Friday, October 20, 2006

Vioxx Suits Surge to Beat Deadline -

Vioxx Suits Surge to Beat Deadline - "Vioxx Suits Surge to Beat Deadline
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"

Wednesday, May 03, 2006

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

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, 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 (, 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

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

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.''

Tuesday, May 02, 2006

No Defense For This Insanity

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

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

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.” (
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 (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

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 ...

Friday, April 07, 2006

Merck & Co. Is Losing Ground Following Vioxx Ruling

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

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

Tuesday, April 04, 2006

Health News Article |

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

Monday, April 03, 2006

Doctor says Vioxx didn't kill man

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

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.