Congress Questions Vioxx, FDA

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• MARGARET WARNER:

  Now, what went wrong in the case of the blockbuster painkiller Vioxx? That's what members of Congress wanted to know at a hearing today. Susan Dentzer, of our health unit, has a report. The unit is a partnership with the Henry J. Kaiser Family Foundation.

• SUSAN DENTZER:

  Today's Senate Finance Committee hearing on Vioxx opened with scathing comments about the Food and Drug Administration, and about Merck, Vioxx's manufacturer. Iowa Republican Charles Grassley is the committee's chairman.

• SEN. CHARLES GRASSLEY:

  Today's witnesses will describe how danger signals were ignored. They will offer perspective on how appropriate action was not taken. We'll see that the FDA failed to heed the words of even its own scientists. It also looks like the FDA allowed itself to be manipulated by Merck.

• SUSAN DENTZER:

  Merck took its blockbuster painkiller off the market in September after its own study showed a doubling in the risk of heart attack and stroke. Dr. David Graham is an official of FDA's Office of Drug Safety; he was one of several witnesses who told lawmakers the episode constituted an unprecedented failure of the nation's system of drug approval and oversight.

• DR. DAVID GRAHAM:

  Vioxx has been a disaster. This is unparalleled in the history of the United States.

• SUSAN DENTZER:

  Graham then offered an estimate of the scope of the debacle in terms of the number of Americans who took Vioxx and then experienced additional heart attacks and strokes.

• DR. DAVID GRAHAM:

  This estimate ranges from 88,000 to 139,000 Americans. Of these, 30 to 40 percent probably died. Now, imagine that we were talking about jetliners. If there were an average of 150 to 200 people on an aircraft, this range of 88,000 to 139,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky. This translates to two to four aircraft every week– week in, week out– for the past five years.

• SUSAN DENTZER:

  But the top FDA official present, Dr. Sandra Kweder, took strong issue with both Grassley's and Graham's assessments, and especially with Graham's calculations about Vioxx's overall health impact.

• DR. SANDRA KWEDER:

  First of all, these are not real deaths. The data on deaths are… as Dr. Graham himself said, are something you figure out on a spreadsheet; they're a mathematical model that is made up, that is put together with a number of assumptions along the way. We do utilize such mathematical models to help guide how we study drugs and to a certain extent make some decisions about them, but one has to be extremely cautious.

• SUSAN DENTZER:

  Kweder also argued that those estimates ignored the benefits of Vioxx; it's one of a class of painkillers specifically designed to avert potentially fatal stomach and intestinal problems. Kweder pointed out these so- called gastrointestinal or GI benefits of Vioxx had not been found in two other drugs Vioxx competed with– Pfizer's Celebrex and Bextra.

• DR. SANDRA KWEDER:

  What seems to have been lost in a lot of the discussion of Vioxx is that this drug remained the only non-steroidal anti- inflammatory that had a clear- cut GI safety benefit. It's the only one. You can't just look at the cardiovascular risks of this drug. One has to look at the full spectrum of risks and potential benefits.

• SUSAN DENTZER:

  Much of today's hearing focused on what Merck knew about the cardiovascular risks of Vioxx and when it knew it. Several witnesses argued that Merck knew as long ago as 1996 that the drug could produce cardiovascular problems. Dr. Bruce Psaty is a University of Washington epidemiologist.

• DR. BRUCE PSATY:

  In November 1996, and I draw your attention to exhibit three, Merck scientists hypothesized patients taking Vioxx would have higher rates of heart disease than those taking an aspirin-like comparison. By April 1998 Merck scientists knew Vioxx not only lacks the anti-platelet effects of aspirin, but it also disables one of the body's defenses against the blood vessels' clumping of platelets. On the basis of this biologic evidence, it would be reasonable to hypothesize that compared to the placebo Vioxx treatment if it might increase the risk of heart attack and stroke. For Vioxx to be used safely in millions of patients, the potential cardiovascular risks need to be defined clearly.

• SUSAN DENTZER:

  Dr. Psaty and other witnesses also accused Merck of designing its Vioxx studies so that results would highlight the drug's benefits and downplay the cardiovascular risks. Merck's chief executive officer, Ray Gilmartin, denied that.

• RAYMOND GILMARTIN:

  Merck puts patients first. Mr. Chairman, Merck believed wholeheartedly in Vioxx; I believed wholeheartedly in Vioxx. In fact, my wife was taking Vioxx, using Vioxx up until the day we withdrew it from the market.

• SUSAN DENTZER:

  Gilmartin specifically denied that data the company had in 1996 amounted to compelling evidence of cardiovascular risks.

• RAYMOND GILMARTIN:

  Discussions that they referred to in 1996 about the design of trials was well before there was even a theoretical expectation that there could be a cardiovascular risk with the Cox-2 class. There was not even a theory at that point.

• SUSAN DENTZER:

  And Gilmartin argued that when red flags about Vioxx were directly raised through Merck's own studies in 2000, the company pursued them vigorously.

• RAYMOND GILMARTIN:

  We relentlessly pursued additional studies. We monitored this drug for cardiovascular safety. Whenever we found out data, whether unfavorable or favorable, we disclosed it to the public promptly, and we continue to study the drug in order to find the answer.

• SUSAN DENTZER:

  Lawmakers pressed the witnesses about the need for changes in drug regulation and oversight to prevent future drug disasters. Max Baucus of Montana is the Finance Committee's ranking Democrat.

• SEN. MAX BAUCUS:

  Does the FDA have sufficient resources, authority, and independence to ensure that the drugs it approves are safe? And should it be doing more to monitor drug safety after a drug has been approved?

• SUSAN DENTZER:

  Most witnesses agreed far more needed to be done. They especially urged more monitoring of drugs intended for long-term use after those drugs come on the market.

• SPOKESMAN:

  The FDA should reorient priorities and devote more attention and resources to patient safety. Specific proactive post- marketing trials or studies should be designed, conducted, and completed in a timely fashion.

• SUSAN DENTZER:

  Grassley asked about separating two FDA offices involved in new drug approvals and drug safety. Witnesses like Graham had argued that their safety concerns were too often overruled by FDA officials who had been involved in approving those same drugs.

• SEN. CHARLES GRASSLEY:

  It doesn't make sense from an accountability standpoint to have the office that reviews the safety of drugs that are already on the market to be under the thumb of the office that puts the drugs on the market in the first place.

• SUSAN DENTZER:

  The FDA's Kweder agreed that making the safety office independent was an idea worth considering.

• DR. SANDRA KWEDER:

  We understand that there are concerns by the members of the Congress, by the public, about how sound our system is, and we look forward to change, if that's what is deemed needed.

• SUSAN DENTZER:

  Lawmakers promised to continue exploring the Vioxx case and the prospect of regulatory overhaul when the new Congress convenes in January.