FDA review hampered by the ghost of Vioxx

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

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

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

How a law firm races to repair its Vioxx files

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