of long-term Vioxx users.
In the first New Jersey trial, an Atlantic City jury last year denied a claim by Idaho postal worker Frederick Humeston that Vioxx had caused his heart attack.
Jurors said after the trial they thought Humeston's attack had been caused by his preexisting health problems rather than by Vioxx.
Only one plaintiff has so far won a Vioxx suit. A Texas jury awarded $253 million last August to the widow of a Wal-Mart worker who had taken Vioxx and died from a heart attack. Merck is appealing that verdict.

Merck buys drug to plug Vioxx sales gap

2006-03-24T09:24:00.000-08:00

In a move to fill a huge sales gap left when it pulled Vioxx from the market nearly two years ago, Merck & Co. agreed to pay up to $475 million for the rights to experimental pain treatments being developed a privately-held biotech firm. Whitehouse Station, N.J.-based Merck will pay Neuromed Pharmaceuticals Ltd. an initial $25 million in cash for the right to research, develop and sell Neuromed’s experimental pain treatments, including the firm’s lead product -- NMED-160 -- currently in mid-stage clinical trials.
If NMED-160 is successfully developed and launched, Merck would pay $202 million in milestone payments, which could grow to $450 million if the drug is later approved for a second use. Neuromed would also receive research funding for two years and Merck would make additional payments if other compounds were developed under the terms of the agreement. Merck, which lost $2.5 billion when it withdrew its Vioxx pain killer from the market in September 2004 because of heart attack and stroke risks, has been battling numerous product liability lawsuits related to the drug. The drug maker won two cases -- one Federal and one in New Jersey -- but there are still more than 9,600 lawsuits outstanding. Neuromed was founded in 1998 as a spin-off from the University of British Columbia.

Time Limits Planned for Next Vioxx Trial

2006-02-27T06:40:00.000-08:00

The wheels of justice will spin a little faster at the next Vioxx trial. A pair of chess clocks will see to that.
Determined to keep it short, lawyers for Merck & Co. and two men suing the painkiller's manufacturer have agreed to time limits on testimony and will use tabletop clocks _ activated manually, each time one side or the other puts a witness on the stand _ to keep track.
When the trial begins March 6, lawyers for plaintiffs Thomas Cona and John McDarby will have 40 hours to present their cases, not including opening statements and closing arguments. Lawyers for Merck will get 35.
The idea is to accelerate the battles in the massive legal war over Vioxx, an arthritis drug pulled off the market in 2004 after being linked to heart attacks and strokes with long-term use. More than 9,650 suits have been filed in state and federal courts by former Vioxx users or their survivors, who blame the drug and say its Whitehouse Station, N.J.,-based manufacturer should be held accountable.
With Merck vowing to fight them one by one, many involved are looking for ways to speed up the process _ without sacrificing justice.
It's the legal equivalent of a hurry-up offense.
"Lawyers are like gas. We fill up whatever room we're provided," said Robert Gordon, an attorney for McDarby. "Often times, judges need to assert some sort of reasonable control. If Merck is to be taken at their word, they're never going to settle _ and there's 10,000 cases to go. The court system's going to have to be creative in adjudicating the cases."
The idea for the clocks came after state Superior Court Judge Carol Higbee _ who presided over a Vioxx trial that took seven weeks last fall _ asked the lawyers for ideas on how to limit the next one's length. Cona's lawyer, Mark Lanier, a chess enthusiast, suggested the clocks _ and even provided them.
Merck's lawyers argued for equal time, but plaintiff lawyers persuaded Higbee to give them five hours more, since they have to lay the medical and factual foundation from which both sides will build.
It's common for judges to keep tabs on how much time lawyers are taking in a trial, but one veteran product liability lawyer said he'd never heard of a court imposing time limits _ or using chess clocks to enforce them.
"In my 36 years experience, I've never been under any kind of clock, chess or otherwise," said Alan Klein, of Philadelphia. "Judges move cases along, that's their function. But I've never heard of having to punch a clock."
If either side asks for more time because of issues that arise during in the trial and Higbee says no, it could be grounds for appeal, he said.
Vioxx, a pain reliever marketed to arthritis sufferers, hit the market in 2000 and was a $2.5 billion-a-year blockbuster for Merck, quickly becoming a godsend for thousands of people with chronic pain who suffered gastrointestinal side effects while taking other types of pain relievers.
Merck has dug in its heels for the courtroom wrangling over it, setting aside $970 million to defend itself against personal injury suits but no money for settlements.
To date, Merck has won twice and lost once in Vioxx trials. But some see the impending Cona/McDarby case as a bellwether for what lies ahead, since it's the first involving a patient who used the drug long term.
Cona, 59, of Cherry Hill, said he took the painkiller for more than two years before suffering a heart attack in June 2003. McDarby, 76, of Park Ridge, a retired insurance salesman, took Vioxx for four years without incident until he suffered a heart attack in April 2004.
Chuck Harrell, a spokesman for Merck's legal team in the case, said the company treats each case individually.
"Every case is different. We're going to try each case, one at a time. Each one has different facts," he said. Asked if Merck was optimistic because of its victory last week in a federal Vioxx trial, he said: "We have optimism in every case that we try."
Lanier, a colorful Texas attorney who won a $253 million judgment against Merck last summer in the first Vioxx case to go to trial, is already an issue in this one.
In a Feb. 6 motion, Merck's lawyers asked Higbee to keep a tight rein on Lanier, accusing him of casting aspersions on Merck's attorneys, promoting himself and misrepresenting testimony to jurors in the Texas trial. Merck's lawyers cited 14 instances in which they contend Lanier overstepped his bounds in that case.
"I don't mince words. I speak bluntly, and I'll continue to do that," Lanier said in an interview. "Remember, this is coming from a company that, in the last (New Jersey) trial, engaged in a shouting match with the judge. I promise I won't do any of that. We just need to be nice and polite _ to the court, to the jury, to each other."
Lanier may call former Merck Chairman and CEO Raymond Gilmartin as a witness. Gilmartin, who retired last year, was head of the company when Vioxx was voluntarily pulled off the market by Merck. But he has yet to testify in person in any of the trials.
Jury selection for the trial begins Monday.

Vioxx litigation draining Merck

2006-02-27T06:37:00.000-08:00

Vioxx is hardly the only reason Merck's stock has tumbled 63 percent from nearly $95 in November 2000.
Earnings have slipped in recent years as competition from generic products has cut into revenues. The company has also struggled to produce a new blockbuster drug the likes of Vioxx or the $4 billion a year cholesterol fighter Zocor.
But as jury selection begins Monday in state Superior Court in Atlantic City in the next Vioxx trial, analysts believe the ongoing litigation will likely serve as a drag on the stock price even as the Whitehouse Station-based drug maker appears to be regaining its footing.
Typical of many analysts' comments are those of John Boris of Bear Stearns, who wrote in a recent note to investors: "We see only limited upside to the stock, since earnings growth is not expected to resume for Merck until 2009 and the litigation news flow on Vioxx in the near term will be a major overhang."
Merck is facing more than 9,600 Vioxx lawsuits.
Nevertheless, CEO Richard Clark said last month that savings have already begun to accrue from a restructuring plan designed to shave $4 billion in expenses through 2010. Moreover, Clark said earnings growth should begin to pick up steam again as early as 2007 as revenue from new products starts rolling in.
Already in 2006, Merck has received approval for RotaTeq, a vaccine for preventing a common but serious gastrointestinal virus in children. And approval is expected later this year for Gardasil, a cervical cancer vaccine, and Januvia, a treatment for Type 2 diabetes.
Investors have responded, raising the stock price about $10 since it closed at a recent low of $25.85 on Oct. 7, about six weeks after a Texas jury awarded the widow of a Vioxx user $253.4 million in damages. The stock closed down 31 cents to $35.10 on Friday.
John P. Wilkins, president of Wilkins Investment Counsel, a Boston-based advisory firm that owns Merck shares, believes investors have been unduly influenced by the Vioxx litigation.
"In my 32 years of experience, I've never seen hysteria as severe as it was regarding the Vioxx recall," he said.
Indeed, the stock plunged $12 -- from $45 to $33 -- on Sept. 30, 2004, the day Merck withdrew Vioxx from the market based on research that showed the popular painkiller doubled the risk of heart attacks and strokes after 18 months of use.
Wilkins noted that Wall Street has reduced Merck's potential liability since the drug was withdrawn.
Moreover, taking into account Merck's restructuring plan -- which includes cutting 7,000 jobs and closing five facilities -- and the company's announced intent to refocus its research and development in areas "where Merck has particular competence," Wilkins believes the stock may represent a bargain at its current price.
"If you agree that it was [Vioxx] hysteria" that drove the stock down in the first place, he noted.
Since losing in Texas last summer, Merck has won the two most recent trials.
A jury in Atlantic City ruled in favor of Merck in November in the case of an Idaho man who had used Vioxx for about two months. And in a retrial of a case that ended late last year in a hung jury, a federal jury in New Orleans cleared Merck on Feb.17 of responsibility in the death of a Florida man who had used Vioxx for less than a month when he suffered a heart attack.
The trial that opens Monday, which combines two cases, poses new challenges for Merck, however.
First, the plaintiffs, John McDarby of Park Ridge and Thomas Cona of Cherry Hill, both say they were long-term Vioxx users. Plaintiffs in the earlier trials were short-term users.
McDarby, 76, said he took Vioxx for more than four years before suffering a heart attack in April 2004. And Cona, 59, said he took Vioxx for two years before his heart attack in June 2003.
"I'm going to show the jury Merck's own study, which shows the longer you use Vioxx the greater the chance of having a heart attack," said Robert Gordon, a product liability trial lawyer with the firm Weitz & Luxenberg, who is representing McDarby.
Second, Merck on Thursday had its request to have the trial separated into two cases denied by Superior Court Judge Carol Higbee, who chose to consolidate the cases.
Merck officials have insisted since the first Vioxx case was filed in May 2002 that the company plans to fight each lawsuit individually because each case is different and must be argued on its own unique set of facts. The company has set aside $685 million to cover legal fees stemming from the suits.
Blending the cases will double the already voluminous amount of information that jurors will need to digest, a fact that will likely cause confusion and tilt the scales against Merck, the company's lawyers have argued.
Higbee dismissed that argument on Friday, saying the McDarby and Cona cases are similar enough to be heard by one jury.
Gordon believes consolidating the trials is the only way all of the Vioxx plaintiffs will get their day in court. The court system isn't equipped to efficiently handle all the cases waiting to be tried, he said.
"It's not possible for the court system to address the problem without consolidating trials," he said. Besides, he added, "There's no reason a jury can't determine causation in more than one case at a time."
Opening statements are expected on March 6.
E-mail: prial@northjersey.com

FDA review hampered by the ghost of Vioxx

2006-02-24T08:56:00.000-08:00

The FDA wants more funding to help speed up its drug review process, which could help drug makers by getting products on the market faster, but the agency might need to drop its fear of deadly new drugs if it really wants to benefit the industry and patients.
As part of its nearly $2 billion budget proposal, the Food and Drug Administration is asking for a $71 million increase, including $6 million for Critical Path, its effort to streamline the drug review process. The FDA has set a review time goal of 10 months for standard drugs and six months for fast-track drugs with life-saving potential in areas like cancer and heart disease.
Will this budget increase – assuming it gets approved by Congress – translate into future revenue for drug makers? It might, says Fran Hawthorne, author of "Inside the FDA," but it's hard to say how much.
Each month that a potential blockbuster spends going through the review represents about $40 million that it could be generating on the market, said Hawthorne. The $6 million that the FDA is seeking for Critical Path could translate into the hiring of dozens of new reviewers, said Hawthorne, noting that each reviewer works on about a dozen drugs at a time.
"Each reviewer's salary is $100,000 at a rough estimate, so it could pay for a lot of reviewers," said Hawthorne. "That's the biggest problem, the lack of people, and that's what creates the biggest time pressures."
More staff isn't the only thing the FDA needs, said Sherry Hayes, director of regulatory analysis for Ernst & Young. Hayes said the FDA proposal, which has been included in the president's budget, would go towards staff, resources and the technology needed to review genomics-related drugs from biotechs, as well as the review of medical devices and the funding of collaboration with research institutes. So if the FDA shaves a couple of months off its review process, that potentially means more revenue for drug makers and more life-saving drugs for patients in need.
"I think it can mean a lot, obviously, for the investment community," said Hayes. "A couple of months on the market means a lot for the companies if they've got their ducks in a row [to manufacture and market the drug immediately.] From a patient's perspective, there are people whose whole lives hang in the balance in those 60 days."
FDA's fears of another Vioxx
Here's where the FDA faces a double-edge sword: Even if patients are dying every day for want of experimental drugs that languish in bureaucracy, the agency is haunted by the ghosts of Vioxx, Tysabri, Bextra, Palladone and Phen-fen, to name a few of the drugs that the agency approved, then later withdrew from the market because of health risks that slipped through its review process. Recently, the FDA has also weighed the risks of suicidal thoughts in teenagers taking antidepressants and heart attacks in children taking stimulants for attention deficit hyperactivity disorder.
Sam Kazman, an expert with the Competitive Enterprises Institute, said the FDA stymies itself by juggling fears of "Two sorts of mistakes: You can approve something that later turns out to be a disaster. On the other hand, you can delay a drug that's really needed, and people suffer medically as well."
The FDA doesn't want another Vioxx: the arthritis painkiller that it approved but then Merck withdrew in 2004 after a study showed an increase in heart attacks and strokes in patients who took the drug for at least 18 months. Since the withdrawal, nearly 10,000 lawsuits have been filed against Merck, blaming the company for fatal and non-fatal heart attacks.
Nonetheless, Kazman believes the FDA is erring on the side of caution.
"Caution sounds like a great thing, but if I'm drowning and you're going to throw me a rope, but you want to make sure that the rope conforms to all federal standards, well by then I've already gone under," said Kazman. "The general attitude at the FDA has been, 'You can either have it done fast or you can have it done right.' You just got to have people understanding how much is at stake."
Kazman said the FDA worries about approving potentially deadly drugs because the agency is directly accountable, while it's not held accountable for patients who die because new drugs aren't being approved quickly enough.
"I think that the most of what is required at the FDA to speed up drug approvals has more to do with the agency's attitude than with funding," said Kazman.
Hawthorne, the author, said there's no way to detect all side effects for drugs before they go on the market, making risk inevitable. She said the laws for post-market review should be strengthened to mandate post-market safety tests and "to give the FDA absolute authority in imposing label changes without having to negotiate with the drug companies."
But even a streamlined FDA review won't pull Big Pharma out of its industry-wide slump, said Hawthorne.
"The problem isn't with the FDA not approving drugs fast enough; it's that the drug industry isn't coming up with enough new drugs," said Hawthorne.

Merck: Two Vioxx cases shouldn't be consolidated into one trial

2006-02-24T08:53:00.000-08:00

Merck & Co. has filed a motion opposing a judge's plan to consolidate two Vioxx cases into one trial, saying their differing circumstances would make for a "Frankenstein's monster" of a case for jurors to consider. State Superior Court Judge Carol Higbee has consolidated the cases of Thomas Cona and John McDarby for the Feb. 27 trial, but Merck _ which pulled the popular arthritis drug off the market in 2004 _ said in a motion filed Friday that the facts, evidence and witnesses presented to make each man's case would confuse the jury and hurt Merck's chances for a favorable verdict.
Cona, a 59-year-old businessman from Cherry Hill, said he took Vioxx for more than two years before suffering a heart attack in June 2003. McDarby, 76, of Park Ridge, said he took the drug for two years before being stricken. "(F)aced with a Frankenstein's monster of a trial involving a jumble of evidence," Merck attorney Hope Freiwald wrote as part of her in the 26-page motion, "... jurors would inevitably be unable to divide their brains in half and restrict their consideration of evidence to the case for which it is admissible while ignoring that same evidence in the other case where it is not." Disparities between Cona and McDarby's cases will make it tricky for jurors to consider both claims at once, according to Freiwald's 26-page motion. For example, Merck's understanding of the risks posed by Vioxx was different when the drug was prescribed for McDarby than it was 17 months later when Cona had it prescribed, and evidence presented on Cona's behalf could taint the jury about McDarby's claim, according to Merck's motion. "A jury that is confused and uncertain, as any jury facing a consolidation of these two cases would necessarily be, will most likely resolve that confusion in favor of the sympathetic plaintiffs and against the big pharmaceutical company," the motion said. McDarby's lawyer accused Merck of wanting to sever the cases so that the Vioxx litigation drags out. "Merck doesn't want to consolidate cases because they want to stall the litigation and trickle cases out of the system and starve out the plaintiffs so they take less money," said Perry Weitz. "Fortunately, I think our judiciary is too savvy and won't fall for that." He said trying two cases at once would not prejudice jurors. No date has been set for a hearing on Merck's motion. Merck & Co., which is based in Whitehouse Station, pulled Vioxx from the market in September 2004 after research showed it doubled the risk of heart attacks and strokes after 18 months' use. In the first New Jersey trial, a jury dismissed a claim that Vioxx caused the heart attack of an Idaho postal worker who had been taking the drug for about two months. The company faces about 9,650 lawsuits filed by former Vioxx users. So far, Merck has won one, lost one and had one mistrial declared.

How a law firm races to repair its Vioxx files

2006-02-24T08:52:00.000-08:00

Hurricane Katrina destroyed a lot of things, but some of the most difficult to replace are legal files.
That is the dilemma facing the New Orleans law firm of Herman, Herman, Katz & Cotlar. The firm oversees a repository for 10 million documents relating to federal litigation of Merck & Co.'s painkiller drug Vioxx -- including medical reports, depositions and emails -- that plaintiffs' lawyers are permitted to use. Those documents were housed on the 43rd floor of an unharmed office building during the hurricane and stayed dry.
But many of Herman's own 125 federal Vioxx cases were waterlogged, and the firm is scrambling to recreate those documents to meet a court deadline Thursday to turn over files for 90 of those cases to Merck's defense team. That means using a private investigator to track down many plaintiffs whose homes were destroyed, and for whom litigation is the last thing on their minds.
A typical response from plaintiffs once they are found: "'I hadn't even thought about that. I've been busy trying to get things like shoes,'" recalls private investigator Anthony Valenti, a 67-year-old retired police officer.
The law firm is operating with half of its 65-person staff since it returned to temporary offices in the Big Easy in early January. Several employees lost everything, including Leonard Davis, a partner at the firm, and his paralegal.
"We're having a hell of a time," says partner Russ Herman. "We've got medical records destroyed at three hospitals that don't exist anymore."
Merck withdrew Vioxx from the market in Sept. 2004 after it was linked to an increased risk of heart attacks and strokes. The Whitehouse Station, N.J., drug giant faces 9,650 Vioxx cases in state and federal courts.
Katrina has caused other serious problems for the 4,350 federal cases consolidated under U.S. District Court Judge Eldon E. Fallon in New Orleans. The first federal Vioxx trial was relocated to Houston after the hurricane, and ended in a mistrial in December. The retrial started in New Orleans on Feb. 6.
The Herman firm plays a critical role in the federal Vioxx litigation at large. It was appointed by Judge Fallon to serve as an intermediary between the court and plaintiffs' attorneys around the country.
After the storm, the Louisiana governor extended the deadline for filing a case. After that, lawyers have 75 days to turn over files that include questionnaires filled out by plaintiffs and their medical records. The deadline for the Herman firm to submit completed forms to Merck is Thursday -- otherwise, Merck can ask the court to dismiss the cases. Merck liaison counsel Phil Wittmann says Merck has "routinely granted extensions to Mr. Herman and other Louisiana counsel in cases where they've had trouble completing the forms due to Katrina....If Mr. Herman calls me and explains what his problem is, we will grant his extension."
Following the storm, Herman sent letters to clients asking them to send information on their new locations. Almost no one responded. Mr. Valenti started tracking them down using credit card numbers, motor vehicle records and cellphone numbers. He located one plaintiff by obtaining the name of the man's auto insurer from motor vehicle records. The client had been in a car accident and was found living in Brookhaven, Miss.
Since many doctors' and hospitals' records were destroyed in the storm, Herman has been reaching out to third party companies that archive medical records, and even photocopy companies to see if they have them.
Mr. Herman says he is frustrated that he's been unable to locate Allen Rosenzweig, his jury consultant. Mr. Herman told Mr. Valenti, the private investigator, that Mr. Rosenzweig's father was a tailor named Murphy and his mother was named Florence, and he joked that the jury consultant "was crazy enough to be on the top of a roof someplace." Mr. Valenti, the private investigator, came up with a post office box in Kenner, La., and a phone number. The voice on the answering machine said it was Mr. Rosenzweig, but the jury consultant still hasn't been found.
A week after the storm, Herman staffers returned to the damaged office and pulled out essential files -- even those that were yellowed and moldy, Mr. Davis says. "We pick ourselves up and we move on and keep doing what we know how to do," he says.
Mr. Davis recounts a humbling moment when he called Judge Fallon to tell him: "Judge, I'm not going to be able to file that brief today. I don't even have a stapler." Mr. Davis says he and Judge Fallon laughed about the predicament.

How a law firm races to repair its Vioxx files

2006-02-17T06:44:00.000-08:00

How a law firm races to repair its Vioxx files
Wednesday, February 15, 2006By Heather Won Tesoriero, The Wall Street Journal
Hurricane Katrina destroyed a lot of things, but some of the most difficult to replace are legal files.
That is the dilemma facing the New Orleans law firm of Herman, Herman, Katz & Cotlar. The firm oversees a repository for 10 million documents relating to federal litigation of Merck & Co.'s painkiller drug Vioxx -- including medical reports, depositions and emails -- that plaintiffs' lawyers are permitted to use. Those documents were housed on the 43rd floor of an unharmed office building during the hurricane and stayed dry.
But many of Herman's own 125 federal Vioxx cases were waterlogged, and the firm is scrambling to recreate those documents to meet a court deadline Thursday to turn over files for 90 of those cases to Merck's defense team. That means using a private investigator to track down many plaintiffs whose homes were destroyed, and for whom litigation is the last thing on their minds.
A typical response from plaintiffs once they are found: "'I hadn't even thought about that. I've been busy trying to get things like shoes,'" recalls private investigator Anthony Valenti, a 67-year-old retired police officer.
The law firm is operating with half of its 65-person staff since it returned to temporary offices in the Big Easy in early January. Several employees lost everything, including Leonard Davis, a partner at the firm, and his paralegal.
"We're having a hell of a time," says partner Russ Herman. "We've got medical records destroyed at three hospitals that don't exist anymore."
Merck withdrew Vioxx from the market in Sept. 2004 after it was linked to an increased risk of heart attacks and strokes. The Whitehouse Station, N.J., drug giant faces 9,650 Vioxx cases in state and federal courts.
Katrina has caused other serious problems for the 4,350 federal cases consolidated under U.S. District Court Judge Eldon E. Fallon in New Orleans. The first federal Vioxx trial was relocated to Houston after the hurricane, and ended in a mistrial in December. The retrial started in New Orleans on Feb. 6.
The Herman firm plays a critical role in the federal Vioxx litigation at large. It was appointed by Judge Fallon to serve as an intermediary between the court and plaintiffs' attorneys around the country.
After the storm, the Louisiana governor extended the deadline for filing a case. After that, lawyers have 75 days to turn over files that include questionnaires filled out by plaintiffs and their medical records. The deadline for the Herman firm to submit completed forms to Merck is Thursday -- otherwise, Merck can ask the court to dismiss the cases. Merck liaison counsel Phil Wittmann says Merck has "routinely granted extensions to Mr. Herman and other Louisiana counsel in cases where they've had trouble completing the forms due to Katrina....If Mr. Herman calls me and explains what his problem is, we will grant his extension."
Following the storm, Herman sent letters to clients asking them to send information on their new locations. Almost no one responded. Mr. Valenti started tracking them down using credit card numbers, motor vehicle records and cellphone numbers. He located one plaintiff by obtaining the name of the man's auto insurer from motor vehicle records. The client had been in a car accident and was found living in Brookhaven, Miss.
Since many doctors' and hospitals' records were destroyed in the storm, Herman has been reaching out to third party companies that archive medical records, and even photocopy companies to see if they have them.
Mr. Herman says he is frustrated that he's been unable to locate Allen Rosenzweig, his jury consultant. Mr. Herman told Mr. Valenti, the private investigator, that Mr. Rosenzweig's father was a tailor named Murphy and his mother was named Florence, and he joked that the jury consultant "was crazy enough to be on the top of a roof someplace." Mr. Valenti, the private investigator, came up with a post office box in Kenner, La., and a phone number. The voice on the answering machine said it was Mr. Rosenzweig, but the jury consultant still hasn't been found.
A week after the storm, Herman staffers returned to the damaged office and pulled out essential files -- even those that were yellowed and moldy, Mr. Davis says. "We pick ourselves up and we move on and keep doing what we know how to do," he says.
Mr. Davis recounts a humbling moment when he called Judge Fallon to tell him: "Judge, I'm not going to be able to file that brief today. I don't even have a stapler." Mr. Davis says he and Judge Fallon laughed about the predicament.

Merck's first witness testifies in Vioxx trial

2006-02-17T06:43:00.000-08:00

NEW ORLEANS Merck began its defense of its once-popular pain reliever Vioxx in a New Orleans courtroom yesterday, discussing internal studies that suggested the drug would not cause heart trouble.Merck research doctor Briggs Morrison said while Vioxx seemed to reduce an enzyme that keeps blood flowing, Merck studies on rabbits injected with Vioxx showed that enzyme was not present in blood vessels, and therefore would not lead to heart attacks.
Testimony will continue today in first federal Vioxx lawsuit, after an earlier trial over the death of Floridian Richard "Dickie" Irvin ended in a hung jury.
Irvin's widow claims Merck rushed Vioxx to market and hid its dangers from the public.
Merck says Irvin had a history of cardiac trouble.

Scientists cross-examined in Vioxx retrial

2006-02-17T06:40:00.000-08:00

Using a big black, red and yellow chart labeled "Merck Knew But No Warning" to emphasize his points, a plaintiff's attorney cross-examined a top scientific executive for the drug company Thursday, as the first federal Vioxx trial neared its second closing.
U.S. District Judge Eldon E. Fallon, who is retrying a case that ended with a hung jury, told jurors that attorneys hoped to wind up evidence Thursday. In this case, Evelyn Irvin Plunkett contends that taking the drug for a month caused the heart attack which killed her husband Richard "Dickie" Irvin in May 2001, and that manufacturer Merck & Co. hid the drug's dangers.
For nearly four hours, Andy Birchfield asked Alise Reicin, vice president of clinical research at Merck, about two studies in which patients taking Vioxx had more heart attacks than those in comparison groups, and about related events.

The first study, called VIGOR, was reported to the U.S. Food and Drug Administration in 2000, but the heart attack information was not added to the Vioxx label until 2002. The second study, called APPROVe, prompted Merck to pull the drug from the market in September 2004.
The New England Journal of Medicine criticized VIGOR's authors in an editorial published online the day that the first jury began deliberations, saying they failed to mention three heart attacks among patients who were taking Vioxx.
Reicin said the company did report them to the FDA, but didn't feel it had to tell the journal because they didn't significantly change the results. With either set of figures, she said, rounding would have made the "relative risk" figure the same.
The figures reported to the journal were 17 heart attacks among patients on Vioxx and four among those taking another drug, called naproxen, or 4 1/4 times as many. The additional three changed that to 20 and four, or five times as many.
Merck, saying that the difference was probably because naproxen kept blood clots from forming, framed it as a reduction in the likely risk. Rounding off made that the same in either case, Reicin said: "a fivefold difference."
"And we highlighted those results in that paper," she said.
In earlier videotaped testimony, the journal's executive editor, Dr. Gregory Curfman, said the numeric difference was of great interest to the journal and its readers, and should have been reported to keep the article up to date.
"You withheld these three myocardial infarctions from the New England Journal of Medicine," Birchfield said.
That was "mischaracterization," Reicin said.
"You never gave it to them," Birchfield said.
That was because the earlier analysis already showed a significant difference, Reicin said. "Had these changed the conclusions, I think we would have thought differently about it. But it didn't change the conclusions."
She also repeated Merck's contention that it asked the FDA that year to approve a new label, but the approval process took two years.
A plaintiff's expert testified earlier that a label's warning can be strengthened without getting approval first from the FDA. Reicin said she wasn't aware of that.

Industry Insider: Merck takes the offensive to lay civility ground rules

2006-02-17T06:39:00.000-08:00

Merck sure picked a funny way to ask that its opponents observe rules of civility in an upcoming Vioxx trial in Atlantic City.
In a motion filed earlier this month, the drugmaker slagged Houston attorney Mark Lanier's conduct last summer during the Ernst trial in Texas, the first Vioxx case to go to a jury. Lanier won a $253.4 million judgment against Merck, although that amount is expected to fall to $26 million on appeal.
He will be lead attorney again in a dual trial in New Jersey Superior Court involving plaintiffs Thomas Cona and Robert McDarby, which is scheduled to begin early next month.
In its brief, Merck listed 14 "infractions" by Lanier in the earlier trial. The alleged sins included arguing with witnesses, offering personal views on the truthfulness of certain witnesses and references to Lanier's out-of-court roles as a part-time preacher and family man.
The pharmaceutical company's defense team also cited a recent ruling by U.S. District Court Judge Eldon Fallon, who is overseeing federal Vioxx cases, that denied the live playback of a deposition Lanier took. "It's just the tone and the smirking and the laughter that has no place in federal court," the judge said.
Merck attorneys seemed to recognize that pummeling an opponent preemptively was an odd way to promote rules of decorum. In their motion to Superior Court Judge Carol Higbee, they offered "apologies for the undesired (but, Merck believes, necessary) itemization of infractions."
For his part, Lanier said he could have filed similar citations on the behavior of Diane Sullivan, one of Merck's co-counsels in a Vioxx case brought by Frederick Humeston, which the drugmaker won in Atlantic City last fall. Sullivan clashed with Higbee several times, and once with a member of her own legal team.
"Merck doesn't need to worry, because I'm going to conduct myself within the rules of the court," Lanier said in a phone interview. "Different judges have different rules."
-- Jeff May
Who let the dogs in? In a victory for animal rights activists, the Securities and Exchange Commission ruled this week that Pfizer must allow a vote on an animal testing resolution at its stockholder meeting this spring.
People for Ethical Treatment of Animals has asked Pfizer to adopt resolutions that call for stepped-up protections for animals used in laboratory testing. Pfizer asked the SEC to declare the resolution ineligible for consideration.
"We're thrilled that the SEC agreed that shareholders have a right to vote on this issue," said PETA's director of regulatory testing, Jessica Sandler.
Over the past year, PETA has used shareholder meetings as a protest forum. Its resolutions typically lose by wide margins, but the group is happy just to get its issues before shareholders and the media.
In a letter to the SEC, Pfizer said PETA's request was "vague and indefinite" and that "the animals cannot communicate to Pfizer" that their "psychological, social and behavioral needs be met."
-- George E. Jordan

New pain relievers boost blood pressure more

2006-02-17T06:38:00.000-08:00

ISLAMABAD: Arthritis drugs known as COX-2 inhibitors raise blood pressure more than older pain relievers, which may explain why the newer medicines have been linked to heart attacks, Australian researchers reported.
The increases were small and varied among the different COX-2 drugs. The risk seemed highest with Merck & Co. Inc.’s Vioxx, the researchers said after reviewing data from more than 45,000 people in 19 studies. Merck pulled Vioxx from the market last September.
The study was published online on Monday by the Archives of Internal Medicine.
The safety of pain relievers is under scrutiny from regulators. A U.S. advisory committee will review the medicines at a three-day meeting starting on Wednesday.
The Archives of Internal Medicine said it released the findings early because they were relevant to the meeting.
One of the authors of the new study, Henry Krum, said the blood pressure increases seen with the COX-2 drugs were small, but they may be enough to help spur heart attacks.
"One could draw the conclusion the elevations in blood pressure are contributing to the increase in cardiovascular risk," said Krum, director of the National Health and Medical Research Council of Australia’s Center of Clinical Research Excellence in Therapeutics.
Some COX-2 inhibitors, as well as older pain relievers called nonsteroidal anti-inflammatory drugs or NSAIDs, had already been linked to higher blood pressure.
The new study was designed to determine if the widely used COX-2 drugs raised blood pressure more than NSAIDs such as ibuprofen and naproxen. The COX-2 drugs studied were Merck’s Vioxx and Arcoxia and Pfizer Inc.’s Celebrex.
On average, systolic blood pressure -- the upper number of a blood pressure measurement -- was 2.83 millimeters of mercury higher with COX-2 inhibitors than with NSAIDs. Diastolic pressure -- the lower number -- was 1.34 millimeters of mercury higher with the COX-2 drugs.
Vioxx "clearly is the most dramatic in elevating blood pressure," while Celebrex "looks pretty clean," Krum said.
The data on Arcoxia, which is approved in some countries but not the United States, were too limited to draw conclusions, Krum said.
Merck spokeswoman Casey Stavropoulos noted the study was an analysis of previously published research. "There will be a more complete review of selective COX-2 inhibitors and blood pressure at the (Food and Drug Administration) committee meeting later this week," she said.
COX-2 inhibitors were developed with the hope they would reduce pain as much as NSAIDs while being gentler on the stomach. NSAIDs can cause potentially fatal stomach and intestinal bleeding.
Only Vioxx has been shown to produce fewer serious gastric problems than NSAIDs. Vioxx was pulled after a study showed the drug doubled heart attack and stroke risk in patients who took it for at least 18 months.
"Clinicians need to weigh the risks of improved gastrointestinal safety versus potential hazards of developing elevated blood pressure when considering the use of these agents, especially in the elderly population," Krum and his colleagues wrote.
The research was funded by grants from Australia’s National Health and Medical Research Council and the Royal Australasian College of Physicians.
Krum has received consulting fees from Pfizer, Merck and Novartis -- all makers of COX-2 inhibitors. Another of the study’s authors was a consultant to Pfizer.

RIAA et al. says CD ripping, backups not fair use

2006-02-17T06:37:00.000-08:00

If anyone has any doubts about the content industry's resolve to destroy fair use and usher in new ways of charging you for uses that were previously both free and fair, look no further. As part of the triennial review of the effectiveness of the DMCA, a number of content-related industries have filed a joint reply (PDF) with the government on the effectiveness of the DMCA and the challenges that lay ahead for copyright. As you might expect, the document is a celebration of the DMCA, and the industries are pushing for even more egregious abuses of technology to fatten up their bottom lines.
With regards to the argument that the DMCA is bad law because it prevents users from making backups, the joint reply dismissed such arguments as "uncompelling." First, they argue that there is no evidence that "any of the relevant media are 'unusually subject to damage in the ordinary course of their use.'" This "cart-before-the-horse" argument suggests that people do not need to backup anything that does not have a high failure rate—a view that fundamentally misunderstands the purpose of backups. Furthermore, they argue that the success of DVD sales vis-à-vis VHS demonstrates that whatever problem there might be, it's not big enough to matter to consumers, because DVD sales are skyrocketing while VHS isn't. Thus high sales volumes are indicators that the consumer are well served, which is an argument that we'll hope never takes hold in the pharmaceutical industry (Vioxx sure did sell well!).
Such are the lengths they will go through in order to keep the anti-circumvention provisions of the DMCA intact. But supporting the status quo isn't in their interest. No, the idea is to embrace and extend. To wit, the joint reply also argues that making backups of your CDs is also not fair use.
The [submitted arguments in favor of granting exemptions to the DMCA] provide no arguments or legal authority that making back up copies of CDs is a noninfringing use. In addition, the submissions provide no evidence that access controls are currently preventing them from making back up copies of CDs or that they are likely to do so in the future. Myriad online downloading services are available and offer varying types of digital rights management alternatives. For example, the Apple FairPlay technology allows users to make a limited number of copies for personal use. Presumably, consumers concerned with the ability to make back up copies would choose to purchase music from a service that allowed such copying. Even if CDs do become damaged, replacements are readily available at affordable prices. Similar to the motion picture industry, the recording industry has faced, in online piracy, a direct attack on its ability to enjoy its copyrights. (emphasis added)
As you can see, the argument is hinged partially on the cost of replacements. Why should you be allowed to make backups of CDs you've purchased when you can replace them? And why should CD backups be legal when users can already decided to purchase from (DRM-laden) services that do allow the limited copying of lossy music files? Here, again, we see the way in which the RIAA et al. would like to see contract law take over the domain of fair use. "Leave it up to DRM, you big dummies!"
But they're not done with that argument. The real kicker is buried in a footnote, where the joint reply suggests the unthinkable: that making copies of CDs for any purpose may, in fact, be infringement.
Nor does the fact that permission to make a copy in particular circumstances is often or even "routinely" granted, see C6 at 8, necessarily establish that the copying is a fair use when the copyright owner withholds that authorization. In this regard, the statement attributed to counsel for copyright holders in the Grokster case, is simply a statement about authorization, not about fair use.
Allow me to translate: just because people have been copying CDs in the past doesn't mean that that they had the authorization to do so, and a general trend does not override such explicit authorization. But as the EFF has picked up, the RIAA is engaging in a little historical revision. Their last comment about the Grokster case is attempting to change the substance of comments that were uttered by their own legal counsel. Why they would do this is abundantly clear when you see the statement in question:
"The record companies, my clients, have said, for some time now, and it's been on their website for some time now, that it's perfectly lawful to take a CD that you've purchased, upload it onto your computer, put it onto your iPod."
It looks like someone is having a change of heart.
In the world of the joint reply, if and when the RIAA and its member studios say that copying your CDs is not permitted, then it's not permitted. Forget fair use. Forget historical precedent. The joint reply here is arguing that copyright owners have the authority to deny what has become fair use—what their own lawyers have admitted is fair use in front of the Supreme Court of the United States. The upshot is that this argument suggests that the most common form of CD "copying"—namely ripping CDs for use on computers and portable players—is not necessarily fair use. The joint reply adds:
Similarly, creating a back-up copy of a music CD is not a non-infringing use, for reasons similar to those the Register canvassed in detail in her 2003 determination that back-up copying of DVDs cannot be treated as noninfringing. [Ed note: see above arguments.] While we recognize that access controls may in some circumstances affect copying, the fact remains that there is no general exception to the reproduction right to allow back-up copying (except the limited exception in § 117 for computer programs) and thus no justification for allowing circumvention of access controls for this purpose.
Inasmuch as the joint reply was grafted in defense of the DMCA, it remains unclear if the RIAA has any plans to take up this line of argument in front of legislators or the public. It does mark, however, yet another development in the erosion of fair use, and it demonstrates that the insidious notion of "customary historic use" stems from part of the industry's campaign to legislate new business models that fly in the face of fair use, the doctrine of first sale, and limited copyrights.

Market return for Vioxx and Bextra?

2006-02-13T06:10:00.001-08:00

Will the scorned painkillers Vioxx and Bextra ever get back on the market? Will Celebrex ever shake its black box warning?
These arthritis drugs, produced by Merck and Pfizer, are all members of the same class, known as COX-2 selective non-steroidal anti-inflammatory drugs, or NSAIDs for short. The popular painkillers raked in billions of dollars for their makers before they ran into regulatory trouble, and the Food and Drug Administration is holding a meeting on Friday to glean more information on health risks.
The FDA isn't going to make any decisions on Friday about the fate of these drugs. But experts have been weighing the possibilities of an eventual market return for Merck's Vioxx and Pfizer's Bextra, and whether Pfizer's Celebrex will improve its status in the eyes of regulators.
The future of Vioxx
Analysts are mixed on the prospects for Vioxx:
"I'm not holding my breath, but I think there is a chance that Vioxx could come back," said Jami Rubin, analyst for Morgan Stanley.
Rubin said the "huge body of data" about the risk profile concerning Vioxx could be used to bring the drug back into the fold. But David Moskowitz, analyst for Friedman, Billings & Ramsey, said that Vioxx will "certainly not" be brought back, because of a wealth of evidence pointing to the drug's cardiovascular risks.
"The product seemed to cause high blood pressure compared to the other drugs, and Vioxx would be implicated as the more dangerous product [compared to other NSAIDs,]" said Moskowitz.
When asked about a Vioxx market return, Robert Hazlett, analyst for Suntrust Robinson Humphrey, said, "There is a chance that could occur. It is an outside chance, but there is a chance."
The NSAID trouble began with Merck's (down $0.42 to $33.92, Research) Vioxx, which totaled $2.5 billion sales in 2003, its last full year on the market. Merck, based in Whitehouse Station, N.J., pulled the drug off the market in September, 2004, after a study showed increased risk of heart attacks and strokes in patients taking the drug for at least 18 months. Since then, nearly 10,000 lawsuits have been filed against Merck by plaintiffs who blame the drug for heart attacks, fatal and non-fatal. So far, Merck has lost one case, won two, is retrying another case that ended in a hung jury, and has another case ongoing.
The future of Bextra
The trouble for Pfizer (down $0.62 to $25.72, Research) came to light a few months later, in April of 2005, when the FDA asked the New York-based drug giant to take Bextra, which totaled $1.3 billion in 2004 sales, off the market. Pfizer's Celebrex remains on the market to this day, but sales have been cut in half, to $1.7 billion in 2005 from $3.3 billion in 2004. In July of 2005, the FDA had Pfizer add a "black box," the most severe type of warning, to its Celebrex label to reflect risks of heart attacks, strokes and gastrointestinal bleeding.
Analysts weren't so rosy about a market return for Bextra. While Vioxx has a wealth of data, positive and negative, Bextra does not, so Pfizer would have to invest in expensive studies to demonstrate the drug's safety to regulators.
"Pfizer would have to run more clinical studies for [Bextra's return to market,] and the market has really shrunk to the point where it's doubtful that Pfizer would ever return the product to market," said Moskowitz of FBR.
The future of Celebrex
Celebrex remains on the market with a black box that warns of possibly fatal heart attacks, strokes and gastrointestinal bleeding. Analysts are mixed as to whether the warning is a permanent or temporary.
Rubin of Morgan Stanley said that not only will Celebrex always have that black box, but that someday all NSAIDs will carry it, including the over-the-counter ibuprofen. But Moskowitz of FBR believes that Pfizer might shake the warning by tapping its wealth of safety data concerning Celebrex, particularly with regard to the gastrointestinal risks.
Dr. Eric Matteson, NSAID expert and professor of medicine at the Mayo Clinic College of Medicine in Rochester, Minn., said that of all the major NSAIDs, Celebrex is definitely the safest and the only one that should still be available for patients.
"The concerns that led to Vioxx and Bextra being pulled from the market are grave concerns," said Matteson. "In my opinion, Celebrex is still on the market because the degree of cardiovascular events from Celebrex is not as high as Bextra and Vioxx. A drug like Celebrex is in a good position to remain on the market."
Dr. Mark Fendrick, NSAID expert and professor of internal medicine at the University of Michigan, said that Vioxx, Bextra and Celebrex were initially developed as alternatives to other NSAIDs like ibuprofen because they're easier, or intended to be easier, on the stomach. He said this fact is often overlooked amid the hype surrounding the fallen-from-grace blockbusters.
"If you have gastro-intestinal concerns, and you don't have heart concerns, and you're not taking aspirin, then that's where COX-2 inhibitors – Vioxx, Bextra, Celebrex – have a safety advantage," said Fendrick. "I do believe that in the absence of aspirin, Celebrex is safer for those with gastro-intestinal risk. They're no better in terms of pain relief, but they have an advantage for gastro-intestinal safety. If only we gave them to people to get the gastro-intestinal advantage, we wouldn't have this trouble."
To read about a study on NSAIDs and heart disease, click here.

The Merck Vioxx Litigation: Pathological Scouting

2006-02-13T06:10:00.000-08:00

Here’s another dispatch filed by WSJ reporter Heather Won Tesoriero from the federal Vioxx retrial in New Orleans:
The issue of whether Merck & Co.’s troubled painkiller caused the 2001 fatal heart attack of Richard “Dicky” Irvin could come down to a battle of the pathologists. And it seems Merck isn’t taking any chances: while the plaintiff’s expert pathologist Michael Alan Graham took the stand, Thomas Wheeler, a pathologist who is likely to testify for Merck next week, sat in the gallery, taking notes and appearing to size up his opponent. There was a even a “small world” professional nod, with Graham acknowledging that he’s known Wheeler since his residency and that “he’s a good pathologist.” Wheeler testified on Merck’s behalf in the first federal trial in December.
Graham explained to jurors the mechanics of Irvin’s heart attack. Using large-scale slides from the deceased’s autopsy, Graham testified that Irvin had a plaque rupture in an artery which led to a fatal, heart-attack-producing clot. But Judge Eldon E. Fallon put strict limits on Graham’s testimony, ruling that while the doctor could testify about the presence of a clot and whether the clot killed Mr. Irvin, Graham was barred from linking Vioxx to that clot. Judge Fallon wrote that Graham lacked the qualification or preparation to offer an opinion on Vioxx’s role:
To compensate for his lack of education, experience and training, Dr. Graham spent approximately eight hours reviewing sixty-seven scientific medical articles, nine depositions, four expert reports, and three days’ worth of trial transcripts—far less than this Court or any attorney in this case has spent reviewing Vioxx related materials . . . While the Court could further explain Dr. Graham’s lack of qualifications or his lack of a reliable scientific basis, it is enough to say that he is not qualified to render an opinion as to whether Vioxx can cause a thrombotic cardiovascular event or whether Vioxx did cause Mr. Irvin’s death.
Ouch. Still, on the stand, Graham went as far as to say that it was unlikely that Irvin would’ve died absent a catalyst, though, sticking to the Judge’s ruling, no catalyst was named.
Dr. Wheeler was on a 5:30 p.m. Continental flight back to Houston, where he’s based. When asked about his appearance in court earlier in the day, he smiled and said, “I was just watching

Key Vioxx critic leaving clinic

2006-02-13T06:09:00.000-08:00

Dr. Eric Topol, a world-renowned cardiologist who has taken on drug advertising and pharmaceutical companies but has faced questions about his own potential conflicts of interest, is leaving the Cleveland Clinic.

Topol — who attacked the pain reliever Vioxx while working as a consultant for a hedge fund that was betting against the drug's manufacturer — will become a genetics professor at Case Western Reserve University, the school announced Thursday. Topol has been a Case medical professor.
"We're delighted to strengthen our ties with Eric in the work we do," Case medical dean Dr. Ralph Horwitz said.
Neither Topol nor the clinic immediately responded to requests for comment.
Topol, 51, has led the Cleveland Clinic's distinguished cardiology program for 14 years and is known for his work on the role of genetics in heart disease. He used the clinic's prestige to raise awareness of heart disease.
Topol was one of the first scientists to raise doubts about the safety of Vioxx, and has been a key witness in lawsuits arguing that Merck & Co. concealed the dangers.
Topol also has criticized the $500-per-dose cost of the popular heart medication Natrecor and charged that is being given unnecessarily to some patients. He has also complained that advertisements by drug companies glamorize medicines.
In December, Topol lost two high-profile positions at the clinic when the medical school he helped establish there eliminated his dual position of provost and chief academic officer.
His departure comes as the Cleveland Clinic confronts questions about ethical conflicts between patient needs and profits among researchers such as Topol and Chief Executive Toby Cosgrove.
In December, a Wall Street Journal article detailed Cosgrove's relationship with AtriCure, a medical device company, and the clinic's role in a venture capital firm that invested in it. Cosgrove sat on AtriCure's board and served as a general partner.
The clinic announced Thursday it was tightening its ethics policies after a preliminary review found that poor disclosure practices by Cosgrove reflected problems throughout the clinic. Clinic spokeswoman Eileen Sheil said the clinic must correct the "imbalance between innovation and transparency."
Topol has said that he was unaware when he was working as a paid consultant to the hedge fund that was short-selling. He said that he had no financial interest in the fund and that he quit the work.
Merck pulled Vioxx from the market after its own study showed that the drug doubled the risk of heart attacks and strokes.

FDA: Merck Had Time to Warn About Vioxx

2006-02-13T06:08:00.000-08:00

Merck & Co. could have warned that its popular painkiller Vioxx might increase the risk of heart attacks as soon as the first evidence showed up, rather than waiting two years for federal approval, a former Food and Drug Administration official testified Friday.

Richard Kapit said there was plenty of time to alert the public before Richard "Dickie" Irvin began taking Vioxx, which his widow claims caused his fatal heart attack after a month on the drug in 2001.
Merck says it alerted the FDA in 2000 that a study showed heart attacks occurred five times as often in patients taking Vioxx as those on another drug, called naproxen. The agency didn't approve the label change until April 2002.
The company pulled the drug from the market in September 2004, after another study showed that it could double the risk of heart attacks.
Kapit, who worked for the FDA for 16 years, mostly as a drug application reviewer analyzing adverse effects, said companies are allowed to change a drug label as soon as it applies for permission to add or strengthen a warning, precaution, or other information about a serious side effect.
"The FDA is a bureaucracy ... you don't want to wait until it goes through all the records," he said.
He said he saw hundreds of such applications during his years at the FDA, which he left in 2002. He did not work on Merck's application for Vioxx.
Under cross-examination, he said he based his analysis on about 80 pages of documents supplied by the plaintiff and his knowledge of FDA regulations.
The New England Journal of Medicine's Executive Editor, Dr. Gregory Curfman, also testified in a videotaped deposition played for the jury Friday, saying the information about the drug's effects should have been added to an article about the drug before it was published.
Merck contends it learned the information about heart attacks, which occurred after a reporting deadline set in the study. Curfman said scientific journals expect important updates.
More of Curfman's deposition will be played when the trial resumes Monday. Testimony is expected to last most of the week, with closing arguments expected Friday.
The initial case ended in a mistrial last year.

Plaintiffs Lawyer Proposes Pay Hike for Vioxx Jurors

2006-02-10T06:28:00.001-08:00

As New Jersey's next, predictably lengthy Vioxx trial approaches this month in Atlantic City, a lawyer for the plaintiffs is proposing a way to make jury service more palatable: supplemental juror pay.
He's not talking about a slight bump up of the $40 per diem maximum rate, either. Instead, he'd like to boost it to $100, with the excess funded equally by the plaintiffs and defendant Merck & Co.
The idea is unheard of in New Jersey, but you can't blame W. Mark Lanier for trying. He proposed the same plan last summer in Angleton, Texas, and the well-paid jury, after a six-week trial, awarded $253.5 million to a Vioxx user's widow.
Texas has a statute allowing such excess funding: New Jersey does not. So Lanier's request, at a Jan. 25 conference with Atlantic County Superior Court Judge Carol Higbee, blazes a new trail. At issue is the makeup of the jury for a trial that begins on Feb. 27 and is expected to last six weeks. The plaintiffs suffered heart attacks after protracted Vioxx use.
Higbee is keeping an open mind. If she approves the plan, and if Merck goes for it, jurors would receive weekly cashier's checks, in addition to their court pay, without knowing the source.
The idea behind the plan is to get a more representative jury pool, since the added compensation would quell blue-collar workers' most common objection to lengthy jury service: loss of income.
In Atlantic City, casinos do not provide long-term payment for jury service, and "that cuts off a majority of the population" from service, says plaintiffs lawyer Samuel Davis of Teaneck's Davis Saperstein & Salomon. "What you're doing is precluding juror diversity."
There seems little in it for Merck, which won a startling no-cause verdict last November after a seven-week Vioxx trial with a white-collar jury: eight of the nine jurors were white, middle-class professionals, including a doctor's wife and schoolteacher, a bank manager and a county prosecutor. The one casino worker, a Honduran immigrant, was the only juror to find for the plaintiff on any issue.
Thus, Merck's lawyers were tepid about the plan, according to three plaintiffs lawyers at the conference. Merck spokeswoman Casey Stavropoulos declined to comment. Theodore Mayer of New York's Hughes Hubbard & Reed, who orchestrates Merck's Vioxx trial strategy, did not return a call.
'TWO-TIER SYSTEM' FEARED
The idea of supplementing jurors' stipends doesn't sit well with former N.J. jurists interviewed. "You can't change the rules of the game for one litigant," says former state Supreme Court Justice Daniel O'Hern. "It would create a two-tier system of justice," wherein litigants' fortunes would depend on their financial resources.
But other states besides Texas have enacted fee-financed programs to enhance juror pay during lengthy trials.
Minnesota passed legislation to pay jurors financially harmed by long service, inspired by losses suffered by jurors who served in a four-month tobacco trial in 1998 that ended in a $7.1 billion settlement. One juror lost his house to foreclosure, another nearly lost his job and a third was forced into bankruptcy, according to Paula Hannaford-Agor, director of research at the National Center for State Courts in Williamsburg.
In Arizona, civil litigants are charged an additional $15 filing fee to fund supplemental pay (beyond the standard $12 per diem) in trials that last longer than 10 days. Unemployed jurors get $40 a day, from the fourth day to the end; employed jurors not receiving their usual income get up to $100 a day between the fourth and 10th day, and up to $300 a day thereafter. Jurors whose employers pay for their service receive no stipend. The program is based on a model by the American Legislative Exchange Council, which seeks to improve jury service.
In the first 18 months of the program's operation, ending last June, Arizona provided about $130,000 in additional compensation to 172 jurors in 48 long trials, according to an article by G. Thomas Munsterman, director of the center for jury studies at the National Center for State Courts, and Cary Silverman of Shook, Hardy & Bacon in Washington, D.C. Their findings will be published this March in the American Bar Association's Judges' Journal.
Munsterman and Silverman say Arizona's program allowed service by low-wage workers, who otherwise would not have been financially able to sit.
Arizona legislators who opposed the program pointed to the inequity of varying payments to jurors serving on the same trial. But Arizona court administrators responded by saying that the fund remedies "an already unequal situation in which some jurors are paid by their employers during jury service while others are not," say Munsterman and Silverman.
Silverman says Vioxx cases are good examples of trials that require great financial sacrifice of jurors. "The Lengthy Trial Fund provides an innovative means to address this issue and ... has proven itself in Arizona," says Silverman. "Getting people from all walks of life to serve [on juries] is an issue that should have the support of both the plaintiff and defense bar... . While few trials last longer than three or four days, those that do have high stakes," he adds.

Doctor Critical of Vioxx Leaving Clinic

2006-02-10T06:28:00.000-08:00

Dr. Eric Topol, a world-renowned cardiologist who was one of the first scientists to raise doubts about the safety of the pain reliever Vioxx, will leave the Cleveland Clinic and its top-ranked heart center to teach at nearby Case Western Reserve University, the Case medical school announced Thursday. The hospital has been confronted with questions about ethical conflicts between patient needs and profits by its researchers, including Topol and CEO Toby Cosgrove, also a noted cardiac surgeon. Merck & Co. pulled the arthritis pain killer Vioxx from the market because its own study showed the drug doubled a patient's risk of heart attacks and strokes. It turned out that Topol was a paid consultant to a hedge fund that was betting against Merck shares. Topol said he was unaware of the short-selling, had no financial interest in the fund and quit. The reason Topol is leaving the hospital was unclear. His departure from the clinic is imminent, said Dr. Ralph I. Horwitz, medical dean at Case Western Reserve University. Topol, 51, is known for his pioneering work on the role of genetics in heart disease, and he used the clinic's premier standing to crusade for awareness of the number one health threat to people's lives. He has been a medical professor at Case. His new appointment as a professor of genetics will involve teaching and research, Horwitz said. Messages seeking comment were left for Topol and the hospital. Topol has directed the clinic's cardiology program for 14 years. His departure, first reported on The (Cleveland) Plain Dealer's Web site, caps more than a year of upheaval at the clinic, whose heart center under Topol's leadership has been ranked No. 1 nationally by U.S. News and World Report for 11 years. The center attracts patients from around the world. In December, Topol lost two high-profile positions at the clinic when the medical school he helped establish decided to eliminate the dual position of provost and chief academic officer. The Cleveland Clinic Lerner College of Medicine of Case Western Reserve University opened in 2004. Topol will be teaching both Case and Lerner college medical students in his new position, Horwitz said. "We're delighted to strengthen our ties with Eric in the work we do," Horwitz said. "Doctor Topol, I think, is one of the pre-eminent physician-scientists in the United States."

Hidden Data Haunting Computer Users

2006-02-10T06:27:00.000-08:00

When the New England Journal of Medicine used a word-processing function to reveal that Merck had deleted study data about Vioxx and heart attacks, the pharmaceutical giant joined a long line of organizations bitten by information lurking in electronic files.
It's happened to organizations from the Pentagon to the British prime minister's office.
Each time, making minor electronic adjustments to documents aired juicy details not meant for public disclosure -- such as the true author of a file or sensitive data hacked from a final draft.
The pitfalls of such hidden "metadata" have long been known in computer-savvy circles, but these high-profile leaks are driving new efforts to keep a lid on metadata. So sensitive is the topic for the U.S. government that the National Security Agency released guidance in December on how agencies can properly redact reports.
For the corporate world, several companies are finding success in selling tools to automatically scan for and remove metadata.
Metadata is data about data. A word-processing document, for instance, has metadata on who authored it, when someone saved it and what that person did to it. Microsoft's Word program has a "track changes" feature that preserves a file's original text and shows another person's edits. All that is metadata.
This information is designed to stick around because it can help people organize their files and collaborate with one another.
But because it doesn't show up when a document is printed and doesn't appear on screen in normal settings, it's easy to forget about.
Fears about the hazards of metadata led Microsoft to pull back on a planned feature in Vista, the upcoming Windows operating system. Originally, Vista was going to let users drag and drop files into spots on the desktop in order to label documents with personalized categories.
But Vista testers told Microsoft it might become "a little too easy" to apply the categories and have them stick permanently to the document, said Mike Burk, a Windows product manager. That could get ugly if a file labeled "projects I hate" were e-mailed to a boss.
Meanwhile, the next generation of Microsoft's widely used Office software, which includes Word, Excel and PowerPoint, will make it simpler to strip metadata from files before they are disseminated.
Even so, Gartner analyst Michael Silver says the problem will remain -- metadata will exist in documents unless users make a point of getting rid of it.
"It's still a manual process. It's still something you have to remember to do," Silver said. "Any time you're relying on the user to remember something, there's a good chance that they'll forget."
The Pentagon had a hidden-data episode last May. Before posting a report in Adobe Systems' Portable Document Format about a U.S. soldier who had accidentally killed an Italian secret service agent in Iraq, officials covered up classified information with black bars.
But there's a difference between covering and deleting information. Readers simply uncloaked the text by cutting it from under the black and pasting it elsewhere.
Automated tools to help protect against metadata releases have existed for a while, but they are beginning to see wider use. For example, Workshare sells a product called Trace that scans documents for metadata and ranks the findings by risk level. For most of Workshare's six years in existence, the company's customers were primarily lawyers, who are particularly sensitive about client information escaping to the opposing side.
But in the past year, Workshare has seen business expand to 60 percent of the Fortune 1000, said CEO Joe Fantuzzi. Revenue has surpassed $25 million, and Fantuzzi believes metadata protection is on the verge of being a must-have for corporate technology buyers.
Richard Smith, a computer privacy expert at Boston Software Forensics, mined metadata to determine who in the British prime minister's office worked on a 2003 dossier on Iraq.
Even in a world more attuned to the perils of metadata, however, Smith doesn't think the material will dry up.
"There are simply too many people who work in governments around the world, and there is no way to educate them all about metadata," he wrote in an e-mail. "I expect to see a steady stream of slip-ups in the future."

Plaintiff attorneys change approach in first federal Vioxx case

2006-02-10T06:26:00.000-08:00

Lawyers switched legal tactics for the retrial of the first federal Vioxx case, working to convince jurors that manufacturer Merck & Co. ignored safety in favor of sales, rather than opening with medical testimony. That approach is much closer to an earlier trial in a Texas state court, in which jurors decided Whitehouse Station, N.J.-based Merck should pay $253.4 million, than to the original federal trial. The federal trial ended with a hung jury; jurors reached afterward said the deadlock was 8-1 in Merck's favor.
Evelyn Irvin Plunkett claims that taking Vioxx for a month caused the heart attack which killed her husband Richard "Dickie" Irvin in 2001, and that Merck hid the dangers of its product from scientists and the public. In the Texas trial, the first witnesses were physicians and pathologists who explained why they believed that Vioxx had caused the heart attack. Merck contends that the heart attack was caused by a 30-year buildup of plaque in his blood vessels and had no relation to Vioxx. This time, the first three witnesses all worked in Merck's marketing or public relations department. On Tuesday, off-camera attorneys questioned J. Martin Carroll, who was executive vice president of marketing in 2001, and Jan Weiner, executive director of public affairs, about why information about heart attacks wasn't part of marketing or press materials. "It's not a change of tactics," just a matter of bringing in evidence which became available after the first trial, said Russ Herman, head of the federal plaintiffs' steering committee and spokesman in this trial for Plunkett, said Monday. The first witness, whose testimony was played Monday afternoon, was asked about internal correspondence including a reference to a "bad guys list" of doctors who questioned the drug's safety, and a memo listing "physicians to neutralize." The "neutralize" list was among the first evidence brought up in the earlier state trial in Angleton, Texas. However, Herman said the legal team didn't have other documents to support their claim that Merck used "junk science." The e-mail nomination of a doctor to the "bad guys list" had been sent to Baumgartner. "That wasn't my phrase," she said. She said "neutralize" meant to provide correct information so those doctors would "come to a neutral or fair position," she said. In rebuttal testimony played for the jury Tuesday, she said she got a pharmacology doctorate to follow her father's footsteps, and worked for Merck because it embodied her values of putting patients first. Meetings which the plaintiff's attorney had characterized as attempts to change doctors' minds included physicians whose opinions crossed the spectrum, because the aim was to learn what they thought, she said. Merck did not put on any rebuttal video for Carroll or Weiner. It didn't need to because the witnesses were clear, spokesman Kent Jarrell said. "This case is all about causation. That is the most important part of the case," he said. "Marketing doesn't go to the point because the prescribing doctor never reviewed the literature and never met with marketing representatives" from Merck. Carroll, who now is president and chief operating officer of Boehringer Ingelheim Pharmaceuticals Inc., of Ridgefield, Conn., was shown several Merck studies in which patients taking Vioxx had more heart attacks and other cardiovascular problems than those given another drug or sugar pills. He said he hadn't seen them before. They were written while Carroll was at Merck, and its sales representatives had information cards saying Vioxx was about as safe for the heart as a sugar pill. "This says the trend is against Vioxx. Not similar. Right?" an off-camera attorney asked. "That's what it says," Carroll answered. A bit later, the attorney asked, "Did you share this information with doctors?" That wasn't information for salespeople _ they have to stick to what's on the label and packaging insert, Carroll said. Doctors have plenty of other information sources, such as medical conferences, meetings and publications, he said.

Jury seated in retrial of federal Vioxx case

2006-02-10T06:25:00.000-08:00

NEW ORLEANS – An eight-member jury was seated Monday for the retrial of a federal lawsuit over whether Vioxx caused the death of a Florida man and if the pain killer's manufacturer, Merck & Co., hid the drug's dangers.
Opening arguments were to begin Monday afternoon before the five-man, three woman jury. U.S. District Judge Eldon Fallon had told jury pool members that at least six people are required for a federal civil trial and he planned to seat eight for this one – a retrial of the first federal civil trial of a Vioxx lawsuit, which ended with a hung jury.
The first federal trial was held in Houston in the wake of Hurricane Katrina. Once again, jurors will be asked to decide whether Vioxx caused the death of Richard “Dicky” Irvin, who took the drug for about a month before suffering a fatal heart attack.
Merck withdrew Vioxx from the market in September 2004 after a study showed it doubled patients' risk of heart attack and strokes after 18 months of use. Around 9,650 Vioxx lawsuits has been filed against Merck. Aside from the hung jury, Merck has won one case and lost another. An additional case is going on in state court in Texas.
The court had sent out notices to 200 potential jurors. With 61 of them reporting to Fallon's courtroom, all available jury pool seats were filled.
Those dismissed included a man who said he couldn't give video testimony the same weight as testimony in person. “I don't trust people to start with, and I've been told all my life, 'Don't trust anything you see on TV.'”
The question whether prescription drug companies do a good job of monitoring safety of drugs once they are on the market prompted a diatribe from one man. “They don't care what happens once they're on the market,” he said. “You can have a judgment here, one there. The company still makes billions of dollars. They don't care.”
Merck shares were down 56 cents to $33.83 in afternoon trading on the New York Stock Exchange.

Cos., Gov't Seek to Keep Lid on Metadata

2006-02-06T06:30:00.000-08:00

BOSTON Feb 3, 2006 (AP)— When the New England Journal of Medicine used a word-processing function to reveal that Merck & Co. had deleted study data about Vioxx and heart attacks, the pharmaceutical giant joined a long line of organizations bitten by information lurking in electronic files.
It's happened to no less than the White House, the Pentagon, the British prime minister's office and the United Nations.
Each time, making minor electronic adjustments to documents aired juicy details not meant for public disclosure such as the true author of a file or sensitive data hacked from a final draft.
The pitfalls of such hidden "metadata" have been long known in computer-savvy circles, but these high-profile leaks are driving new efforts to keep a lid on metadata.
So sensitive is the topic for the U.S. government that the National Security Agency released guidance in December on how agencies can properly redact reports.
For the corporate world, several companies are finding success in selling tools to automatically scan for and remove metadata.
Metadata is data about data. A word-processing document, for instance, has metadata on who authored it, when someone saved it and what that person did to it. Microsoft Corp.'s Word has a "track changes" feature that preserves a file's original text and shows another person's edits. All that is metadata.
This information is designed to stick around because it can help people organize their files and collaborate with one another.
But because it doesn't show up when a document is printed and doesn't appear on screen in normal settings, it's easy to forget about.
In the Merck case, the company said the Vioxx data that was uncovered by the New England Journal had been deleted merely because the heart attacks in question came after a cutoff date for collecting information in the study.
Fears about the hazards of metadata led Microsoft to pull back on a planned feature in Vista, the upcoming Windows operating system. Originally, Vista was going to let users drag and drop files into certain spots on the desktop in order to label documents with personalized categories. Currently, grouping files by category is more laborious.
But Vista testers told Microsoft it might become "a little too easy" to apply the categories and have them stick permanently to the document, said Mike Burk, a Windows product manager. That could get ugly if a file categorized in "projects I hate" were e-mailed, say, to a boss.
Meanwhile, the next generation of Microsoft's widely used Office software, which includes Word, Excel and PowerPoint, will make it simpler to strip metadata from files before they are disseminated.
Even so, Gartner Inc. analyst Michael Silver says the problem will remain metadata will exist in documents unless users make a point of getting rid of it.
"It's still a manual process. It's still something you have to remember to do," Silver said. "Any time you're relying on the user to remember something, there's a good chance that they'll forget."
And so it wasn't surprising that when the White House posted a policy paper about strategy in Iraq last year, a quick command revealed the author. What was significant was that it was penned outside the administration, by Duke University political scientist Peter Feaver, a National Security Council adviser.
Earlier, a United Nations report on the assassination of former Lebanese Prime Minster Rafik Hariri developed new layers of intrigue when it was revealed that damaging accusations about Syria's involvement had been removed before publication.
The NSA's December paper ("Redacting with Confidence: How to Safely Publish Sanitized Reports Converted from Word to PDF") could have helped the Pentagon prevent its hidden-data episode last May.
Before posting a report in Adobe Systems Inc.'s Portable Document Format about a U.S. soldier who had accidentally killed an Italian secret service agent in Iraq, officials covered up classified information with black bars. But there's a difference between covering and deleting information. Readers simply uncloaked the text by cutting it from under the black and pasting it elsewhere.
Automated tools to help protect against metadata releases have existed for a while, but they are beginning to see wider use.
For example, Workshare Inc. sells a product called Trace (a free version can be downloaded) that scans documents for metadata and ranks the findings by risk level. One way a high risk is assigned is when a document lists all its authors and storage locations, because such data can guide hackers.
For most of Workshare's six years in existence, the company's customers were primarily lawyers, who are particularly sensitive about client information escaping to the opposing side.
But in the past year, Workshare has seen business expand to 60 percent of the Fortune 1000, said CEO Joe Fantuzzi. Revenue has surpassed $25 million, and Fantuzzi believes metadata protection is on the verge of being a must-have for corporate technology buyers.
"I think it could just break out, just like antivirus," he said.
Unlike antivirus protection, however, the tools to strip metadata from documents rest in everyday users' hands. Microsoft has long made it possible for users to erase telling metadata before documents are disseminated. The problem is that the steps are often cumbersome or obscure.
Microsoft hopes to resolve that in part by adding a metadata scan as a "file" menu option in Office programs. And a tweak in Vista could help.
Despite having yanked the drag-and-drop metadata tool, Microsoft is adding new labeling functions to Vista, including an ability to slap comments and a rating of one to five stars on documents. The twist is that the box that will facilitate this will also include an option for erasing the information.
"We've worked really hard to find a middle ground," Burk said. "We feel like we've got a good kind of solution that gives customers the benefit of metadata without exposing them to too much risk."
Gartner's Silver suggests that Microsoft could go further, by upgrading its Exchange e-mail server software to let companies automatically strip metadata from documents before they are e-mailed or posted online a trick offered by third-party metadata protectors.
Burk said Microsoft might consider it.
Of course, wider use of metadata-scanning tools will reduce the juicy finds that have benefited journalists and others.
Richard M. Smith, a computer privacy expert at Boston Software Forensics, mined metadata to determine who in the British prime minister's office worked on a 2003 dossier on Iraq. He also has picked up clues about the provenance of video clips on al-Qaida-related Web sites.
Even in a world more attuned to the perils of metadata, however, Smith doesn't think the material will dry up.
"There are simply too many people who work in governments around the world and there is no way to educate them all about metadata," he wrote in an e-mail. "I expect to see a steady stream of slip-ups in the future."

Ex-Merck Exec to Testify at Vioxx Trial

2006-02-06T06:29:00.000-08:00

NEW YORK - Former Merck & Co. Chairman and Chief Executive Raymond Gilmartin has agreed to a plaintiff lawyers‘ request that he testify at a Vioxx trial slated to begin in Atlantic City in late February, both sides said.
Gilmartin has given testimony in videotaped depositions, but Lanier said that it is always better to have a live witness than a tape. He called the depositions "canned speeches" and said it is harder for witnesses to give soliloquies or avoid questions in the presence of a judge.
A Merck official said the company believes Gilmartin will be a strong witness, noting his performance in front of a Senate committee hearing in late 2004, when he answered questions about the withdrawal of the pain reliever in September 2004. The drug was taken off the market after a study showed it doubled patients‘ risk of heart attacks and strokes when taken for longer than 18 months.
"Mr. Gilmartin has a good story to tell about Merck‘s responsible actions concerning Vioxx and the voluntary withdrawal of the product," said Kent Jarrell, a Merck spokesman.
Merck also announced it had sent aside an additional $295 million for litigation expenses bringing the total amount it has earmarked for legal costs to $970 million. However, the company said it spent $285 million on defense costs last year, leaving it with $685 million, which it believes will last through 2007.
The upcoming trial in New Jersey is slated to combine two plaintiffs, each a man who suffered a nonfatal heart attack after taking Vioxx for more than 18 months. Lanier represents one of the men.

Judge: Doctor Can't Testify in Vioxx Case

2006-02-06T06:26:00.000-08:00

NEW ORLEANS — A physician called to testify that Vioxx caused a blood clot which killed a Florida man cannot do so, the judge in the first federal Vioxx lawsuit ruled Friday.
That appears to cut to the heart of Evelyn Irvin Plunkett's claim against manufacturer Merck & Co. in the death of her husband, Richard "Dickie" Irvin, who took the drug for a month.
Her attorneys had called Dr. Michael Graham as an expert to say that Vioxx could cause blood clots in that short a time and had caused the one that brought on Irvin's fatal heart attack in 2001.
But U.S. District Judge Eldon E. Fallon ruled late Friday that Graham wasn't qualified to do that. He wrote that the doctor has no pharmacology training, isn't qualified to explain how Vioxx might cause a blood clot, has never prescribed it, and got most of his knowledge about the drug in an eight-hour review of medical articles, expert reports and trial transcripts.
"Dr. Graham is qualified to testify as to the existence of a thrombus and its role in Mr. Irvin's death. He is just not qualified to testify that Vioxx can cause a thrombus and did cause Mr. Irvin's thrombus," Fallon wrote.
Attorneys in the case have been told not to talk to reporters about it.
Merck spokesman Kent Jarrell said Fallon's order speaks for itself.
Merck's motion seeking Graham's disqualification said Plunkett apparently has dropped the three medical experts who testified in the first trial, held in Houston because of Hurricane Katrina.
Plunkett claims that Vioxx caused the blood clot by tamping down an enzyme that would otherwise thin the blood and prevent clots.
Although Fallon has told attorneys he wants to try to work out a settlement after the first four federal Vioxx trials, he also has set up a plan that could bring more cases for early trial.
The next two are scheduled in May and June.
By Feb. 15, attorneys for Merck and for the plaintiffs' steering committee are to draw up two lists of five cases for early trial, Fallon wrote in an entry filed on Friday. One list will be of Louisiana cases, the other of cases filed in federal courts outside Louisiana. Each side can eliminate two cases from the other side's list.
Fallon will choose from the remaining cases.

Medical Journal's article is a wild card in federal Vioxx retrial

2006-02-06T06:22:00.000-08:00

NEW ORLEANS -- A top medical journal's criticism of a study cited in Vioxx lawsuits is expected to play a part in the retrial of the first federal Vioxx lawsuit _ but it's not clear if it will be a legal hand grenade or a nuclear warhead. The disclosure that some negative data was omitted from the study could make manufacturer Merck & Co. look as if it's hiding something, legal experts say. That is what attorneys for Evelyn Irvin Plunkett, whose husband died after taking the drug for a month, say they can prove in the trial starting Monday.

The first federal trial _ held in Houston in the wake of Hurricane Katrina _ ended with a deadlock. Two jurors said the split was 8-1 in favor of Merck's contention that taking Vioxx had nothing to do with the death of Richard "Dickie" Irvin. The day those deliberations began, the New England Journal of Medicine published criticism _ one step short of retracting the study _ accusing its authors of withholding and deleting relevant data. The information alone is "damaging although not shattering," but its implications could be devastating, Northwestern University law professor Ronald Allen said. Vioxx was a $2.5 billion-a-year seller when Merck pulled it from the market in September 2004 because a study found that taking it for 18 months doubled the risk of heart attacks. An earlier study known as VIGOR, published by the journal in 2000, is being cited in allegations that Merck held back information about the risk of heart attacks. The journal's critique noted that its editors learned that the authors had deleted information about three additional heart attacks not reported in the original study, but reported to the Food and Drug Administration. That would have changed a section about side effects, showing that Vioxx patients had five times as many attacks as those on the pain reliever naproxen, rather than four times as many _ and that patients not considered high-risk were having heart attacks, it said. "Taken together, these inaccuracies and deletions call into question the integrity of the data," the journal said. The editors found a blank table labeled "CV events" _ heart attacks and other cardiovascular side effects _ on a first draft of the VIGOR study found on a computer diskette after the recall. It was deleted from later versions on the same disk. Dr. Gregory Curfman, the journal's executive editor, confirmed through a spokeswoman that software indicated that data was deleted from the table two days before the manuscript was submitted, and identified the deleting editor as "Merck." The company said that all that was taken from the table was data that was put into the body of the article, and it never included information about the three later heart attacks. But, he wrote, the Journal's editors didn't realize the significance of the deletion until Nov. 21, when Curfman was questioned by Plunkett's attorneys. They produced a memo showing that at least two authors knew about the heart attacks at least two weeks before submitting the first of two revisions and 4{ months before publication. Until then, the editors wrote, they had believed the authors didn't know about those heart attacks in time for publication. Merck says the heart attacks occurred after a reporting deadline. The article didn't mention any such deadline, and the journal would have expected updates anyway, Curfman wrote the lead author in an e-mail released by the court. Merck's attorneys, led by Phil Beck, plan to show that VIGOR was "done the right way," meeting all scientific standards, Beck said before the judge imposed a gag order on both sides. The main focus of Merck's arguments, as in the first trial, is that Vioxx had nothing to do with Irvin's death. He already had clogged arteries and a blood clot, they have said in court and in interviews. Plunkett's attorneys, led by Jere Beasley, claim Vioxx caused the clot by affecting an enzyme that thins the blood. Allen said the editorial's precise impact will depend on just how significant the data is considered _ and that, in turn, will help decide what use judges allow. It might simply be folded into the evidence, he said. But it might also be used as a possible indication that Merck was hiding something.
"If juries get a whiff of that, it's going to be devastating," he said. Howard Erichson, a Seton Hall Law School professor, called the editorial a stunning development. But, though he called it "terribly damaging" in a December interview, he now says it won't dramatically alter the case.

"It was about a few data points, not a fundamental rethinking of causation," Erichson said. "It's one piece of evidence that's going to undermine one of the Merck witnesses. "It's there, it's interesting, but it doesn't fundamentally change the course of the litigation." The case being retried starting Monday was the third among more than 9,600 state and federal lawsuits against Merck. Two state jury trials ended with a split decision: a $234 million verdict against Merck in Texas, and one clearing it of blame in New Jersey. Another trial is under way in Texas, and 10 more are scheduled in state and federal courts over the next six months. Merck has set aside $970 million for legal costs, and said it spent $285 million of that last year. The remaining $685 million should last through 2007, it said Tuesday.

Journal Article a Wild Card in Vioxx Trial

2006-02-06T06:20:00.000-08:00

A top medical journal's criticism of a study cited in Vioxx lawsuits is expected to play a part in the retrial of the first federal Vioxx lawsuit - but it's not clear if it will be a legal hand grenade or a nuclear warhead. The disclosure that some negative data was omitted from the study could make manufacturer Merck & Co. look as if it's hiding something, legal experts say. That is what attorneys for Evelyn Irvin Plunkett, whose husband died after taking the drug for a month, say they can prove in the trial starting Monday. The first federal trial - held in Houston in the wake of Hurricane Katrina - ended with a deadlock. Two jurors said the split was 8-1 in favor of Merck's contention that taking Vioxx had nothing to do with the death of Richard "Dickie" Irvin. The day those deliberations began, the New England Journal of Medicine published criticism - one step short of retracting the study - accusing its authors of withholding and deleting relevant data. The information alone is "damaging although not shattering," but its implications could be devastating, Northwestern University law professor Ronald Allen said. Vioxx was a $2.5 billion-a-year seller when Merck pulled it from the market in September 2004 because a study found that taking it for 18 months doubled the risk of heart attacks. An earlier study known as VIGOR, published by the journal in 2000, is being cited in allegations that Merck held back information about the risk of heart attacks. The journal's critique noted that its editors learned that the authors had deleted information about three additional heart attacks not reported in the original study, but reported to the Food and Drug Administration. That would have changed a section about side effects, showing that Vioxx patients had five times as many attacks as those on the pain reliever naproxen, rather than four times as many - and that patients not considered high-risk were having heart attacks, it said. "Taken together, these inaccuracies and deletions call into question the integrity of the data," the journal said. The editors found a blank table labeled "CV events" - heart attacks and other cardiovascular side effects - on a first draft of the VIGOR study found on a computer diskette after the recall. It was deleted from later versions on the same disk. Dr. Gregory Curfman, the journal's executive editor, confirmed through a spokeswoman that software indicated that data was deleted from the table two days before the manuscript was submitted, and identified the deleting editor as "Merck." But, he wrote, the Journal's editors didn't realize the significance of the deletion until Nov. 21, when Curfman was questioned by Plunkett's attorneys. They produced a memo showing that at least two authors knew about the heart attacks at least two weeks before submitting the first of two revisions and 4 1/2 months before publication. Until then, the editors wrote, they had believed the authors didn't know about those heart attacks in time for publication. Merck says the heart attacks occurred after a reporting deadline. The article didn't mention any such deadline, and the journal would have expected updates anyway, Curfman wrote the lead author in an e-mail released by the court. Merck's attorneys, led by Phil Beck, plan to show that VIGOR was "done the right way," meeting all scientific standards, Beck said before the judge imposed a gag order on both sides. The main focus of Merck's arguments, as in the first trial, is that Vioxx had nothing to do with Irvin's death. He already had clogged arteries and a blood clot, they have said in court and in interviews. Plunkett's attorneys, led by Jere Beasley, claim Vioxx caused the clot by affecting an enzyme that thins the blood. Allen said the editorial's precise impact will depend on just how significant the data is considered - and that, in turn, will help decide what use judges allow. It might simply be folded into the evidence, he said. But it might also be used as a possible indication that Merck was hiding something. "If juries get a whiff of that, it's going to be devastating," he said. Howard Erichson, a Seton Hall Law School professor, called the editorial a stunning development. But, though he called it "terribly damaging" in a December interview, he now says it won't dramatically alter the case. "It was about a few data points, not a fundamental rethinking of causation," Erichson said. "It's one piece of evidence that's going to undermine one of the Merck witnesses. "It's there, it's interesting, but it doesn't fundamentally change the course of the litigation." The case being retried starting Monday was the third among more than 9,600 state and federal lawsuits against Merck. Two state jury trials ended with a split decision: a $234 million verdict against Merck in Texas, and one clearing it of blame in New Jersey. Another trial is under way in Texas, and 10 more are scheduled in state and federal courts over the next six months. Merck has set aside $970 million for legal costs, and said it spent $285 million of that last year. The remaining $685 million should last through 2007, it said Tuesday.

Vioxx seen hurting Merck 2005 earnings

2006-02-03T06:40:00.000-08:00

Press/NEW YORK
By THERESA AGOVINOAP Business Writer
Vioxx seen hurting Merck 2005 earnings

JAN. 30 5:40 P.M. ET Vioxx is expected to drag down Merck & Co.'s 2005 earnings when they are reported Tuesday. But what's really frustrating analysts is their inability to assess the drug's potential liability and the toll that litigation preparations are taking on the company.
Divining the impact of the approximately 9,200 suits filed over the now withdrawn blockbuster Vioxx may become easier in the next six months as a verdict pattern emerges from the 11 trials Merck faces in that period. The company has won one case, lost another and the third ended in a mistrial.
At least one analyst expects Merck will take a charge this year to increase its legal reserves for the first time since 2004, to lift the amount beyond $675 million. A charge for potential liability is also a possibility, said Jason Napodano, an analyst at Zacks Independent Research.
Since Merck will be trying some of the cases simultaneously, some analysts worry the crush of litigation may drain executives' energy and concentration at a time when the company faces numerous challenges. They are telling clients to avoid Merck stock until the Vioxx outlook comes into focus.
Scott Henry, an analyst at Oppenheimer & Co, said many drug companies are trading at low prices so there is no reason to buy Merck when the litigation risk is so cloudy. "Why bother with Merck?" asks Henry. "How many venues can they (Merck) really concentrate on?"
Ted Mayer, lead outside counsel for Merck, said the Vioxx litigation was expensive and time-consuming. However, he noted the company knew it would be facing a crush of trials and is very well-prepared. He said there are several scientists well-versed in the Vioxx situation to give testimony. Meanwhile, there are thousands more back at the labs working on new drugs to sell.
"The bench is deep," Mayer said.
On Tuesday, Merck is slated to report 2005 results that will be hurt by the lack of Vioxx sales. Merck took the pain reliever off the market in Sept. 2004 after a study showed it doubled patients' risk of heart attack and strokes after 18 months of use. But the company still banked nine months of revenue. That was gone in 2005. Some analysts expect sales of cholesterol-lowering drug Zocor also fell last year, and will shrivel later this year because the drug loses patent protection in June.
Prudential analyst Tim Anderson expects 2005 earnings will be essentially flat at $2.36 a share, including expenses for stock options.
Last year was a tumultuous one for Merck. The company replaced its chief executive officer with former Merck manufacturing executive Richard T. Clark. During the fourth quarter, Clark announced the company was eliminating 7,000 jobs, closing or selling 31 manufacturing plants and restructuring the company in an attempt to save $4.5 billion to $5 billion by 2010.
Most analysts believe Merck's vaccine to prevent cervical cancer will be another blockbuster but are divided about other products' prospects.
With all Merck must accomplish to turn itself around, Napodano views the Vioxx litigation as a significant distraction. "If Dick Clark is spending 20 percent of his time on Vioxx, that is 20 percent too much," said Napodano.
The first of the 11 new cases began last week in Texas, and a retrial of the first federal case is slated to begin in New Orleans next week. Two cases are slated to be jointly tried in New Jersey in late February.
At least Merck has one less case to worry about: On Monday, Superior Court of New Jersey Judge Carol Higbee dismissed the case of a man who blamed Vioxx for his gastrointestinal problems. According to her motion, Higbee dismissed the case because the plaintiff testified that he would have continued to take Vioxx if he was warned about Vioxx's potential side effects. Merck believes it is the first case dismissed since the drug was pulled.

Vioxx expected to drag on Merck 2005 and play key role in 2006 performance

2006-02-03T06:38:00.000-08:00

Vioxx is expected to drag down Merck & Co.'s 2005 earnings when they are reported Tuesday. But what's really frustrating analysts is their inability to assess the drug's potential liability and the toll that litigation preparations are taking on the company.
Divining the impact of the approximately 9,200 suits filed over the now withdrawn blockbuster Vioxx may become easier in the next six months as a verdict pattern emerges from the 11 trials Merck faces in that period. The company has won one case, lost another and the third ended in a mistrial.
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At least one analyst expects Merck will take a charge this year to increase its legal reserves for the first time since 2004, to lift the amount beyond $675 million. A charge for potential liability is also a possibility, said Jason Napodano, an analyst at Zacks Independent Research.
Since Merck will be trying some of the cases simultaneously, some analysts worry the crush of litigation may drain executives' energy and concentration at a time when the company faces numerous challenges. They are telling clients to avoid Merck stock until the Vioxx outlook comes into focus.
Scott Henry, an analyst at Oppenheimer & Co, said many drug companies are trading at low prices so there is no reason to buy Merck when the litigation risk is so cloudy. “Why bother with Merck?” asks Henry. “How many venues can they (Merck) really concentrate on?”
Ted Mayer, lead outside counsel for Merck, said the Vioxx litigation was expensive and time-consuming. However, he noted the company knew it would be facing a crush of trials and is very well-prepared. He said there are several scientists well-versed in the Vioxx situation to give testimony. Meanwhile, there are thousands more back at the labs working on new drugs to sell.
“The bench is deep,” Mayer said.
On Tuesday, Merck is slated to report 2005 results that will be hurt by the lack of Vioxx sales. Merck took the pain reliever off the market in Sept. 2004 after a study showed it doubled patients' risk of heart attack and strokes after 18 months of use. But the company still banked nine months of revenue. That was gone in 2005. Some analysts expect sales of cholesterol-lowering drug Zocor also fell last year, and will shrivel later this year because the drug loses patent protection in June.
Prudential analyst Tim Anderson expects 2005 earnings will be essentially flat at $2.36 a share, including expenses for stock options.
Last year was a tumultuous one for Merck. The company replaced its chief executive officer with former Merck manufacturing executive Richard T. Clark. During the fourth quarter, Clark announced the company was eliminating 7,000 jobs, closing or selling 31 manufacturing plants and restructuring the company in an attempt to save $4.5 billion to $5 billion by 2010.
Most analysts believe Merck's vaccine to prevent cervical cancer will be another blockbuster but are divided about other products' prospects.
With all Merck must accomplish to turn itself around, Napodano views the Vioxx litigation as a significant distraction. “If Dick Clark is spending 20 percent of his time on Vioxx, that is 20 percent too much,” said Napodano.
The first of the 11 new cases began last week in Texas, and a retrial of the first federal case is slated to begin in New Orleans next week. Two cases are slated to be jointly tried in New Jersey in late February.
At least Merck has one less case to worry about: On Monday, Superior Court of New Jersey Judge Carol Higbee dismissed the case of a man who blamed Vioxx for his gastrointestinal problems. According to her motion, Higbee dismissed the case because the plaintiff testified that he would have continued to take Vioxx if he was warned about Vioxx's potential side effects. Merck believes it is the first case dismissed since the drug was pulled.

Former Merck CEO agrees to testify at N.J. Vioxx trial

2006-02-03T06:36:00.000-08:00

Former Merck & Co. Chairman and Chief Executive Raymond Gilmartin has agreed to a plaintiff lawyers' request that he testify at a Vioxx trial slated to begin in Atlantic City in late February, both sides said. Plaintiff lawyer Mark Lanier said he requested Gilmartin's presence and intends to call him because "when you have to look a jury in the eye it is harder to fudge."

Gilmartin has given testimony in videotaped depositions, but Lanier said that it is always better to have a live witness than a tape. He called the depositions "canned speeches" and said it is harder for witnesses to give soliloquies or avoid questions in the presence of a judge. Lanier said he intends to ask Gilmartin questions that weren't asked in depositions but wouldn't specify what they were. A Merck official said the company believes Gilmartin will be a strong witness, noting his performance in front of a Senate committee hearing in late 2004, when he answered questions about the withdrawal of the pain reliever in September 2004. The drug was taken off the market after a study showed it doubled patients' risk of heart attacks and strokes when taken for longer than 18 months. Gilmartin retired last year and was head of the company when Vioxx was pulled. "Mr. Gilmartin has a good story to tell about Merck's responsible actions concerning Vioxx and the voluntary withdrawal of the product," said Kent Jarrell, a Merck spokesman. Earlier Tuesday, Merck said the number of lawsuits filed against it in connection with the drug has risen to about 9,650 from about 9,200. Merck also announced it had sent aside an additional $295 million for litigation expenses, bringing the total amount it has earmarked for legal costs to $970 million. However, the company said it spent $285 million on defense costs last year, leaving it with $685 million, which it believes will last through 2007. Lanier won the first Vioxx trial last summer. Since then, Merck has won a case while the third ended in a mistrial. A fourth case started in Texas earlier this month. The upcoming trial in New Jersey is slated to combine two plaintiffs, each a man who suffered a nonfatal heart attack after taking Vioxx for more than 18 months. Lanier represents one of the men.

Vioxx expected to drag on Merck 2005 and play key role in 2006 performance

2006-02-03T06:34:00.000-08:00

Merck Profit Up, Adds to Vioxx Legal Funds

2006-02-03T06:32:00.000-08:00

Merck & Co. said Tuesday its profit edged up 2 percent in the fourth quarter on flat sales as the drug company set aside an additional $295 million for legal defense costs related to its withdrawn painkiller Vioxx Vioxx.
Excluding charges for restructuring and taxes associated with repatriating foreign profits, Merck earned 64 cents a share in the latest quarter. That beat by two cents the consensus estimate of analysts surveyed by Thomson Financial.
Shares of Whitehouse Station, N.J.-based Merck shares rose 10 cents to $34.56 in afternoon trading on the New York Stock Exchange New York Stock Exchange. They are near the upper end of their 52-week range of $25.50 to $35.36.
Sales of Zocor, a cholesterol-lowering treatment, fell 18 percent to $1.1 billion in the quarter. The drug will lose patent protection in June.
Merck withdrew Vioxx from the market in September 2004 after a study showed it increased patients‘ risk of heart attacks and strokes. On Tuesday, Merck announced the number of lawsuits filed against it rose to about 9,650 from about 9,200.
Merck also announced its received a subpoena from Attorneys General of 31 states and the District of Columbia who are investigating whether the company violated state consumer protection laws when marketing Vioxx.
Despite the strong quarter, some analysts can‘t figure out how Merck will obtain such growth with its current pipeline and the upcoming loss of exclusivity on Zocor and eventual generics competition for osteoporosis drug Fosomax.
Merck said it is in discussion with over 40 companies about possible deals. However on the conference call, Merck CEO Richard Clark said the estimates didn‘t include any acquisitions or other types of arrangements. He reiterated earlier comments that the company would be interested in purchasing a biotechnology firm, adding that he would prefer one with existing revenues.

Popular Drugs May Fight Arthritis & Breast Cancer

2006-02-03T06:29:00.000-08:00

There's more evidence that the same controversial prescription pain relievers, suspected of raising heart attack risk, may actually help prevent certain cancers.A new study found that women who took the drugs Celebrex or Vioxx every day for two years were up to 71 percent less likely to develop breast cancer.Other anti-inflammatory pain relievers were also found to lower breast cancer risk but the greatest reduction was seen in Celebrex and Vioxx users.And a new study says conventional tests may miss heart disease is as many as three million women.Instead of developing blockages in the main arteries like men do, women tend to experience plaque buildup in smaller blood vessels which are harder to detect.Experts fear that many of these women who come to the doctor complaining of symptoms may be sent away undiagnosed, not realizing that they're at high risk of having a heart attack within the next few years.And another new study finds that cholesterol-lowering drugs called statins may help treat rheumatoid arthritis.Researchers found that in lab test, those drugs prompted the death of certain joint cells linked to the condition. Experts say more studies need to be done to confirm these findings in people who actually have arthritis to see if it can help ease their symptoms.

Merck's Fundamentals Improving Despite Vioxx Headlines

2006-02-03T06:26:00.000-08:00

Standard & Poor’s Equity Research analyst Herman Saftlas raised the target price for Merck shares to $34 from $30 citing “improving fundamentals” after the drug manufacturer reported fourth-quarter 2005 earnings on Tuesday. Merck (nyse: MRK - news - people ) reported fourth-quarter earnings of 64 cents per share, matching the analyst’s estimate. “Results benefited from strong growth in joint venture income and cost controls,” the analyst said in a report. “Although the loss of patent protection on Zocor is expected to lower 2006 earnings per share, we think new drugs and cost cuts should facilitate strong [earnings] growth over the rest of the decade, before restructuring charges,” said the research analyst. In addition, he noted that Merck’s stock remains “vulnerable to Vioxx headlines.” The analyst reiterated a “hold” opinion on Merck.

Fitch Affirms Merck's Senior Unsecured Debt At 'AA'; Outlook Negative

2006-02-03T06:24:00.000-08:00

Fitch has affirmed the ratings for Merck & Co. (Merck) as follows:
-- Issuer Default Rating (IDR) 'AA';
-- Senior unsecured 'AA'
-- Bank loan 'AA';
-- Commercial paper 'F1+'.
The Rating Outlook remains Negative. The ratings apply to approximately $7.32 billion of long- and short-term debt instruments.
Merck faces a host of business risks, most notably potential revenue and cash flow losses due to U.S. patent expirations of key products in the intermediate-term and litigation exposure arising from Vioxx product liability. The Negative Rating Outlook reflects these risks to cash flow generation in addition to possible penalties or fines from investigations by government and regulatory agencies worldwide.
Merck's intellectual property position will be significantly compromised in the 2006-2008 timeframe beginning with the U.S. base patent expirations of Zocor and Proscar in June 2006. Fitch estimates that the revenues and earnings losses from patent expirations (and the global Vioxx withdrawal in September 2004) will not be offset by key product sales and commercialization of the R&D pipeline until 2008, notwithstanding significant business development activity. However, income is expected to be boosted by equity income from Merck's partnerships, especially from the joint venture with Schering-Plough driven by strong sales of Vytorin and Zetia. Fitch will monitor Merck's ability to stabilize total revenues and cash flows, which Fitch anticipates to occur in 2008.
Approximately 9,650 cases alleging personal injury from the use of Vioxx have been filed against Merck by the end of 2005. Fitch favorably views Merck's intention to individually litigate the claims as opposed to offering a global settlement. As a result of this approach, only three cases have been tried over the past six months, with no damages paid by Merck to-date. However, final Vioxx damages and timing of cash outflows are highly uncertain. Fitch will continue to collect information as the litigation progresses through the legal system to ascertain a range of possible exposure which may be significant.
Merck's superior liquidity and light long-term debt maturity schedule will serve to support the company's credit profile in the midst of the operational challenges in the intermediate-term. At the end of the third quarter of 2005, Merck had greater than $14 billion in cash and short-term investments, a $1.5 billion U.S. credit facility, a $3 billion foreign commercial paper program, and free cash flow generation of $2.71 billion (cash flow from operations of $7.71 billion less dividends of $3.49 billion and capital spending of $1.51 billion) for the latest 12-month period ending Sept. 30, 2005. Although free cash flow generation has weakened considerably since the Vioxx market withdrawal, Fitch believes that free cash flow will approximate or exceed $1 billion annually in the intermediate-term, despite Merck's commitment to maintaining its large dividend.
Liquidity is supported by a large domestic cash balance given Merck's repatriation $15.9 billion of foreign earnings in 2005 under the Jobs Creation Act of 2004. Merck had cash, net of debt, of $6.71 billion at the end of the third quarter of 2005. Merck does not have a significant debt maturity until 2008, at which time a $1.38 billion note payable to AstraZeneca matures. Additionally, Merck has the option in 2008 to require a guaranteed payment of $4.7 billion (approximately $3.3 billion, net of the AstraZeneca loan) from AstraZeneca for certain rights and interests pertaining to their joint venture agreement. Fitch estimates that Merck will have cash, net of debt, exceeding $6 billion in the intermediate-term, barring significant acquisition activity and recognizing a commitment to actively repurchasing common shares.
Merck continues to consummate a higher degree of external licensing deals to bolster the late-stage R&D pipeline, which is weaker compared to its peers. Given Merck's expected large domestic cash balance by the end of 2005, large acquisition opportunities may be considered that may assist in strengthening the R&D program and/or transforming a maturing product portfolio. The acquisition strategy of the new CEO, Richard Clark, departs from the anti-merger philosophy of his predecessor, Ray Gilmartin. Fitch anticipates that a large corporate acquisition target may be sought in the intermediate-term.
Fitch's rating definitions and the terms of use of such ratings are available on the agency's public site, www.fitchratings.com. Published ratings, criteria and methodologies are available from this site, at all times. Fitch's code of conduct, confidentiality, conflicts of interest, affiliate firewall, compliance and other relevant policies and procedures are also available from the 'Code of Conduct' section of this site. The issuer did not participate in the rating process other than through the medium of its public disclosure.

Vioxx's next battlefield: New Orleans

2006-02-03T06:21:00.000-08:00

NEW YORK (CNNMoney.com) - The next big battle over Vioxx takes place in New Orleans, a city mired in its own conflicts with nature, the government and itself.
The retrial of Merck v. Plunkett is scheduled to begin Monday in New Orleans -- less than two months after a trial, presided over by U.S. District Judge Eldon Fallon in Houston, ended in a hung jury on Dec. 13.
The Big Easy is Fallon's judicial headquarters, but his entire court was displaced to Texas for the first federal trial due to the damage inflicted by Hurricane Katrina last summer. Fallon, who has consolidated thousands of Vioxx-related lawsuits under federal litigation, wants to stay in New Orleans for the duration.
But is this possible? Will the court be able to assemble a jury from the flood-ravaged city, which saw hundreds of thousands of its residents scattered across the country following Katrina's destruction?
"I've heard through the grapevine that it is going to be difficult to put a jury pool together, and I don't know if they're going to be able to get one," said James McHugh, head of the mass tort department for The Beasley Firm, which represents about 500 plaintiffs who sued Merck in New Jersey state court and about 50 plaintiffs in federal court.
Evelyn Irvin Plunkett of St. Augustine, Fla., sued Merck for the 2001 death of her husband Richard Irvin, who took Vioxx, an arthritis painkiller, for about one month before his fatal heart attack. Merck pulled Vioxx, worth $2.5 billion in annual sales, off the market in 2004 after a study showed links to heart attacks and strokes in patients who took the drug for at least 18 months. However, Merck has said consistently that Vioxx did not cause anyone's death.
Plunkett's case is one of thousands consolidated in federal court, though thousands of suits have also been filed against Merck in the company's home state of New Jersey as well as other state courts. At last count, the Vioxx-related cases against Merck totaled 9,650.
One loss, two wins
Merck lost its first case in Texas but won the second in New Jersey. The third case was Plunkett's mistrial. A fourth case is ongoing in southern Texas.
In a fifth case in New Jersey on Jan. 30, state Superior Court Judge Carol Higbee shot down the lawsuit from plaintiff Edgar Lee Boyd with a summary judgment. Court documents say Boyd failed to show that he was injured by Vioxx.
Lawyers are trying to gauge what kind of jury pool they'll get in a post-apocalyptic city where the poor neighborhoods located near burst levees were emptied, but more affluent neighborhoods on higher ground remained, more or less, intact.
"I would expect they're going to have real difficulty putting a jury pool together," said Jeff Cooper, managing partner for Simmons Cooper, a firm representing about 800 plaintiffs who have sued Merck in New Jersey state court. "If people are back in New Orleans, they're going to be rebuilding their homes or businesses or both. "
Though many residents have left New Orleans forever, others have decided to come back, and still more potential jurors are moving to the city for the first time. This could harm efforts to assemble a jury pool, or help them, depending on who you talk to.
"I don't think they're going to have a difficult time assembling a jury," said Phil Anthony, chief executive officer of DecisionQuest, a trial consulting firm. "While there are a number of citizens who've been displaced, there are also a number of jurors who have moved back in."
To further complicate projections of a jury pool, New Orleans' beating from nature isn't over. On Thursday morning, the city was lashed with severe rainstorms that tore part of the roof off a concourse at Louis Armstrong International Airport and collapsed a house in a hurricane-damaged lakefront neighborhood. Also, a tornado reportedly touched down in the city.
So when, or if, the court manages to assemble a jury, the jurors might not be in the greatest of moods.
'Angry at a lot of things'
"The citizens of New Orleans have been through enormous displacement and generally speaking they're bursting at the seams with anger," said Anthony of DecisionQuest, who has defended drug companies but is not involved in the Vioxx trials. "They're angry at a lot of things. They're angry at no one in particular and everything in general."
Also, jurors might not want to spend weeks sitting in a trial "at a point in their lives where they're trying to rebuild their lives and careers," said Anthony, who said this creates a "dangerous concoction" for Merck.
Some experts believe that jurors frustrated by the government's incompetence in preparing for and responding to Hurricane Katrina might channel their frustrations against Merck and see the drug maker as an enemy, even though Merck had nothing to do with the storm.
"This is a group of people who really feel that not only the government, but corporate America, has really bailed out on them," said Cooper of Simmons Cooper, referring to troubles that residents have had with insurers.
Merck will also have to contend with an editorial from The New England Journal of Medicine. Right after the non-sequestered jury began deliberations in the first Plunkett trial, the prominent medical journal published an editorial reporting that Merck deleted information regarding Vioxx-related deaths from a study it provided the journal in 2000. Merck denied the claim.
"Merck and the authors did everything in a proper scientific manner," said Merck spokesman Kent Jarrell.
Fallon's court verified Thursday that Dr. Gregory Curfman, an editor from the Journal of Medicine, will testify at the retrial. McHugh of The Beasley Firm said this could bode badly for Merck.
"You have Merck saying we submitted the right data; you have the plaintiff saying they didn't," said McHugh, who compared the lawsuit to a traffic case, with an eyewitness acting as tie-breaker. "And then you have the most prestigious medical journal in the world saying 'No, Merck, you ran the red light.'"
Merck spokesman Jarrell said that Fallon has told both sides that a fair jury will be selected, and selection will begin Monday. The plaintiff's lawyer, Andy Birchfield of Beasley Allen, was not permitted to comment on the case, according to his firm.
To find out how much Merck spent on Vioxx litigation last year, click here

Safety Issues Played a Role in Vioxx's Withdrawal from the US Market

2006-01-30T06:24:00.000-08:00

DUBLIN, Ireland--(BUSINESS WIRE)--Jan. 27, 2006--Research and Markets (http://www.researchandmarkets.com/reports/c31670 ) has announced the addition of The Vioxx Withdrawal: Changes and Opportunities for the Industry to their offering.
The safety issues that precipitated the withdrawal of Vioxx from the U.S. market have had a devastating effect on the market potential of the selective COX-2 inhibitor class and raised doubts about the safety of all nonsteroidal anti-inflammatory drugs (NSAIDs). Furthermore, the Vioxx withdrawal sparked a continuing controversy over the FDAs regulation of drugs in the United States and the pharmaceutical industrys promotion of drugs.
This report contrasts the Vioxx withdrawal with other U.S. drug withdrawals, highlighting the unusual set of circumstances surrounding the event, and examines its ramifications for the industry. We discuss potential changes to drug regulation and promotion in the United States, consider how public opinion shapes the decisions of regulators and legislators, and propose that the pharmaceutical industry become a willing and proactive partner in the reforms triggered by this unique event.
Business Implications
-- The withdrawal of Vioxx from the U.S. market occurred against a backdrop of public relations disasters for the FDA, public criticism of rising drug costs, debate over Medicare reform, and increasing concern about the safety of approved drugs. The withdrawal set in motion a series of events likely to change the face of drug regulation and marketing in the United States.
-- Public opinion of the pharmaceutical industry is at an all-time low. Criticism of the cost and quality of drug marketing has heightened in the wake of the Vioxx withdrawal because heavy promotion to doctors and the public is blamed for the vigorous uptake of this drug. Further, the public in the United States blames the rising cost of pharmaceuticals, in part, on what it considers excessive marketing.
-- Following a long and public drug safety debate in the United States, the FDA must rebuild its reputation. The lengthy time that Vioxx remained on the market while its safety was in question and high mortality estimates have been most damaging. Public confidence in the agency has been shaken, and many commentators charge that the FDA's short approval times undermine safety.
-- The FDA has responded by introducing a series of reforms and initiatives aimed at strengthening drug safety programs and increasing the transparency of its operations. A return to slower drug approval times looks set for the future, together with more stringent postmarketing surveillance and rapid, effective response to safety concerns.
-- Pharmaceutical companies need to embrace the coming changes if they are to be successful in the future. There is no question that the industry will be held more accountable for its activities, and public perception may be the key to its success.
Topics Covered
Overview
The Perfect Storm
The Vioxx Withdrawal in Context: A Brief Chronology
Far-Reaching Effects
Outlook
List of Figures and Tables
Figure 1. Share Price History: Comparison of Merck and Pfizer Stocks with Industry Indexes
Figure 2. Public Survey Results of Consumer Confidence
Figure 3. Mean US pproval Times for NMEs, 1984-2003
Figure 4. FDA Drug Approvals Against Percentage of Drugs Withdrawn, Based on Year Approval
Figure 5. Public Survey Results of Attitudes to Drug Advertising
Table 1 Drugs Withdrawn for Safety Reasons in the United States, 1980-2005, in Order of Time on the Market
Table 2. Ten Best-Selling Therapeutic Classes by U.S. Sales, 2004
Table 3. Top Ten Drugs by DTC Spend, 2000
Companies Mentioned
-- AstraZeneca
-- Aventis
-- GlaxoSmithKline
-- Merck & Co.
-- Pfizer
-- Schering-Plough
-- Wyeth
For more information visit http://www.researchandmarkets.com/reports/c31670

Doctors dropped from Vioxx lawsuit

2006-01-30T06:22:00.000-08:00

RIO GRANDE CITY, Texas (AP) _ Two doctors were dropped Thursday from a lawsuit the family of a Rio Grande City man filed claiming that his fatal 2001 heart attack was caused by Merck & Co.'s painkiller Vioxx. The action came on the second day of the nation's fourth Vioxx trial.
The family of Leonel Garza had sued Merck as well as Dr. Michael Evans and Dr. Juan Posada, both of McAllen. They accused the doctors of medical negligence for giving Garza the painkiller, which plaintiffs attorneys said they should have known was dangerous for a man with heart problems. In opening statements Wednesday, attorneys for the defense, the family and the doctors disagreed over whether Vioxx was in Garza's system when he died. Family attorneys say Dr. Evans gave Garza a seven-day supply in late March 2001 and Dr. Posada gave him a month's supply on April 4, 2001. But attorneys for both the doctors and for Merck say there was no evidence that Posada ever gave Vioxx to Garza. Plaintiffs attorneys agreed Thursday afternoon to remove the doctors from the lawsuit. The plaintiffs wanted to focus on Merck, family attorney Mauro Ruiz told The (McAllen) Monitor. "The doctors were very pleased," Ronald Hole, their attorney, told The Associated Press. "But Dr. Posada, of course, never even gave Vioxx and Dr. Evans just gave him the seven-day trial of Vioxx. That was way out of his system before he passed away." Hole said he believed the doctors were brought into the lawsuit to bring it into state court. There was some discussion Thursday afternoon whether the case should be removed to a federal court, but Merck attorneys decided to allow it to remain in state court, Hole said. Merck, based in Whitehouse Station, N.J., is facing hundreds of lawsuits from people who took the once-popular painkiller. The drug was pulled from the market in September 2004, when a study showed it could double risk of heart attack or stroke if taken for 18 months or longer. However, Merck says no such risk has been shown for shorter periods. In previous trials, Merck lost a case in a Texas court and won in a New Jersey court. A federal case ended in a mistrial.

Judge: Attorneys in Vioxx Trial are not to talk to reporters

2006-01-30T06:18:00.000-08:00

NEW ORLEANS -- The judge overseeing the federal Vioxx trial asked attorneys Friday not to talk to reporters. Attorneys for manufacturer Merck & Co. and for Evelyn Plunkett, whose husband died of a heart attack after taking Vioxx for a month, met with U.S. District Judge Eldon Fallon for two hours Friday afternoon.
Fallon also imposed an informal gag before the first federal trial, which ended with the verdict hung 8-1 in Merck's favor. It will be retried starting Feb. 6 in New Orleans. A state jury in Texas awarded $253 million in damages, though state law will cut that to no more than $26.1 million. A New Jersey state court absolved Merck. During the federal court deliberations, the New England Journal of Medicine published an editorial saying that a study which has been a major focus of both federal and state trials had downplayed the drug's possible dangers. Plunkett's attorneys have said the editorial bolsters their claims that Whitehouse Station, N.J.-based Merck hid the drug's dangers. The company pulled the drug in 2004, after another study found that taking it for at least 18 months doubles the risk of heart attacks.

Vioxx trial turning city of 12,000 into media ground zero

2006-01-30T06:16:00.000-08:00

Business suits, BlackBerries and laptops seem to have taken over this town.
As the nation’s fourth Vioxx lawsuit began this week in Rio Grande City, dozens of lawyers, reporters, analysts and expert witnesses descended on this city of about 12,000.
They came for an up-close view of a high-profile, high-stakes lawsuit in which the family of a local man who died while taking the arthritis drug is suing pharmaceutical giant Merck — for $1 billion in punitive damages.
The lawsuit has attracted national attention for a host of reasons, among them the Rio Grande Valley’s reputation for generous civil awards and predictions that the case could prove pivotal for future Vioxx suits. Merck so far has lost one suit, won one, and one was declared a mistrial.
But locals have mixed feelings about having the spotlight on Rio Grande City, and about the outsiders who are shining that spotlight.
"It’s good for the economy, but it’s a short-term economic impact. Whether it brings notoriety to Rio Grande City, well, we’ll see," said Mauro Villarreal, head of the city’s economic development corporation.
Villarreal worried a big award to the plaintiffs could contribute to perceptions of the area as overly friendly toward plaintiffs. In December, the American Tort Reform Association, a national group that advocates curbing awards in civil suits,named the Valley and the Texas Gulf Coast the country’s top "judicial hellhole" for 2005.
Local businesspeople said they welcomed the extra clientele. Still, they dodged questions about potential downsides to the influx of outsiders, many of whom operate at a faster pace than the middle-age and elderly tourists who usually populate the city’s hotels and restaurants at this time of year.
"They’re not Winter Texans. I can tell they’re here on business," said Elizabeth Garza, a front desk clerk at the city’s Best Western Garden Inn.
Twenty people associated with the lawsuit have booked rooms at the inn, Garza said with a little smile, but to protect their privacy, she would not reveal identities. The inn is much fuller than usual for this time of year, she said.
La Borde House, a turn-of-the-century mansion and hotel that is one of the city’s most popular tourist attractions, also is booked. Plaintiffs’ lawyers and support staffers have rented out the downtown hotel for the week, according to Historical Commission employees who oversee the hotel’s operations.
"For us it’s just business," said administrative assistant Nadia Elizondo. "I don’t see any downsides. People are coming here."
On Tuesday morning, the plaintiffs’ legal team had set up shop in the hotel’s normally empty parlor, pushing antique furniture against the walls to make room for a long folding conference table covered with boxes of files. Security evidently was tight: A woman typing on a laptop referred visitors to the Historical Commission, explaining, "Nobody’s allowed in here." A sign on the hotel door said, "Dear visitors, we are currently at full occupancy and cannot allow viewing of the hotel."
At the Starr County Courthouse, the visitor parking lot, mostly empty on an average day, was full. Cars lined both sides of the street leading to the building.
Lawyers on cell phones paced around the building and a woman working on a laptop sat on the front steps of the courthouse. Television camera operators camped out, waiting for the court to recess.
A few feet away, the courthouse’s groundskeeper, 71-year-old Ramiro Diaz, surveyed the scene.
A former migrant laborer who most days can be seen in his standard jeans, western hat and boots, he seemed unperturbed, merely assuming his usual posture and waving to passing acquaintances.

Plaintiff paradise waits for Vioxx trial

2006-01-27T11:10:00.000-08:00

Leonel Garza was 71 when he died of a heart attack, 23 years after being diagnosed with heart disease and decades after a heart attack and a quadruple bypass.
But his lawyers who are suing Merck & Co. say it was the Vioxx that he took for arm pain for 17 days that killed him. Jury selection is scheduled to begin Tuesday in Rio Grande City, a town of about 12,000 people less than five miles from the Texas-Mexico border.
Even though the New Jersey pharmaceutical giant is facing hundreds of lawsuits from people who took the once-popular painkiller before it was pulled from the market, Garza's case would have little hope of making it to trial anywhere but the Rio Grande Valley, some legal experts say.
"What you're seeing is a case that is strong in the merits for Merck but has got to be balanced on the challenges Merck will face in that jurisdiction," said Peter Bicks, a New York City lawyer who has successfully defended large companies in Texas and has been watching the Vioxx litigation. "This jurisdiction has been viewed as one of the toughest jurisdictions for corporate defendants in the country."
But Leila Watson, a Birmingham, Ala., plaintiff attorney with about 70 Vioxx cases, said Garza was "exactly the kind of patient there should have been a warning for."
"Nobody should have given this patient Vioxx, and I don't fault the doctors," she said.
The Valley is a known prize for "venue shopping" by trial lawyers looking for large verdicts from sympathetic jurors, said Bill Summers, president of the Rio Grande Valley Citizens Against Lawsuit Abuse.
"If the company they're suing has even a remote tie to the Valley they want to come here, because they think they can get a better deal," Summers said.
The Valley became the national poster child for the costs of lawsuit abuse in April 2002, when hundreds of doctors closed their offices to protest insurance premiums that had quadrupled in a few years because of the high number of medical malpractice lawsuits.
Doctors began to leave the region in such numbers that some specialties were unavailable to the more than 1 million people who live there.
"Many courts in other counties would toss this case because of the standard that no reasonable juror could find for the plaintiff in this situation," said Victor Schwartz, counsel to the American Tort Reform Association. "It's been our experience that many of the courts in the Rio Grande Valley are very, very friendly to plaintiffs' counsel and let cases go forward."
The ATRA named the overwhelmingly Mexican-American region at the bottom of Texas Rio Grande Valley the nation's top "judicial hellhole" for 2005, a distinction it gives to places where judges uphold "extraordinary" jury awards and seem to favor plaintiffs over defendants.
Bicks said Merck's biggest challenge likely would be with jury selection, when defense attorneys can ferret out jurors who may have a bias against big business.
He cautioned that Merck's argument that Garza didn't take the drug long enough to suffer any heart damage hasn't been the slam dunk Merck might have hoped for.
"From a tactical standpoint a plaintiff may have decided this case isn't worth a pursuing in another jurisdiction," he added. "But from a legal standpoint these cases so far have survived."
Merck & Co. withdrew Vioxx from the market in September 2004 when a study showed it could double risk of heart attack or stroke if taken for 18 months or longer. However, it says no such risk has been shown for shorter periods.
According to Garza's lawyers, Garza was given Vioxx on April 4, 2001, and suffered a fatal heart attack 17 days later. Merck said he was given a week's supply; the plaintiff's lawyer has said it was a month's worth of the drug.
"I'm not aware of any good scientific data, even if you accepted everything plaintiffs say, to show a risk in the time frame in this case," Merck lawyer Richard Josephson said.
The FDA decided in April 2005 that there doesn't appear to be an elevated risk of heart attacks from taking Vioxx for short periods.
Plaintiff attorney Joe Escobedo, who is seeking unspecified damages for Garza's family, did not return calls for comment on the case.
But in other media reports, he has criticized the defense team for a delay tactic that is not unusual in the Valley, in which local state representatives are hired on to the team so that the case cannot open until the close of the biennial legislative session in Austin.
Last January, state Sen. Juan "Chuy" Hinojosa, D-McAllen, joined the defense for one day. He withdrew from the case the next day, saying he didn't know Merck planned to file a continuance.
Hinojosa has gotten bad press before for joining defense teams in high-profile cases, including the first rollover case against Bridgestone/Firestone Inc. to go to trial, in McAllen, in 2001.
Merck quickly hired Rep. Rene Oliveira, D-Brownsville, and filed a second legislative continuance.
Josephson, heading the defense team, said Oliveira has been playing an active role in the case.

Recovering from a bad case of PR

2006-01-27T11:08:00.000-08:00

Everyone agrees that Celebrex and Vioxx were great brands. They told a compelling story of how astute science brought relief to millions of patients. The competition between these two cox-2 brands simply added a bit of extra tension to the tale.
"From a pharmaceutical marketing perspective it was beautiful," admits Mike Rea, managing director of IdeaPharma, a pharmaceutical marketing firm. "This was a market waiting for a brand. The audience was sold something they didn't need but definitely really wanted. It was more than a side effect that all but killed the drugs."As far as branding is concerned, Vioxx and Celebrex both did a great job," Rea continues. "They both talked up the selectivity and how they avoided the side effects of other NSAIDS. The world believed that cox-2s were safer. And while they were talking about the GI [gastrointestinal] safety, they were not talking about the cardiovascular safety profile."According to Rea, the side effects profiles of the cox-2s were more or less the same as for older non-steroidal anti-inflammatory drugs (NSAIDS) -- only the incidence of severe side effects was lower. Furthermore, much cardiovascular safety data was also in the public domain. "But these were brands, not products," he says. "I reckon physicians would probably have still prescribed these products. I'm not sure the world was looking with open eyes."Merck and Pfizer's actions are something for the courts to decide. However, concerns about the cardiovascular safety of the cox-2s were being raised in medical publications as early as 2001. Rumors grew, concerns were voiced. Then on 30 September 2004, Merck announced that, following the analysis of three-year's worth of data in a post-marketing study, Vioxx would be voluntarily withdrawn worldwide.All hell broke out. Merck shares immediately plunged 30 percent. Other cox-2s fell under the spotlight. In December 2004 a clinical trial showed an increased risk in cardiovascular events for patients taking Pfizer's Celebrex, and the fear of a class effect from cox-2 products spread. The panic even reached non-cox-2 anti-inflammatory painkillers; trials were stopped because of a perceived increase in risk."This is one of the problems with branding," admits Jon Parton, global director of branding at pharmaceutical company AstraZeneca. "The pessimist says you shouldn't do global branding, because if it goes wrong it goes down big-style everywhere. But my belief is that you plan for success. If you have a problem you own up to it."This is a good lesson to learn, but a hard one to implement when it comes to the crunch. David Wood, chairman of Interbrand Wood Healthcare, a healthcare consultancy, says that the companies were understandably cautious in their reaction to the safety concerns. "They were slow at first. They seemed a bit more defensive, with companies assuring that their products didn't have the safety issues that were claimed. Then there appeared to be attempts to justify along the lines of 'We are doing all we can to ensure the safety of patients.' Announcements of withdrawals followed (Vioxx and then Bextra). It almost seemed as if companies were waiting to see what the competition was doing first before taking steps to withdraw."Of course, the decision to withdraw a product with annual sales of over $2 billion and a flagship brand is not made lightly or quickly. "These were enormously important, and profitable, products for each of these companies, each of which had been approved by the regulatory authorities, so quite understandably they were not going to be withdrawn easily nor without adequate evidence," says Wood."There is probably no ideal way to pull a product for safety reasons," Wood continues. "The product brand is probably scarred forever, and the corporate brand is obviously severely impacted as well. Clearly in this case Merck is continuing to suffer far more than Pfizer, since Bextra was only available through hospitals, and consequently was little known by the public at large, while Vioxx was a very high-visibility, 'public' brand."IdeaPharma's Rea believes that the situation could have been handled much better, however, and some of the corporate damage could have been avoided. "Merck acted more like Perrier did when traces of benzene were found in its water," he says. "First it denied everything, then had to keep backtracking. Sure, Merck was unlucky to have the more 'dangerous' drug, but it always seemed to be forced into communication. And the actual withdrawal was particularly badly handled?it was almost an admission of guilt in the first place." Companies should look like they are always in control. "The people who should know most about a drug is the manufacturer," Rea says. "[B]eing forced into the open by statements and data from others looks bad. Instead you need to be in front of the curve of knowledge. Pfizer seemed to be better at stating publicly the facts of research and being on the front foot by offering analyses. Pfizer seemed to know what was going on."AstraZeneca's Parton says that honesty and openness are the only options for long-term success. "If Pfizer or Merck are shown to have misled deliberately then no one will trust the company anymore, and that would affect all other brands. It is good business to be ethical. It is not in our interests to by sly and crooked. Otherwise you end up like Enron. We are not whiter than white, but being honest is best for business."Wood agrees and suggests that product brands should have a strategy for handling such events -- including their own withdrawal. His advice is to "be ready, have a plan, be open and honest, and reinforce the parent brand by being smart and responsible. Step one is to recognize that there is always the potential for issues because we work in a very difficult industry. And the fact is that no amount of clinical trial testing can truly and adequately simulate actual years in the marketplace. Also learn that safety is the number one issue for society and that is what corporate brands need to stand for. Safety and responsibility."This is the kind of situation in which whatever you've been saying about yourself, and having your corporate brand stand for, must be mirrored in your actions," Wood continues. "Merck has long held a reputation of strong ethical responsibility with its consumers and customers, represented by their 'people before profits' mantra.? However, their lack of fast action, and demonstrated commitment to doing the right thing, were doubtless seen to run counter to the kinds of statements they had been making about themselves."Rea also notes that Merck tended to respond to developments as Merck, whereas Celebrex often came out with Celebrex press statements. "By responding badly you affect how you go forward as a company. It is not just Vioxx but Merck that is damaged now. On the other hand Pfizer has lost Bextra and may lose Celebrex, but we probably won't lose Pfizer."Wood, in contrast, suggests that such major issues should be given adequate attention from top management. "The companies could probably have used their corporate brand and top management to much better effect. The standard in handling this kind of event was set by J&J and McNeil years ago during the Tylenol poisoning, when the chairman took personal responsibility, acted fast, and communicated openly and fully with all relevant constituencies. Unfortunately top management of both companies was largely silent on this occasion," he continues, referring to Merck and Pfizer.The advice all sounds obvious, really: good behavior gets results. But does it really make much difference? Rea admits that, as with a lot of branding, it is difficult to measure, but he does think that the contrasting situations of Pfizer and Merck today may stem from their handling of the cox-2 catastrophe. Appropriate and "on brand" behavior, even in a crisis, may be enough to make the difference between failure or survival. In this case, it may have influenced the FDA's decisions when it reviewed all the cox-2 data in February 2005. "The panel was very split. It is difficult to say that the final decision was due to a difference in the molecules or marketing, but it could be a bit of both," says Rea. "Not everyone agreed that the risk profile of Celebrex was okay to leave it on the market. But maybe Pfizer just looked a bit more credible and a few votes were swayed in its favor."Nevertheless, whether Merck or Pfizer comes out of this affair intact, it has had a devastating effect on the credibility of the pharmaceutical industry as a whole. No matter how well a pharma company manages its brand, chances are its reputation will still rank lower than most tobacco companies. "It's not just the responsibility of individual companies -- the industry as a whole must make a more concerted effort to not simply counter negative publicity, but to tell its story to a public that frankly knows very little about the realities of the [...] industry," states Wood. "We need to be careful about demonizing an industry, which, ultimately, is about improving and saving human lives. But the industry must start helping itself, and these recent events have served only to set it back."

In the Pharmaceutical Industry the Pain Drug Market is Expected to Be Worth $25 Billion over the Next Few Years.

2006-01-27T11:07:00.000-08:00

Research and Markets (http://www.researchandmarkets.com/reports/c31301) has announced the addition of Pain Drugs: Problems and Opportunities to their offering.
Pain is one of the largest pharmaceutical markets, forecast to reach $25 billion in the next few years, but it has also been plagued by problems including the failure of Vioxx and Celebrex. This report examines the nature of pain, what went wrong with the COX-2 inhibitors, and the alternative approaches and drugs that may fill the resulting void.
Pain comes in many forms and treatments range from non-drug therapies like psychological, surgical and neurostimulus, to analgesics, opiods and even cannabinoids. This report explores these various methods and identifies drugs currently on the market or under development that may replace the COX-2 inhibitors.
Reasons to Purchase
-- Understand the nature of pain and why it is a therapeutic challenge
-- Identify the companies and the drugs and treatment protocols that are poised to replace the void left by the failure of COX-2 inhibitors
-- Analyze the competitive landscape of the $25 billion pain market
Target Audience
-- Business development execs/managers seeking partnership opportunities
-- Marketing and senior execs/managers wishing to understand the competitive landscape
-- Research and development execs/managers wanting to know the current state-of-the-art
-- Venture capitalists and fund managers seeking investments
-- Analysts and journalists researching the market for treating pain
-- Others seeking to understand the driving factors and market dynamics
Drugs Mentioned
-- Carbex
-- Celebrex
-- Codeine
-- Imitrex
-- Luvox
-- Marplan
-- Nardil
-- Neurontin
-- OxyContin
-- Parnate
-- Paxil
-- Prozac
-- Topamax
-- Tylenol/Acetaminophen
-- Vicodin
-- Vioxx
-- - Xyrem
-- Zarontin
-- Zoloft
-- Zomig
Topics Covered
Introduction
The Nature of Pain
Pain's Many Forms
-- Acute Pain
-- Internal Organs
-- Migraine Headache
-- Cluster Headache
-- Chronic Pain
-- Neuropathic Pain and Cancer Pain
-- Phantom Limb Pain and Other Manifestations
Treatment - Non-drug
-- Psychological
-- Local and Regional Methods
-- Surgery
-- Sympathetic Blockade
-- Neurostimulatory Methods
-- Anesthesia Pumps
Treatment - Drugs
-- Non-opioid (non-narcotic) Analgesics
-- Opioids (narcotics)
-- Tranquilizers
Non-painkiller Drugs
-- Anti-epileptics
-- Antidepressants
-- Cannabinoids
Companies Mentioned
Abbott
Pfizer
Purdue
Merck
Medtronic
Janssen-Cilag
Johnson & Johnson
Takeda
For more information visit http://www.researchandmarkets.com/reports/c31301

Vioxx: Showdown in Rio Grande

2006-01-27T11:06:00.000-08:00

NEW YORK (CNNMoney.com) - The Garza family faces off against Merck this week in a Texas border town, in the fourth lawsuit to blame Vioxx, the market-pulled painkiller, for causing heart attacks.
The family of Leonel Garza, 71, sued Merck and blames Vioxx for Garza's fatal heart attack in 2001. Jury selection begins on Tuesday, at a state court in Rio Grande City, a town of 12,000 in Starr County near the border with Mexico. Judge Alex Galbert will preside over the case, held in 229th judicial district court.
Nearly 10,000 lawsuits have been filed against Merck, following the withdrawal of Vioxx from the market on Sept. 30, 2004. Merck (down $0.19 to $33.06, Research), based in Whitehouse Station, N.J., pulled Vioxx, an arthritis painkiller, off the market after a study showed an increased risk of heart attacks and strokes in patients using the drug for at least 18 months.
Garza was given a one-week supply of Vioxx 25 mg samples for pain in his arm about one month before his death on April 21, 2001, according to Merck. Merck also said that Garza had a 23-year history of heart disease and had survived one heart attack prior to taking Vioxx.
Ted Mayer of Hughes, Hubbard & Reed, outside counsel for Merck, said in a recent press release that "there is no reliable scientific evidence that Vioxx caused Mr. Garza's heart attack. At the time of Mr. Garza's heart attack, he exhibited numerous major risk factors for coronary artery disease."
Repeated calls for comment by CNNMoney were not returned by Hockema, Tippit & Escobedo, the Texas firm representing the Garza family.
This will be the third trial to be held in Texas, and its outcome could be seen as a tie-breaker in the ongoing series of suits against Merck.
The most recent trial, the Plunkett v. Merck wrongful death case, ended in a hung jury on Dec. 13, 2005 in a federal court in Houston under U.S. District Court Judge Eldon Fallon, has been scheduled for retrial on Feb. 6. The retrial is scheduled to begin on Feb. 6 in New Orleans, the original seat of Fallon's court before it was displaced by the destruction of Hurricane Katrina.
Evelyn Irvin Plunkett of St. Augustine, Fla., sued Merck for the 2001 death of her husband Richard Irvin, who took the drug for one month before his fatal heart attack. The jury was unable to reach a verdict. Right after the non-sequestered jury began deliberations, the New England Journal of Medicine published an editorial reporting that Merck had deleted information regarding Vioxx-related deaths from a study it provided to the journal in 2000. Merck denied the claim, but plaintiff lawyer Jere Beasley said it undermines the credibility of Merck's key witness Alise Reicin, the company's vice president of clinical research.
Merck lost its first Vioxx case in Texas state court, but won the second case in its home state of New Jersey.

Vioxx suit contends death a 'reaction'

2006-01-27T11:05:00.000-08:00

RIO GRANDE CITY - Attorneys for the family of 71-year-old man argued Wednesday that his fatal 2001 heart attack was a sudden reaction to Merck & Co.'s painkiller Vioxx and not the result of 23 years of heart disease.
Joe Escobedo, the Leonel Garza family attorney, said in his opening statement that Garza was told after a stress test shortly before he died that he had a less than 2 percent chance of dying of a heart attack within a year.
"Vioxx caused Mr. Garza's death," Escobedo said. "Mr. Garza did have [cardiovascular] risk factors, but they were under control."
The suit was filed against the drug's maker by relatives of Garza, of Rio Grande City. He suffered a fatal heart attack in 2001, and the jury may ultimately decide if that was the result of 23 years of heart disease or the Vioxx he took for arm pain the 17 days before he died.
Garza's attorneys are seeking $1 billion in punitive damages from Merck.

Federal court releases medical journal e-mails over Vioxx study

2006-01-27T11:03:00.000-08:00

NEW ORLEANS -- In the world of scientific research, the language was strong stuff. "Your explanation lacked scientific objectivity," an editor for the New England Journal of Medicine wrote to a researcher whose study, published in 2000, has become a major focus of federal and state lawsuits involving the painkiller Vioxx.

"That's pretty serious. That's pretty serious," Dr. Mark Frankel, director of the Scientific Freedom, Responsibility and Law program at the American Association for the Advancement of Science, said Wednesday. Researchers are expected to be utterly impartial. "This is serious criticism. Obviously, this case has implications far beyond the journal," Frankel said. He said he is looking forward to reading the researchers' response. Dr. Claire Bombardier, the lead researcher from the University of Toronto, has sent a response to the journal, and the university will comment once it is published, university spokesman Steven de Sousa said Wednesday. A brief statement from the journal said communications with authors are confidential. "Once our concerns have been fully pursued and answered, we will publish the results," it said. The e-mail from its executive editor, Dr. Gregory D. Curfman, was released Tuesday by U.S. District Judge Eldon Fallon, who is in charge of pretrial matters for all 4,050 federal lawsuits against manufacturer Merck & Co. Another 5,150 cases have been filed in state courts, many of them in New Jersey. So far, the jury message has been mixed. A Texas state court awarded $253 million in damages, though state law will cut that to at most $26.1 million. A New Jersey state court absolved Merck. The first federal trial ended with a jury hung 8-1 in Merck's favor, and will be retried starting Feb. 6 in New Orleans. In all three trials, each side has cited Bombardier's study, called VIGOR, as proving its point about whether Merck promptly disclosed the drug's cardiac risks. But while the federal jury was deliberating whether Merck was responsible for Richard Irvin's death in Florida, the New England Journal of Medicine published an editorial criticizing researchers for leaving out critical data from the VIGOR report. Lawyers for Irvin's widow have said the editorial bolsters their claims that Merck hid the drug's dangers. The company pulled the drug in 2004, after another study found that taking it for at least 18 months doubles the risk of heart attacks. Kent Jarrell, a spokesman for Merck's attorneys, repeated earlier statements: nothing was hidden; the heart attacks occurred after a study cut-off date; and the Food and Drug Administration had all of the data before the study was published. Attorneys for the company questioned Curfman on Tuesday. "We are prepared when that issue comes up in any trial to explain what happened and how we believe that everything was done properly by Merck," Jarrell said Wednesday. In his e-mail to the VIGOR study's lead author, Curfman listed five points which the journal expects the authors to make in a correction. One was omission of three heart attacks from the data; another that including them "would have invalidated your claim" that only people already at risk of a heart attack were at a greater risk from Vioxx. The article doesn't mention a cut-off date for reporting heart attacks, Curfman wrote, and even if it had, NEJM and other journals expect updates. "This is especially important for a potentially serious drug adverse effect" such as a heart attack, he wrote. Curfman's comment about lack of objectivity came in a written discussion of the study's statement that people taking naproxen had one-quarter as many heart attacks as those on Vioxx because naproxen protects the heart. It should have noted the flip side _ the possibility that Vioxx might be harmful, Curfman wrote. "The relative risks were presented so as to favor naproxen and discount the possibility that rofecoxib might be harmful."

Journal editors to be deposed ahead of next Vioxx trials

2006-01-20T06:26:00.000-08:00

TRENTON, N.J. - A current editor and former editor of the New England Journal of Medicine, which last month criticized drug maker Merck & Co. for withholding data from a published study on its withdrawn painkiller Vioxx, will be grilled next week by the company's lawyers.
The depositions, ahead of the next round of product liability trials over Merck's former blockbuster arthritis pill, will be held next Tuesday and Wednesday, Paul Shaw, an attorney representing the editors, said Wednesday.
The depositions are to center on a December editorial in the journal, one of the world's most respected medical publications, that said Merck concealed three heart attacks suffered by patients in a large study published in the journal in November 2000. Whitehouse Station, N.J.-based Merck has said those heart attacks happened after the study's cut-off date for side effects, but journal editors say such data is routinely added until a study's publication.
The editorial also alleges the study's authors deleted some relevant data before submitting their article.
"There was no material deleted from the submission to the journal," but some was moved from a graph into the body of the text, said Kent Jarrell, a spokesman for Merck's outside counsel.
The 2000 study, known by the acronym VIGOR, has been a key part of Vioxx product liability trials so far, with both sides using it in their arguments over whether Merck promptly disclosed the drug's cardiac risks. Merck pulled the drug from the market in September 2004 after research showed Vioxx doubled the risk of heart attacks and strokes after 18 months' use.
Merck has won one state case, in New Jersey, and lost one, in Texas. The first federal case ended in a hung jury last month.
After the journal's editorial was widely reported, attorneys for Merck subpoenaed multiple NEJM editors and sought information on its "peer reviewers," independent scientists who critique studies before publication. The editors subpoenaed include editor in chief Dr. Jeffrey M. Drazen and executive editor Dr. Gregory D. Curfman.
"The court should prohibit Merck from engaging in these retaliatory tactics because they run afoul of the protection journalists enjoy under the First Amendment," Shaw wrote in a motion seeking to block the subpoenas.
On Tuesday, U.S. District Judge Eldon Fallon of New Orleans, who is overseeing thousands of consolidated federal lawsuits over Vioxx, ruled that Merck can depose Curfman but not Drazen.
Curfman said Wednesday that he had been subpoenaed and will comply.
In addition, Merck can depose a second person, a former New England Journal editor involved in handling of the VIGOR study, Shaw said. That person has not been publicly identified, and Shaw would not do so.
Fallon rejected Merck's bid to get information on the identities of the journal's peer reviewers.
"He's protecting the integrity of the peer review process," said lawyer Chris Seeger, co-lead counsel for the consolidated federal suits. He said the subpoenas continue Merck's "history of intimidating scientists who question anything on the safety of Vioxx."
Seeger said information from the two editors' depositions can be used by both plaintiff and defense lawyers in all future Vioxx cases. Merck faced at least 9,200 lawsuits around the country, including about 4,000 in New Jersey, as of Nov. 30.
"We're very happy with Judge Fallon's ruling," Seeger said, adding he believes the depositions will hurt Merck more than any plaintiffs.
Among the next cases slated for trial is the retrial of the federal case. It is scheduled to begin Feb. 6 in New Orleans.
Merck shares fell 18 cents to close at $33.03 Wednesday on the New York Stock Exchange.

'Vioxx like' drugs may still be best option for arthritis write scientists

2006-01-20T06:25:00.000-08:00

Scientists believe that despite the current concerns around anti-inflammatory drugs like Vioxx, they may still be the best option for treating some forms of arthritis.
In a Nature Reviews of Drug Discovery article this month the researchers from Imperial College London and Queen Mary, University of London examine the use of selective inhibitors of cyclo-oxygenase-2 (COX-2).
They argue that although this class of drugs, which includes Vioxx, has been associated with an increase in the risk of cardiovascular events such as heart attacks and strokes in some patients, the same may be true for traditional non-steroid anti-inflammatory drugs (NSAIDs).
All NSAIDs, including COX-2 inhibitors, work by blocking the actions of both COX-1 and COX-2 enzymes. Blocking COX-2 relieves inflammation and pain, but blocking COX-1 can increase the risk of gastric ulcers and bleeds. For this reason COX-2 selective drugs were developed with the simple aim that they would retain the therapeutic actions of NSAIDs (linked to inhibition of COX-2) but lose the gastric side effects (linked to inhibition of COX-1).
The researchers reviewed over one hundred papers on the subject and looked at the latest recommendations from organisations such as the American Federal Drugs Administration on the use of COX-2 inhibitors and NSAIDs.
The researchers point out that the calls for the removal of COX-2 inhibitors, and a return to using NSAIDs, may cause additional problems. Although NSAIDs have been marketed for a number of years, they have never been required to meet the clinical trial standards now set for COX-2 inhibitors, meaning they may not be any safer.
Professor Jane Mitchell , from Imperial College London, and one of the reviews authors, said: "Although some COX-2 drugs have been reported to increase the risk of heart attack and stroke, they may still remain the best option for treating arthritis in some patients without cardiovascular risk factors who cannot tolerate traditional NSAIDs because of gastric side effects."
Professor Mitchell added: "This review shows us that despite the large scale use of NSAIDs and COX-2 inhibitors for a number of years, we still need more information on their benefits and potential risks and that more research needs to be done in this area. Looking at existing evidence, however, it would seem COX-2 inhibitors may be the best option for some patients. They are as effective as traditional NSAIDs, but with less gastric side effects than some older drugs."

Pfizer quarter beats forecasts

2006-01-20T06:24:00.000-08:00

LONDON (SHARECAST) - Pfizer was in demand today after the drug giant said cost cutting helped it top Wall Street’s expectations for the fourth quarter, although generic competition sent profits lower. The New York based group reported earnings of $2.73bn, or 37 cents per share, versus $2.83bn, or 38 cents, a year ago. Revenue was down 9% to $13.6bn, but beat forecasts of £13.27bn. Ignoring one-time items, group earnings were 51 cents, trumping forecasts of around 42 cents per share. Cholesterol drug Lipitor remained the world's top-selling prescription drug with sales up 3% to $3.36bn during the period, with annual sales up 12% to $12.19bn. Cheaper generic drugs ate away at sales of the group’s drugs that have lost patent protection, sending total sales for 2005 2% lower to $51.3bn. Epilepsy treatment Neurontin saw sales slump 71%, hypertension drug Accupril sank 74%, while sales of arthritis treatment Celebrex tumbled 53% following the recall of Merck’s similar drug Vioxx in 2004. Pfizer is due to release new financial forecasts for 2006 in February.

Vioxx faces 2 federal suits

2006-01-16T06:17:00.000-08:00

NEW ORLEANS — The next two federal lawsuits claiming that the painkiller Vioxx caused heart attacks or other cardiovascular problems are scheduled for trial this spring.The case that ended last month in a mistrial and will be retried in February looks at whether very short-term use could cause a heart attack.Merck & Co. withdrew Vioxx from the market in September of last year when a study showed it could double the risk of heart attack or stroke if taken for 18 months or longer.The case of New Orleans resident Ellis Diaz, considered a medium-term user of the drug, is scheduled March 13, Kent Jarrell, spokesman for Merck's attorneys, said late Friday.The case involving long-term use is that of Charles Borowicz, Jarrell said. He said attorneys agreed that Borowicz' case will be refiled as a federal case and heard in April in New Orleans.

Drugs in '05: Much Promise, Little Payoff

2006-01-13T09:27:00.000-08:00

Even as pharmaceutical companies poured a record amount of money into drug development in 2005, the industry's research drought grew worse.

According to newly released statistics from the Food and Drug Administration, it approved only 20 new drugs, down from 36 in 2004. Only once in last 10 years has the number of newly approved drugs been lower than last year's figure.
The dry spell in 2005 came even as spending on research by the industry reached a new high, passing $38 billion. And in a rarity, several major companies failed to win approval for a new drug invented in their own labs, including Pfizer, Eli Lilly and Johnson & Johnson.
The decline in drug development came as scientists in and outside the companies were making great strides in genomics and other sorts of basic research into the way diseases develop, opening many potential new targets for treatment. Yet such progress in the laboratory has not translated so far into many new drugs on the market.
Some analysts say that the drug industry is in a cyclical trough, and that the number of new drugs - not just new applications for drugs already on the market - will start rising within a few years as research investments begin to pay off. But the F.D.A. and the companies seem to agree that the process for testing and developing new drugs needs improvement.
"Our concern is that the development process itself is not keeping up at a fast enough pace to match the progress on the discovery end," said Dr. Scott Gottlieb, the agency's deputy commissioner for medical and scientific affairs.
The F.D.A. is looking for ways to speed the approval of new treatments - like approving drugs based on "surrogate endpoints," whether, for example, a cancer drug causes tumors to shrink instead of whether it prolongs the life of patients. It was on such a basis that the F.D.A. last month approved Nexavar, a Bayer drug for treating kidney cancer.
But like finding new treatments, diagnosing the problem of drug development is easier than figuring out a solution. Even as the F.D.A. looks for ways to speed the testing of new treatments, members of Congress and some consumer groups are calling for even more testing before drugs are approved.
The low output from research last year was even worse than the top-line figures might indicate. In 2004, important cancer treatments including Avastin, by Genentech, and Tarceva, through a partnership of Genentech and OSI Pharmaceuticals, were among the therapies that regulators allowed onto the market. The drugs that were approved were mostly for rare diseases like chronic iron overload, a condition for which the Novartis medicine Exjade received clearance.
In the meantime, the agency delayed approval of prominent new treatments like Pargluva, a diabetes drug from Bristol-Myers Squibb and Merck, and Exubera, a form of inhaled insulin from Pfizer.
The paucity of new products is a big reason that the stock prices of large drug makers have tended to fare poorly in recent years. Shares of Pfizer, the industry leader, for example, reached a peak of $49 in July 2000 and have trended downward since, closing yesterday at $24.44.
The drought in new drugs has led some industry executives to complain that the F.D.A. is denying approval to good new treatments because of the criticism the agency has faced from lawmakers over Vioxx. Merck stopped selling its arthritis painkiller Vioxx in 2004 after a clinical trial showed that it increased the risks of heart attacks and strokes in patients taking it for 18 months or longer. Some other studies found heart attack risks as early as 2000, and the F.D.A. has been criticized for not forcing Merck to withdraw the drug earlier or to warn doctors prominently of such risks.
Dr. Gottlieb said that the agency's attitude toward approving new drugs had changed only marginally, if at all. Its approval rate has been roughly flat for the last several years, but companies are submitting fewer applications, he said.
Albert Rauch, a drug industry analyst at A. G. Edwards & Sons, says that the F.D.A. should not be blamed for the drop in new approvals last year.
"Some of the drugs that didn't make it through, they had issues," Mr. Rauch said. "If you come up with something that's unique and really has a unique advantage, the F.D.A.'s very receptive to that."
Mr. Rauch said he believed that the industry was probably at the bottom of the development cycle and that the number of new drugs would increase in the next few years, as some sophisticated research techniques started to bear fruit. "When you're talking about targets, there's a lot of them out there," Mr. Rauch said. "But those targets didn't become evident until after 1995. It's only been 10 years, and it typically takes at least 10 years to get a product to market."
Researching and developing a drug is a long and arduous process. Genentech's work leading to Avastin, for example, began in 1989 - 15 years before the drug's approval. Scientists first identify the cellular process of disease within the body. They may search for proteins that cancerous tumors release in order to spread, or receptors on the surface of a cell that become the targets of viruses.
The drug company then searches for chemical compounds or proteins that are able to interact with the targets the scientists have found - without damaging cells in other parts of the body. If a treatment appears to have therapeutic effects in test-tube and animal trials, the companies then move on to Phase I human testing, when a handful of healthy volunteers are given the therapy to make sure that it is safe enough for wider testing. In Phase II testing, the drug is tried on a few dozen to a few hundred patients for safety and effectiveness.
Finally, in Phase III development, the drug is tested in large-scale trials with as many as several thousand patients to demonstrate its effectiveness and to search for rarer side effects.
If the treatment is shown to be unsafe or ineffective at any stage, it fails development and is put aside.
According to a report in December from Merrill Lynch, the number of potential new drugs in Phase I and II testing has nearly doubled in the last decade, to 1,971 in 2004 from 1,010 in 1995. But that has not translated into success in Phase III development; the number of drugs in Phase III has been flat at fewer than 400.
"R&D statistics over the past decade have been disappointing," Merrill's analysts wrote in their report. Still, the analysts predicted that companies would continue to increase research spending and expand their pipelines of early-stage drugs.
The advances in early-stage development, though, may be increasing the rate of attrition as drugs move into later stages, according to the report. "Technological advances may have allowed companies to more easily create new therapies, thus boosting the number of compounds in early development," it said. "But the increasing complexity of the targeted disease could mean that it is hard to predict efficacy and safety."
Analysts note that the biotechnology industry is still coming into its own and that the medical payoffs from genomics still lie mainly in the future.
So far, said Robert Rech, a managing director at Ferghana Partners, a specialty investment bank that specializes in the drug industry, the increased knowledge about disease processes has created as many questions as answers. "We have all this extra information, and all it's done is complicated everything," he said. "It's almost like we know too much, because for everything that we learn, it almost brings up two new questions."
Still, the companies that Ferghana works with are optimistic that the drought in drug development will not last forever, Mr. Rech said. "If you're in the industry, you certainly don't sense any lack of activity. I think we will get there, but we're only 15 years into this. It just takes time."

Second Texas Vioxx trial slated for January

2006-01-13T09:25:00.000-08:00

NEW YORK (Reuters) - Merck & Co. (MRK.N: Quote, Profile, Research), which lost its first Vioxx product liability case last summer in Texas, on Tuesday said a trial involving another Texas Vioxx user who suffered a fatal heart attack will begin January 24.
Merck said it believes evidence in the case will show that its withdrawn painkiller Vioxx did not cause the heart attack of 71-year-old Leonel Garza Sr., who died of the attack on April 21, 2001.
"Approximately one month before his death, Mr. Garza was given a one-week supply of Vioxx 25 milligram samples for arm pain," Merck said in a release.
Merck, which contends Vioxx has not posed a heart danger to short-term users of Vioxx, said Garza had a 23-year history of cardiovascular disease and had suffered a prior heart attack.
Merck pulled Vioxx off the market in September 2004 after a study showed the drug, which had annual sales of $2.5 billion, significantly increased the risk of heart attacks and strokes in patients who had been taking it for at least 18 months.
Thousands of U.S. state and federal lawsuits have since been filed against Merck by former Vioxx users or their survivors, alleging harm from the widely advertised pill.
In the earlier Texas case, a state jury on August 19 found Merck negligent in the death of a 59-year-old marathoner and awarded his widow $253 million. The amount is expected to be greatly reduced under Texas law that limits awards.
Since losing that first state trial in Texas, a New Jersey state jury found Merck did not commit consumer fraud or conceal risks associated with the painkiller in the case of a short-term Vioxx user who blamed the drug for his heart attack.
The first federal Vioxx trial, held in Houston last year, ended with a hung jury. The suit is scheduled to be retried beginning on February 6 in New Orleans.
Merck shares were off 31 cents at $33.35 on Tuesday morning trade on the NYSE, in line with moderate declines for the drug sector.

VIOXX(R) Trial Update: Statement on VIOXX(R) Product Liability Trial Scheduled in Starr County, Texas

2006-01-13T09:24:00.000-08:00

Merck & Co., Inc. will conduct a vigorous defense in theproduct liability lawsuit, Garza v. Heart Clinic, Evans, Posada andMerck & Co., Inc., which is scheduled to go to trial before a jury onJan. 24, 2006, in the 229th Judicial District Court of Starr County,Texas. The company believes the evidence in this case will show thatVIOXX did not cause the unfortunate heart attack of Leonel Garza, Sr.
Mr. Garza, 71, died of a heart attack on April 21, 2001, following23 years of cardiovascular disease and a prior heart attack.Approximately one month before his death, Mr. Garza was given aone-week supply of VIOXX 25 mg samples for arm pain.
"There is no reliable scientific evidence that VIOXX caused Mr.Garza's heart attack," said Ted Mayer of Hughes Hubbard & Reed,outside counsel for Merck. "At the time of Mr. Garza's heart attack,he exhibited numerous major risk factors for coronary artery disease.His autopsy report lists acute myocardial infarction as the cause ofhis death and notes evidence of severe atherosclerotic disease in allof Mr. Garza's coronary arteries. We are confident that any fair jurywill find that VIOXX had nothing to do with the unfortunate passing ofMr. Garza since there is no reliable scientific evidence thatshort-term use of VIOXX increases cardiovascular risk."
Texas State District Court Judge Alex W. Gabert will preside overthe case.
A separate VIOXX product liability case, Plunkett v. Merck, isscheduled to be retried before a jury in New Orleans before FederalDistrict Court Judge Eldon Fallon on Feb. 6, 2006. Jurors in theoriginal trial, held in Houston in December, were unable to reach averdict, resulting in a mistrial.
"We intend to defend these cases individually over many years,"said Kenneth C. Frazier, senior vice president and general counsel ofMerck. "Merck acted responsibly - from researching VIOXX prior toapproval in clinical trials involving almost 10,000 patients - tomonitoring the medicine while it was on the market - to voluntarilywithdrawing the medicine when it did."
The company voluntarily withdrew VIOXX in September 2004 inresponse to a Merck-sponsored study, called APPROVe. In that study,there was an increased relative risk of thrombotic events in patientstaking VIOXX continuously for 18 months compared to patients taking asugar pill. That increased relative risk did not appear to bestatistically significant until 30 months or more of continuous use,and there was no detectable difference in risk for patients takingVIOXX for a short duration.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceuticalcompany dedicated to putting patients first. Established in 1891,Merck currently discovers, develops, manufactures and markets vaccinesand medicines to address unmet medical needs. The Company devotesextensive efforts to increase access to medicines through far-reachingprograms that not only donate Merck medicines but help deliver them tothe people who need them. Merck also publishes unbiased healthinformation as a not-for-profit service. For more information, visitwww.merck.com.
Forward-Looking Statement
This press release contains "forward-looking statements" as thatterm is defined in the Private Securities Litigation Reform Act of1995. These statements are based on management's current expectationsand involve risks and uncertainties, which may cause results to differmaterially from those set forth in the statements. The forward-lookingstatements may include statements regarding product development,product potential or financial performance. No forward-lookingstatement can be guaranteed, and actual results may differ materiallyfrom those projected. Merck undertakes no obligation to publiclyupdate any forward-looking statement, whether as a result of newinformation, future events, or otherwise. Forward-looking statementsin this press release should be evaluated together with the manyuncertainties that affect Merck's business, particularly thosementioned in the cautionary statements in Item 1 of Merck's Form 10-Kfor the year ended Dec. 31, 2004, and in its periodic reports on Form10-Q and Form 8-K, which the Company incorporates by reference.

Fourth Vioxx Trial Set for The Valley

2006-01-13T09:23:00.000-08:00

A jury in the Rio Grande Valley in Texas, a traditionally plaintiff-friendly location, will hear the nation's next Vioxx suit. The trial in Felicia Garza, et al. v. Michael D. Evans, M.D., et al. is set to begin on Jan. 24 in 229th District Judge Alex W. Gabert's court in Starr County. The trial will be the first in 2006 and the fourth Vioxx suit to go to a jury, following a plaintiff's state-court win in Angleton -- the verdict totaled $253.5 million -- a defense win in state court in New Jersey, and a mistrial in federal court in Houston. The family of Leonel Garza Sr. alleges in its second amended petition that the Vioxx a physician gave Garza on April 4, 2001, caused his fatal heart attack on April 21, 2001. The plaintiffs are suing Vioxx manufacturer Merck & Co. Inc., of New Jersey, and two of Garza's doctors, Michael D. Evans and Juan D. Posada. The plaintiffs allege in their petition that Evans, Posada and Merck were negligent, and they also bring claims of strict liability, breach of warranties, negligent misrepresentation, gross neglect and gross negligence against Merck. In the petition, the plaintiffs, who include Garza's widow, three sons and daughter, seek unspecified actual and punitive damages. Garza died at age 71. According to the second amended petition, Evans and Posada are represented by Ronald G. Hole, a partner in McAllen's Hole & Alvarez, but Hole could not immediately be reached for comment. In a written statement on Jan. 10, Merck defense lawyer Ted Mayer, a partner in Hughes, Hubbard & Reed in New York, says there is "no reliable evidence" the pain-killer Vioxx caused Garza's heart attack. "We are confident that any fair jury will find that Vioxx had nothing to do with the unfortunate passing of Mr. Garza," Mayer says. The plaintiffs' lawyers filed the suit in March 2003. On two occasions, once in 2003 and once in 2005, Merck removed the suit to federal court, but in November 2005, U.S. District Judge Eldon Fallon of New Orleans, who is presiding over the federal multidistrict Vioxx litigation, remanded Garza to the 229th District in Starr County. Last week, Gabert set the trial for Jan. 24. The plaintiffs team in Garza includes Joe Escobedo Jr., David H. Hockema, John L. Tippit and Mauro F. Ruiz, all of Hockema, Tippit & Escobedo in Edinburg; Alberto A. Munoz II of the Law Office of Alberto A. Munoz II in Edinburg; and Kathryn Snapka, a partner in Corpus Christi's Snapka & Turman. Kent Jarrell, a Vioxx trial spokesman for Merck, says the defense trial team may include, depending on lawyer schedules, Richard Josephson and Travis Sales, partners in Baker Botts in Houston; Ricardo Cedillo, a shareholder in Davis, Cedillo & Mendoza in San Antonio; Rene Oliveria, a partner in Roerig, Oliveria & Fisher in Brownsville; and/or Jaime Saenz, a partner in Rodriguez, Colvin, Chaney & Saenz of Brownsville. Merck voluntarily withdrew Vioxx from the market in September 2004 after a study indicated the drug could double the risk of heart attack or stroke if taken for 18 months or longer.

Second Texas Vioxx Trial to Start Jan. 24

2006-01-13T09:21:00.000-08:00

Merck & Co. (MRK), which lost its first Vioxx product liability case last summer in Texas, Tuesday said a trial involving another Texas Vioxx user who suffered a fatal heart attack will begin Jan. 24.
Merck said it believes evidence in the case will show that its withdrawn painkiller Vioxx did not cause the heart attack of 71-year-old Leonel Garza Sr., who died of the attack on April 21, 2001.
"Approximately one month before his death, Mr. Garza was given a one-week supply of Vioxx 25 milligram samples for arm pain," Merck said in a release.
Merck, which contends Vioxx has not posed a heart danger to short-term users of Vioxx, said Garza had a 23-year history of cardiovascular disease and had suffered a prior heart attack.
Merck pulled Vioxx off the market in September 2004 after a study showed the drug, which had annual sales of $2.5 billion, significantly increased the risk of heart attacks and strokes in patients who had been taking it for at least 18 months.
Thousands of U.S. state and federal lawsuits have since been filed against Merck by former Vioxx users or their survivors, alleging harm from the widely advertised pill.
In the earlier Texas case, a state jury on Aug. 19 found Merck negligent in the death of a 59-year-old marathoner and awarded his widow $253 million. The amount is expected to be greatly reduced under Texas law that limits awards.
Since losing that first state trial in Texas, a New Jersey state jury found Merck did not commit consumer fraud or conceal risks associated with the painkiller in the case of a short-term Vioxx user who blamed the drug for his heart attack.
The first federal Vioxx trial, held in Houston last year, ended with a hung jury. The suit is scheduled to be retried beginning on Feb. 6 in New Orleans.
Merck shares were off 31 cents at $33.35 on Tuesday morning on the NYSE, in line with moderate declines for the drug sector.

Pharma's year of trouble and strife

2006-01-13T09:18:00.000-08:00

For many reasons, 2005 was a year that the pharmaceutical industry would rather forget. Public confidence in the industry is arguably at an all-time low, and safety and policy issues overshadowed scientific achievements.
Safety in the spotlight
The year began, much as 2004 had ended, with Vioxx (rofecoxib; Merck) and the other cyclooxygenase-2 (COX2) inhibitors dominating the headlines. In February, an FDA Advisory Committee narrowly voted 17–15 in favour of the overall risk–benefit profile for Vioxx supporting marketing in the US. The committee voted 17–13 with two abstentions that Bextra (valdecoxib; Pfizer) should continue to be marketed, and voted a more unanimous 31–1 in favour of continued marketing of Celebrex (celecoxib; Pfizer). Bextra was withdrawn in April, after another risk was highlighted — a severe skin reaction called Stevens–Johnson syndrome — and an injectable form of the drug (Dynastat) was rejected by the FDA in September.
In the first of the lawsuit trials against Vioxx, a jury in Angleton, Texas, ordered Merck to pay a staggering US$253.4 million to Carol Ernst, whose husband died after taking the drug. The jury's decision seemed to be based more on how much Merck knew about the risks before it withdrew the drug than on whether the drug was responsible for Robert Ernst's death from an arrhythmia (heart attack being the only cardiovascular adverse event associated with Vioxx). Merck won the second case on its home turf in New Jersey, but the first of the federal cases was declared a mistrial (see page 10).
Merck is already feeling the effects of the Vioxx saga. CEO Raymond Gilmartin departed from his post in May, and was replaced by Richard Clark, the former head of the manufacturing division. With further pressure from the patent on Merck's best-selling drug, the statin Zocor (simvastatin), expiring in 2006 (see 'Six to watch in 2006') the company announced major cuts, with 7,000 jobs set to go.
The year ended with Pfizer saying it will spend up to $100 million for a trial run by Steven Nissen at the Cleveland Clinic which will compare Celebrex head-to-head with naproxen and ibuprofen in arthritis patients who are at a high risk of cardiovascular disease.
More safety woes

The first of the cases on cardiovascular-related deaths linked with Vioxx entered the courts.
The COX2 inhibitors were not the only drugs hounded by safety problems. Elan and Biogen Idec's antibody treatment for multiple sclerosis Tysabri (natalizumab) was withdrawn in February after two patients developed the rare demyelinating disease progressive multifocal leukoencephalopathy (PML), with one case being fatal. It seemed that Tysabri's mode of action — inhibiting 4 integrin — could suppress the immune system so much it allowed the activation of the normally latent JC virus, which is associated with PML. A third case identified soon after increased fears of more cases and that this could be a class effect. But a safety evaluation of more than 1,000 patients failed to uncover any more cases, and Tysabri has been resubmitted for FDA approval. A decision is expected by mid-2006.
Safety doubts also surrounded Johnson & Johnson's heart failure drug Natrecor (nesiritide). An analysis of pooled trial data showed that the drug might increase mortality or cause renal damage (Sackner–Bernstein, J. et al. JAMA 293, 1900–1905; 2005). J & J convened a panel headed by Harvard University's Eugene Braunwald, which concluded that Natrecor's use should be restricted to the most ill patients and that a large clinical trial should be conducted to prove that the drug is safe.
Natrecor was one of the five approved drugs that FDA whistleblower David Graham named in a Congress hearing in 2004 as posing a similar threat to the public's health as Vioxx. In November, the FDA requested that another of the named drugs, GlaxoSmithKline's asthma treatment Serevent (salmeterol xinafoate), should carry warnings that it might increase the risk and severity of asthma episodes (see page 11). Warnings were placed on other drugs containing long-acting -agonists — GSK's Advair (fluticasone propionate; salmeterol xinafoate) and Schering-Plough's Foradil (formoterol fumarate) — and the agency also recommended restricting their use to patients who failed to respond to other asthma treatments.
Race discrimination
The highly controversial subject of 'race-based medicine' came to the fore in June when the FDA approved NitroMed's BiDil for heart failure in African-American patients only. BiDil is a combination of two generic drugs — isosorbide dinitrate and hydralazine — that increase nitric oxide levels which relaxes the smooth muscle cells that line arteries.
It's generally agreed that race is a crude surrogate maker for disease, and many feared that approving BiDil would set a worrying ethical precedent. But given that middle-aged African-Americans are more than twice as likely to die from heart failure as Caucasians of similar age, there is a major clinical need for an effective treatment. And studies showed that BiDil, at least in part, met that need. Self-described black patients taking BiDil had a 43% reduction in death and a 39% decrease in hospitalization for heart failure compared with placebo (Taylor, A. L. et al. NEJM 351, 2049–2057; 2005).
Although much more needs to be understood about the ethnic variation in drug response, BiDil's approval highlighted the need to identify markers to explain and predict such clinical observations to develop better drugs. Another study from deCODE Genetics showed that a particular variant of a gene that boosts inflammation called LTA4H raises the risk of heart attack in African-Americans by more than 250% (Helgadottir, A. et al. Nature Genet. Published online: 10 Nov 2005; ). The company is currently developing a drug candidate, called DG031, which inhibits the inflammation pathway that LTA4H functions through, and is creating a diagnostic test for the gene.
Flu fears grow

Public health concerns: BiDil, the first race-based drug to be approved, and fears of an avian flu pandemic dominated the headlines in 2005.
The growing fear of an avian flu pandemic was arguably the biggest health story of the year. As isolated cases of infection with the deadly H5N1 avian flu virus strain slowly spread across the globe from South East Asia, it became clear what little we can do to protect against a pandemic.
With current vaccine technologies unable to deal with a potential pandemic (despite, for example, the US government's pledge to increase funding for vaccine development, including a long-overdue boost for research on cell-culture-based methods), Roche and Gilead's antiviral drug Tamiflu (oseltamivir) emerged as the best available treatment against the H5N1 strain. Demand for Tamiflu bordered on the hysterical: governments and states fought to stockpile the yellow and white capsules, and doses of Tamiflu even found themselves put up for sale on the online auction site eBay.
For a drug that hadn't been selling well, Tamiflu's instant fame was good news for its manufacturers, but it also brought several problems. With the current supply thought to cover just 2% of the world population, production of the drug needed to be ramped up way above Roche's current capabilities to make enough doses for a potential pandemic. Generics companies succeeded in forcing Roche to allow other manufacturers to produce the antiviral drug as well. Companies such as Cipla claimed that they could make Tamiflu within months, despite Roche's claims that it would take a newcomer 2–3 years to start from scratch and produce significant amounts of the drug through the complex ten-step synthetic process.
But a bigger problem seemed to be that the starting material, shikimic acid, comes from a limited source — the Chinese cooking spice star anise. Ironically, one solution to the problem of manufacturing the antiviral could lie within bacteria. One-third of Roche's Tamiflu supplies is currently made by engineering bacteria to produce shikimic acid; whether this technology can be scaled up to cope with the increased demand remains to be seen.
Stem-cell pioneer under fire
Stem-cell therapies took a huge step towards fulfilling their long-hyped potential, yet within months took a bigger step backwards.
The leading group in the field, a South Korean team headed by Woo Suk Hwang, stunned the research community by showing that they could make embryonic stem-cell lines tailored to individual patients much more efficiently than was thought possible (Hwang, W. S. et al. Science 308, 1777–1783; 2005). Months later, it was announced that a World Stem Cell Foundation would be launched, where Hwang's group would use their know-how to create custom stem-cell lines for scientists worldwide.
But just a few weeks after the announcement came the bombshell that the South Korean team obtained human egg cells unethically from two junior researchers in an early study, and Hwang resigned from the new foundation. The dust has yet to settle on this saga, but at the time of going to press Hwang was also facing allegations over the validity of the scientific data presented in the Science paper (see page 10). See Boxes 1,3 and 4.

Stocks Rise Despite Smaller Intel Forecast

2006-01-13T09:14:00.000-08:00

Stocks rose in early trading Friday as Wall Street reconciled itself with Intel Corp.'s tightened forecast and a recent runup in energy prices. Friday's advance followed two sessions of moderate losses as investors scoured for any news that might bring revive its yearend rally after a two-week hiatus. Many are hoping for a solid holiday shopping season, with lower gasoline prices contributing to improving consumer confidence.
Oil and gas prices were higher in premarket activity but fell slightly despite a snowstorm in the Northeast that was expected to drive a spike in heating fuel demand. On the New York Mercantile Exchange, natural gas lost 13.4 cents to $14.86 per 1,000 cubic feet, and a barrel of light crude dropped 6 cents to $60.60. In the first hour of trading, the Dow Jones industrial average gained 9.13, or 0.08 percent, to 10,764.25. Broader stock indicators were also higher. The Standard & Poor's 500 index was up 2.07, or 0.16 percent, at 1,257.91, and the Nasdaq composite index added 4.20, or 0.19 percent, to 2,250.66. Bond prices fell, with the yield on the 10-year Treasury note climbing to 4.5 percent from 4.46 percent late Thursday. The dollar was mixed against other major currencies in European trading, while gold prices lingered near record highs. Intel trimmed $200 million from both the high and low ends of its fourth-quarter sales estimate, narrowing its forecast to a range of $10.4 billion to $10.6 billion. Intel's revision, which fell slightly below Wall Street expectations, follows a sharpened outlook at rival Texas Instruments and improved guidance from Xilinx Inc. Intel fell 23 cents to $25.47, while TI gained 25 cents to $32.88 and Xilinx rose 51 cents to $26.53. Merck & Co. slipped 71 cents to $28.97 after the New England Journal of Medicine on Thursday said researchers failed to disclose that three patients suffered heart attacks in a 2000 Merck-funded study of its Vioxx painkiller. Meanwhile, jurors in the first federal Vioxx trial were to continue deliberating whether Merck failed to warn about the drug's risks. Rural telecommunications provider Alltel Corp. said it plans to become a pure wireless carrier by spinning off its fixed-line phone business and merging that unit with Valor Communications Group Inc. in a $4.9 billion deal. Alltel was up $2.07 at $66.89, and Valor added 29 cents to $12.53. The Russell 2000 index of smaller companies rose 0.99, or 0.14 percent, to 686.21. Overseas, Japan's Nikkei stock average jumped 1.45 percent. In afternoon trading, Britain's FTSE 100 fell 0.27 percent, Germany's DAX index sank 0.12 percent, and France's CAC-40 was lower by 0.3 percent.

Merck witness has chink in armor

2006-01-09T06:21:00.000-08:00

During the past five months, Merck researcher Alise Reicin has stood toe-to-toe with some of the nation's best trial lawyers.
Described by her bosses at the New Jersey pharmaceutical company as a "tenacious defender of the Vioxx franchise," she has been Merck's most reliable witness in the three trials so far involving the once-popular painkiller.
Now, she's on trial as much as the drug itself.
That's because of a bombshell last month from the editors of the New England Journal of Medicine. They accused the authors of a key study on Vioxx of fudging the data, and making the drug look safer than it was. Reicin was a co-author of the Vioxx study, and plaintiffs attorneys say the editorial undercuts her testimony that Merck acted responsibly.
"The essence of the problem is when you have a witness who has a halo over her head, and crystalline credibility, any ding in that can shatter the entire aura and cast her as a profits-before-science marketing adjunct," said Sam Davis, a Teaneck attorney who is representing hundreds of Vioxx plaintiffs.
Reicin, a 45-year-old scientist, who lives in Englewood, helped design the clinical trials that led to the drug's regulatory approval in 1999. And she has consistently provided the scientific underpinning to Merck's claim it acted in good faith before pulling the drug from the market in September 2004, after a study linked it to an elevated risk of heart attack and stroke.
More importantly, she has shown the ability to win over a jury. After the first New Jersey case in Atlantic City last fall, jurors said they found her to be particularly credible. Merck won that case, after losing weeks earlier in a case in Texas. Later, a federal lawsuit in Houston ended in a mistrial. Merck faces more than 9,000 lawsuits around the country.
"Clearly, Dr. Reicin is a star witness for Merck," said plaintiff attorney Andy Birchfield, who nonetheless said he is looking forward to raising the New England Journal's concerns in his retrial of the first federal Vioxx case, which begins Feb. 6 in New Orleans.
LOOKING FOR INCONSISTENCIES After the editorial appeared, plaintiff attorneys immediately began combing Reicin's testimony for discrepancies. Four weeks later, no blatant contradictions have emerged.
Texas attorney Mark Lanier, who won a multimillion-dollar verdict against Merck last summer in the first Vioxx trial, has backed away from comments that he planned to pass information along to law enforcement officials. In an e-mail last week, he said he is saving inconsistencies he has found for a Vioxx case he is trying in New Jersey at the end of February.
Chris Seeger, one of the plaintiff attorneys who lost the first Vioxx case in New Jersey last fall, has said he wanted to add the New England Journal revelations to his motion for a new trial.
Seeger had not done so as of Friday, but it is possible the information could be included in time for a hearing before Superior Court Judge Carol Higbee later this month. Seeger did not return calls seeking comment.
Merck, meanwhile, insists it is keeping Reicin in its lineup of witnesses. Company lawyers pored over her testimony in the three trials, and found nothing of concern, said Ted Mayer, an outside counsel for Merck.
"What she testified to was entirely truthful and straightforward," Mayer said.
GOOD WITH THE JURY It's not surprising Merck will continue to rely on Reicin, even if the risks have gotten higher. In court, she is imperturbable under questioning. During breaks in testimony in Atlantic City in October, she routinely turned to the jury and smiled -- at one point, mouthing the words "It's cold in here," according to Davis, who was attending the trial.
"She comes across to the jury as knowledgeable, authoritative and articulate," said Daniel Keller, a New York plaintiff attorney who sat in on her testimony in the first Vioxx trial in Texas last summer. "She did a pretty good job presenting alternate views of some of Merck's most damning documents."
The medical journal's editors claim the authors of a Vioxx study named Vigor, published in 2000, failed to mention three heart attacks among those given the painkiller and also deleted other relevant safety information. The heart attacks were significant, the editors say, because they occurred in patients at a low risk of cardiovascular problems.
The authors of the study have said the three heart attacks occurred after a firm cut-off point for data, and are preparing a formal response to the New England Journal.
Reicin, who declined to be interviewed while litigation continues, did offer a brief written statement on the controversy.
"Ensuring the integrity of scientific data is of utmost concern to me as a doctor and scientist, and I would never do anything to compromise that principle," she said. "I have been honest and consistent in my testimony regarding the availability of the Vigor data and its disclosure to the New England Journal of Medicine and the Food & Drug Administration."
Keller, a former defense lawyer for pharmaceutical companies who now represents Vioxx plaintiffs, said Reicin will have to spend part of her testimony defending herself, instead of Merck.
"Its pretty simple: it dilutes her testimony," he said. "She'll be prepared to deal with it, but the facts are the facts."
'INTENSE AND SERIOUS' Reicin, who took Vioxx herself before it was withdrawn, is married to a managing director of Morgan Stanley, and has three children ranging in age from 9 to 15. Her father helped run a unit of a family business, M. Putterman & Co., that makes gym floor covers, industrial containment systems and other products. In testimony in Atlantic City, Reicin said her parents stressed the importance of education, and giving back to society.
"I developed an interest in science, an aptitude for science, and so it was kind of natural to decide to pursue a career in medicine, where I could combine science with the ability to help people," she said during the Atlantic City trial in October.
Reicin graduated summa cum laude from Barnard and went on to Harvard Medical School. She did her residency at Columbia-Presbyterian Medical Center, and conducted research on the HIV virus at Columbia.
"AIDs was the epidemic of my generation," she said.
Her mentor at the university, Stephen Goff, called her a terrific researcher who did well at "very hard-core, basic science."
"She's incredibly intense," Goff said. "She's very serious about science."
Reicin moved to Merck because she believed she could have a greater impact on patients' lives.
Despite her responsibilities on litigation, Mayer said Reicin continues to work on clinical research. He declined to say what projects they are.
"That continues to be her primary role," she said.

Larry Sobal column: There's a mess beyond Vioxx

2006-01-09T06:20:00.000-08:00

Last month, it was all over the news that a U.S. federal judge in Houston ruled that the latest trial involving Vioxx was a mistrial due to a hung jury.
To refresh your memory, Vioxx is a prescription painkiller manufactured by drug giant Merck. The drug was released in the market in 1999 after the Food and Drug Administration ruled it safe. After being dogged by safety concerns, Merck pulled the drug from the market in September 2004 after studies showed in doubled the risk of heart attacks and strokes in patients who took it for 18 months or longer.
The Houston trial is just one of 7,000 Vioxx lawsuits against Merck. So far, one jury has awarded $253 million to the family of an individual who died while taking Vioxx while another jury found no Merck wrongdoing in a similar case.
While this makes for good media fodder, the question I have — so should you — is whether the Vioxx situation is really a symptom of a diseased pharmaceutical industry in need of major reform.
There are huge dollars at stake in the world of drug development. Vioxx was a blockbuster drug that generated roughly $2.5 billion in annual sales and Americans are now spending in excess of $200 billion a year on prescription drugs. Drugs are the fastest-rising component of health care costs.
At first glance, it would appear that drug manufacturers are simply pursuing capitalistic incentives geared to turn out a steady stream of innovative medicines that lengthen life, enhance its quality and avert more expensive care. If successful, we reap the benefits of miracle drugs and they reap the benefits of handsome profits. However, once you get past this altruistic view, a closer inspection reveals major concerns.
My first concern is that the profitability of drug companies is the barometer by which all other industries are measured. In fact, for more than two decades, the drug industry has clearly been the most profitable in the U.S. In 2002 the combined profits for the 10 drug companies in the Fortune 500 ($35.9 billion) were greater than the cumulative profits for all other 490 companies put together ($33.7 billion).
My next concern is that drug industry is not a model of free enterprise, but one utterly dependent on government-granted monopolies (in the form of patents from the FDA) and is no longer focused on brining new miracle drugs to market. The reality is there are few new innovative drugs being brought to market. The vast majority of "new" drugs entering the market are variations on existing drugs. These "me-too" drugs are often just a molecular variation of an existing product and developed just before the patent expires.
There is a lot at stake related to patent approval. Once patent exclusivity expires, usually averaging around 14 years, generics flood the market and are often priced at less than 20 percent of the name brand and profits subsequently plummet.
Since the FDA controls the drug approval process, one would hope that this organization takes an unbiased stance and always acts in the best interests of the public. With around 3,000 lobbyists targeting Washington, no other industry spends more money with more people in order to sway public policy, and the FDA has made some questionable decisions to protest pharmaceuticals.
Among the changes I advocate are that the FDA should only provide patent protection to a drug if it is deemed to be "better" in some distinguishable way versus other drugs already on the market. In addition, the FDA needs to take back control of how drugs are tested by the manufacturers so that all clinical trials are fully disclosed. These are but a few of the changes needed to clean up the corporate drug scene.

Drug profits infect medical studies

2006-01-09T06:19:00.000-08:00

SEVERAL OF OUR most venerated scientific journals have recently been besmirched by allegations of scientific misconduct. Shocking? We should be just as shocked as Inspector Renault when he discovered gambling at Rick's Cafe in Casablanca.First, the New England Journal of Medicine made public its concerns about crucial data having been withheld from its 2000 report on a study sponsored by Merck exaggerating the safety of its blockbuster drug Vioxx, now withdrawn. Then the lead author of a seminal article published in the journal Science reporting the creation of viable stem cells from cloned human embryos admitted he falsified results and resigned his academic post in disgrace.
This week brings the news that a Johnson & Johnson subsidiary failed to include the deaths of two patients in a clinical trial of its new drug for heart failure, Natrecor, in an article published in the Journal of Emergency Medicine.Why shouldn't we be surprised? Because over the last 25 years, clinical research has been largely privatized. Three-quarters of the clinical studies published in the three most respected medical journals (the New England Journal of Medicine, the Journal of the American Medical Assn. and the Lancet) are now commercially funded. As a result, our medical knowledge grows not in the direction that best improves our health but toward corporate profits, the way that plants grow toward sunlight.This wasn't always so. Before 1980, most medical studies were publicly funded, and most academic researchers scorned industry support. Now, however, the vast majority of clinical trials are commercially funded, and with the financial stakes so high, there is mounting evidence of individual scientists and corporations manipulating their findings.Even our most trusted journals are dependent on drug-company money. Drug makers don't just buy advertising in their pages. According to Richard Horton, editor of the Lancet, they also pay up to $1.75 million for reprints of articles favorable to their drugs, which sales reps then hand out to doctors.And many journal articles are biased in favor of their sponsors' products. A 2003 report in the Journal of the American Medical Assn. found that clinical studies funded by drug companies are three times more likely to conclude that the sponsor's drug is the treatment of choice, compared to studies of the same drug that were not commercially funded. (This study of the effects of commercial bias, by the way, was funded by Danish research institutions.) The disturbing conclusion is that most of the evidence in what doctors believe to be "evidence-based medicine" is more infomercial than dispassionate science.It's vital to protect the integrity of our medical knowledge. But the current peer review system alone can't do the job. The journals, and the peer reviewers they rely on, are in the untenable position of having to trust that corporate sponsors have accurately and completely reported their findings. At present, journal editors and peer reviewers typically are not allowed unrestricted access to the data from commercially sponsored research. Amazingly, many drug company-funded researchers who write the articles are also not allowed access to all of the data the company has collected.There is no better cautionary tale than the unwarranted success of Vioxx. Greater safety was the only reason for doctors to have prescribed Vioxx, given that it provided no better relief of arthritis symptoms or pain and cost up to 10 times more than the older anti-inflammatory drug, naproxen (sold without a prescription as Aleve). But Merck's own study clearly showed that Vioxx was more dangerous than naproxen overall and caused significantly more heart attacks, blood clots and strokes — whether or not the patient had a previous history of cardiovascular disease.SO WHY DID American doctors prescribe $7 billion worth of Vioxx after Merck and the Food and Drug Administration knew all this?Because the New England Journal article that ostensibly reported the results of Merck's study didn't even mention either the cardiovascular or the overall dangers of Vioxx. Instead, it reported only selective data on heart attacks and strokes, allowing Merck to claim that Vioxx wasn't a risk to people without a history of these problems.The Journal's editors are now accusing Merck of withholding critical data. Shame on Merck. But shame on the Journal too for not insisting that the article include a discussion of the most important complications. Doctors were left with the impression that Vioxx was safer than naproxen when exactly the opposite was true.The Journal again misled its readers in 2001, when one of its influential review articles dismissed the dangers of Vioxx as perhaps reflecting "the play of chance." This article was published seven months after FDA reviewers' concerns and Merck's own research data, which documented the dangers, had been posted on the FDA's website. Worse, the Journal violated its own policy prohibiting scientists with conflicts of interest from writing review articles. (Both authors had financial ties to Merck.) That the Journal disclosed those ties mitigates neither its ethical breach nor the consequences of its repeated understatement of the risks of Vioxx.This is hardly an academic argument. According to an article in the Lancet, based on Merck's own data Vioxx probably caused between 88,000 and 144,000 cases of serious heart disease.The stem cell and Natrecor debacles offer further evidence that the problem is not just individual bad actors or occasional lapses of scientific integrity by drug makers. It's that even the most prestigious journals are unable to perform the quality control that doctors take for granted.Sadly, the evidence shows that it's time for the journals to change their policies from trust to "trust, but verify." They should introduce a new standard requiring an independent audit of the accuracy and completeness of research reports before they are sent out for peer review. These scientific auditors should be statisticians and medical experts who are completely free of conflicts of interest and are given unfettered access to the data.The journals will rightfully claim they cannot afford to pay for such scientific oversight. But the lack of oversight is even more costly. Americans waste billions each year on drugs of dubious value. Until we find a way to fund quality controls on published research, the cost of our medical care will continue to soar and our health will suffer.

Vioxx case set in Starr County

2006-01-09T06:18:00.000-08:00

The nation’s fourth lawsuit against Merck & Co.’s Vioxx painkiller, linked to heart problems, is set for jury selection Jan. 24 in a Starr County courtroom.
The family of Leonel Garza sued the New Jersey pharmaceutical company, two McAllen doctors and a Harlingen clinic in March 2003 after the 71-year-old Rio Grande City man died of a heart attack one month after taking Vioxx. The 12-member jury that Merck’s and Garza’s lawyers will select from Starr County residents is expected to render a tie-breaking verdict against the nation’s fifth-largest pharmaceutical company, which faces more than 9,000 lawsuits over the painkiller recalled in 2004 after studies showed it increased the risk of heart disease and stroke.
So far, Merck has lost one case, won another and had a third end in a mistrial.
In August, a Brazoria County jury found the company responsible in the drug’s first case and ordered Merck to pay $253 million to the family of a Wal-Mart manager who died of heart problems after taking Vioxx for about eight months. The company is appealing the verdict. In November, an Atlantic City, N.J., jury found the company not responsible in the nonfatal heart attack of an Idaho postal worker. Then, in December, a federal judge in Houston declared a mistrial after a jury could not decide if a Florida man’s monthlong use of the drug led to his fatal heart attack.
Most of the plaintiffs claim that Merck knew of Vioxx’s potential danger long before recalling the drug but did not act on concerns so they could keep the profitable drug on the shelves. The company claims it did not act irresponsibly and disclosed its research on the drug.
The third case heard in Texas is set in 259th state District Judge Alex Gabert’s courtroom. Garza’s case could take a month to present all the evidence to the jury, according to the family’s attorneys, the McAllen law firm of Hockema, Tippit & Escobedo.
They claim the company has tried to stall the case, originally set for trial Feb. 14, 2005, employing state legislators with law practices to file continuances and asking that a federal judge hear the case.
"Merck has done everything in its power to deny the Garza family their day in court. This included two remands to federal court and the hiring of multiple state representatives for the sole purpose of stalling this trial," said Joe Escobedo Jr., a lead attorney representing the Garza family.
"We look forward to representing the Garza family and exposing Merck’s greed and corruption in relation to Vioxx."
In January, state Sen. Juan "Chuy" Hinojosa, D-McAllen, entered Merck’s defense team for one day and the company filed a motion of legislative continuance, allowing the trial to stall until after the session ended. However, the next day, Hinojosa withdrew that motion, claiming Merck’s lawyers never told him that they had planned to file a motion of continuance. Hinojosa said he did not read the affidavit he signed attached to the motion and later withdrew from the case.
The next day, the company hired Rep. Rene Oliveira, D-Brownsville, and filed a second legislative continuance. Oliveira is a partner in the Brownsville law firm of Roerig, Oliveira & Fisher LLP and originally joined the defense team as lead counsel.
However, on Dec. 5, Merck filed a motion adding Ricardo Cedillo of the San Antonio firm Davis, Cedillo & Mendoza as lead counsel.
Oliveira said he is actively participating in the case and preparing for trial.
"We’re confident that any fair jury will find that Merck and the product Vioxx had nothing to do with the unfortunate passing of Mr. Garza," Oliveira said.
Merck’s defense team includes Baldemar Garza in Rio Grande City and Houston lawyer Richard Josephson of Baker & Botts.

Expert Opinion on Drug Safety Launches an Open-Access Correspondence Section

2006-01-09T06:17:00.000-08:00

LONDON, January 6 /PRNewswire/ -- Since the withdrawal of Vioxx, issues surrounding drug safety, adverse events and pharmacovigilance have become more important than ever, leading to a plethora of debate and discussion regarding drug safety issues. The fine balance between benefit and risk means that there are many differing opinions from experts spanning different disciplines including pharmacology, clinical medicine, pharmacoeconomics and regulatory affairs. Over the last year, Expert Opinion on Drug Safety has seen an increase in the amount of feedback received. To accommodate this, the journal has launched a correspondence section, in which readers can address issues arising from reviews published in the journal. This correspondence section also allows the author to reply, thus stimulating interesting debate - an important forum for discussion.
According to Dr John Barrett, Senior Director - Infectious Diseases, Merck Research Laboratories, "Expanding the journal with the addition of a correspondence section has enhanced the journal's impact by providing for lively and timely exchange of opinion."
All letters published in the correspondence section are freely available online at www.ashley-pub.com/eds.
Published six times a year, Expert Opinion on Drug Safety seeks to unravel the vast amount of drug safety information and provide clear and informed guides. Each article contains an 'Expert Opinion' section, in which authors are encouraged to express their personal opinion on the status of the research under review.
About Expert Opinion
For over a decade, the Expert Opinion series has provided systematic and authoritative reviews to support every stage of the drug discovery and R&D pipeline from target to market. Each of the nine journals in the series covers a specific aspect of the pharmaceutical pipeline.
The series contains the following journals: Expert Opinion on Biological Therapy, Expert Opinion on Drug Metabolism & Toxicology, Expert Opinion on Drug Safety, Expert Opinion on Emerging Drugs, Expert Opinion on Investigational Drugs, Expert Opinion on Pharmacotherapy, Expert Opinion on Therapeutic Patents, and Expert Opinion on Therapeutic Targets.
New for June 2006 - Expert Opinion on Drug Discovery
This new addition to the Expert Opinion range will focus on drug discovery in the post-genomic era, with particular emphasis on the technologies and disciplines involved; assay development, modelling, in silico drug design and informatics.

Genetics Plays Role in Side Effects Associated With Painkillers

2006-01-09T06:16:00.000-08:00

A study published in the January issue of the American Gastroenterological Association (AGA) journal Gastroenterology found a difference in how people responded to popular painkillers and that up to 30 percent of this variability can be attributed to an individual’s genetic makeup. This variation can influence both how useful the drugs are in affording relief from pain and inflammation, and the number and severity of the adverse effects. This evaluation is perhaps the most rigorous look at how people vary in their response to drugs and was designed as part of a strategy to determine genetic and other markers that might help predict response and safety of these drugs, including susceptibility to cardiovascular complications.
The study looked at people taking two popular painkillers --rofecoxib (Vioxx, Merck) and celecoxib (Celebrex, Pfizer) -- known as COX-2 inhibitors. During the past two years, evidence has emerged that COX-2s confer a risk of heart attack and stroke, resulting in two of the drugs in this class being withdrawn from the market and a black box warning being issued for a third drug.
“The use of any drug involves a mix of benefits and risks. The problems with COX-2 inhibitors were real, but involved less than 2 percent of patients who were taking them,” said Garret A. FitzGerald, MD, study author from the University of Pennsylvania School of Medicine. “Because we often underestimate just how much people differ in their response to the same dose of the same drug, there is a need to develop diagnostic methods to identify those patients at an increased risk of cardiovascular events and explore this variability in drug response to move toward an individualized approach in drug development.”
Researchers at the University of Pennsylvania examined the variability, both within and between subjects, in response to celecoxib and rofecoxib, in a randomized, double-blind, placebo controlled study. Screening, enrollment and follow-up of healthy study volunteers was performed between January 2002 and January 2004. The study was conducted on 50 healthy volunteers between the ages of 21 and 43 years old who received a single dose of placebo, celecoxib and rofecoxib in random order. This was done to allow researchers a direct comparison of the responses to the drugs within the same subjects. Five of the patients went through the entire protocol five times to assess variability within individuals.
According to study authors, different factors in the environment result in a variety of responses from an individual who is dosed with the same drug at different times. This effect is seen even when as many variables as possible are standardized or controlled for. Approximately 30 percent of the variability found in patients was attributable to differences between individuals, suggesting the contribution of genetics to a variety of biomarkers of drug response. The study also illustrates that even healthy individuals without a recognized risk of disease respond quite differently to the drugs.
Previous studies have shown that rofecoxib and celecoxib result in a small number of the people who were apparently at a low-risk of cardiovascular disease initially, proceeding to increase that risk to the point that culminates in heart attack and stroke following prolonged use of these drugs. According to researchers, exploiting this variability could permit management of the cardiovascular risk of COX-2 inhibitors, while preserving their efficacy for patients most likely to benefit from them and determining how these drugs might be administered to people initially at low risk for cardiovascular disease.
“Typically when a drug causes hazardous side effects, the reaction is to suggest that people reduce the dosage they are taking. However, this has often been followed by withdrawal of the drug from the market when the problems are not eliminated,” said FitzGerald. “These findings highlight that while a lower dose may reduce the likelihood of problems on average, it will not eliminate them on an individual level because there is such a marked variability in how each person reacts to these drugs based on their genetic makeup.”
Study authors are hopeful that this work will provide an impetus for the development of a science-based approach to risk management. Exploitation of variability in response can lead to tests that identify patients most likely to benefit or suffer from harmful side effects caused by these drugs. “This study provides a starting point for the development of diagnostics that allow the medical and research communities to conserve benefits while managing the risks of COX-2 inhibitors,” said FitzGerald.
About the AGAThe American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology.
About Gastroenterology Gastroenterology, the official journal of the AGA, is the most prominent journal in the subspecialty and is in the top one percent of indexed medical journals internationally.
Source: American Gastroenterological Association

Truth in advertising; service packaging; 'tingi' marketing

2006-01-09T06:15:00.000-08:00

QUESTION: If consumer perception is the primary basis for getting people to buy products and services, does this mean that truth in advertising is irrelevant in marketing?
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Answer: On the contrary, what this means is that marketers ought to be extra careful in using consumer perception to motivate consumers through advertising.
As a marketer, you can use consumer perceptions for good or bad. Truth in advertising is good. Deception is bad. You can get away with it at first, but it won't last.
Consumers will, sooner or later, find out that they've been fooled. As Abraham Lincoln said: "You can fool some of the people some of the time. But you can't fool all of the people all the time."
Deception, of course, includes cases of keeping quiet about what you know may harm consumers. That's a case of withholding "truth."
Take the case of Merck's Vioxx, the acute pain killer and anti-arthritis medication that had to be withdrawn from the market because Merck, or more precisely its medical researchers, withheld from publication in the New England Journal of Medicine knowledge of three heart attacks among Vioxx's patients participating in the large scale clinical study of Vioxx.
The heart attacks took place in the final five weeks of the trial study. The patients who had the heart attack were supposedly at low risk for heart problems.
But this was not the only thing the Merck researchers withheld. The study had apparently found "more cardiovascular problems potentially connected to Vioxx."
These problems were not reported in the published study. Such withholding of knowledge is highly unethical and a serious breach of the Hippocratic oath.
In pharmaceutical marketing, published clinical studies are a powerful "advertising" material for persuading doctors, such that withholding knowledge of the three heart attacks and the connection to more cardiovascular problems violated the truth in advertising maxim.
Question: Your column mentioned that the consumers' first physical contact with a consumer product is not with the product itself, but the packaging. That's why you said it's critical to give packaging more than the passing attention it's given. How about in the case of services? Where is the first physical contact?
Answer: Think of consumer goods packaging as the product's tangible presentation at point of purchase. So let's rephrase your question into: "For a service, what is the tangible presentation at point of purchase?"
We've written before that a service is intangible. To give it a tangible presentation, you need (in the words of Ted Levitt of Harvard) to "tangibilize its intangibles." How do you do that?
Experts in service marketing say that service is presented to customers through three things: (1) a satisfying service staff, (2) a satisfying service venue, and (3) a satisfying service processing.
So there you are. A service packaging has three dimensions that you must all satisfy simultaneously.
It is because of this inseparable, multi-dimensional character of services that marketers like to say that service marketing is much more difficult than consumer goods marketing.
Notice that one of the three dimensions of service packaging involves a human being. That's not at all easy to control in terms of consistent quality.
Question: In "tingi" marketing, or low-unit pack/sachet marketing, how do you determine the right size to offer?
Answer: This is one of those marketing problems where you cannot go wrong if you go by the "marketing concept."
It's that concept that says: "Always start from where your consumers are and never from where you (as marketers) are." So find out what your target consumers' preference is. Or look around for a benchmark. Consider, for example, shampoo.
The size of its sachet is a single-use amount for its target consumer, the amount of which has been validated by a product test.
Or take cheddar cheese, the low unit pack of which is a single slice.
The size and thinness was determined largely by moms of school kids bringing cheese sandwiches.
Or take the latest mega users of "tingi," namely, Smart Communications Inc. (which pioneered it) and Globe Telecom Inc. (which followed suit after six months).
Both of these marketers have applied the low unit pack on SMS, the phone's so-called "killer application" and its "pasa load."
That "pasa" [transfer] load's tingi started with P5 and based on continuing consumer demand, has now gone down to the unbelievable pasa load amount of P2!
So the key to answering your question are your target consumers. Consult them. Learn from them.

Merck Vioxx Judge Threatens to End Suit Consolidation (Update2)

2006-01-09T06:14:00.000-08:00

The judge overseeing federal lawsuits over Merck & Co.'s Vioxx painkiller said he may end his effort to combine the cases for a possible settlement because of delays in getting some claims to trial.
U.S. District Judge Eldon Fallon in New Orleans said he is having trouble getting jury trials scheduled after Hurricane Katrina displaced thousands of residents and shut the city's courthouses for months. Plaintiffs' lawyers are pressing ahead with similar Vioxx suits in state courts around the U.S.
Fallon, at a Jan. 3 hearing, said he may ``shut down'' the consolidation ``if all the cases are being tried in state court before we get one tried in federal court.''
The judge said he will consider sending all federal Vioxx cases back to their home states for trial, a move that would make it more difficult to negotiate an overarching settlement. Merck, the third-largest U.S. drugmaker, has refused to pursue a settlement and instead set aside $675 million to fight suits over claims that Vioxx caused heart attacks or strokes.
``Judge Fallon is trying to make the point that he wants to see the federal litigation stay on track,'' said Ted Mayer, a lawyer with New York's Hughes Hubbard & Reed who represents Merck. ``The only way to do that is to press forward with getting cases to trial.''
Test Cases
Fallon said in October he wanted to try some Vioxx claims before starting settlement talks. Fallon had set three federal cases for trial in the first four months of this year, with plans to use the verdicts to help set values for other Vioxx claims.
``They were supposed to be test cases,'' said Chris Seeger, a New York lawyer with the firm of Seeger Weiss and a member of a steering committee overseeing the federal cases. ``If Judge Fallon can't try them, then his only choice is to get them ready for trial and farm them back out.''
Six Vioxx suits are set for trial in state courts in New Jersey, Texas, Florida and California over the next six months, Fallon said. Getting the same number of federal cases scheduled in New Orleans in the period will be difficult because of the devastation wreaked by the August storm and floods, he said.
``The witnesses are not available, the lawyers are not available, the records are not available and the doctors are not available,'' Fallon said.
Merck, based in Whitehouse Station, New Jersey, pulled Vioxx off the market in September 2004 after studies linked it to increased heart risks for long-term users. In February, a panel ordered all federal Vioxx suits consolidated in Fallon's court for pre-trial proceedings. Judges sometimes use consolidations to push for settlements in product-liability cases.
Split Verdicts
Merck's shares fell 31 cents to $32.87 in after-hours trading and have fallen more than 26 percent since Vioxx's withdrawal. The drug generated $2.5 billion in sales in 2004.
Fallon has estimated the company may have to defend more than 100,000 Vioxx suits. Merck's liability may reach $50 billion, Friedman Billings Ramsey analyst David Moskowitz estimates.
The company split the first three cases tried over the painkiller. In August, a Texas state court jury ordered Merck to pay $253 million to the family of a Wal-Mart manager who died of heart problems after taking Vioxx for about eight months.
A state jury in Atlantic City, New Jersey ruled in November that Merck wasn't responsible for the heart attack of a postal worker who took the drug for about two months. In December, a federal jury in Houston deadlocked over whether a Florida man's use of the drug for about a month led to his fatal heart attack. The case is set to be tried again in February.
Mark Lanier, a Houston attorney who won the first Vioxx verdict against Merck, said the company's vow to try all suits over the painkiller is forcing plaintiffs' lawyers to pursue state court trials. Lanier is set to try the next one, in New Jersey starting Feb. 27.
``I have 2,000 Vioxx cases that I need to get to trial,'' Lanier said. ``If there are problems with getting them tried in federal court, I have to move forward in all possible courts.''