Drug Safety at the FDA Under Fire: What to Do?

Criticism of FDA's Drug Safety Efforts Triggers Debate

Aside from criticizing the FDA for not acting sooner to protect Americans from the potential risks associated with Vioxx, Graham also warned that five additional popular prescription drugs should be closely monitored due to safety concerns. Graham fingered Crestor, Bextra, Meridia, Serevent, and Accutane in his statement…. During his testimony, Graham, who is an associate science director at the FDA's Office of Drug Safety, said that the recommendations of drug safety reviewers are often overruled by officials in the FDA's Office of New Drugs. He asked lawmakers to create an independent drug safety monitoring office free of the influence from regulators who approve new drugs.

But Galson says the FDA's Office of New Drugs is already an independent office and is separate from the office that reviews drug safety. Both offices report to Galson, as the acting director of the Center for Drug Evaluation and Research.

To address post-approval drug safety concerns, Galson says he recently asked the Institute of Medicine (IOM) to look at the structure of the FDA's post-marketing surveillance program and to give their advice on whether additional changes are needed to the agency's approach to drug safety.

This is a bureaucratic response, one which before all else defends the agency.  That leaves us with two concerns:  (1) is the IOM an independent, credible agency, and (2) is it likely that their recommendations if critical of the existing structure will be implemented?  The answer to the first is a qualified yes, for it is funded by Congress, and as for (2).  There are too many political loops to jump including a President who is in bed with the pharmaceutical industry, as is Congress, and Galson will surely oppose a review system outside the FDA, for bureaucrats always defend their turf.   Finally studies are the do-something, do-nothing dodge.  In a couple of years a report will be generated by the IOM and reviewed, and by that time Congress, the President, and the public will have forgotten the cause for the study.  Skepticism is further reinforced by the track record of the FDA, which has consistently been pro-pharameutical industry.  The chances for significant in the public’s interest action is slim, while the pretend concern and pretend we are doing something has already started.  History is repeating itself. 

Vioxx May Have Caused 140,000 Heart Attacks


Jan 26 '05

Food and Drug Administration safety reviewer David Graham estimates that Merck's Vioxx may have caused as many as 140,000 heart attacks in the U.S. before it was withdrawn last September. His estimate was published in the British medical journal Lancet.

The study was based on records of 1.4 million members of Kaiser Permanente, the largest U.S. nonprofit insurer, with 6 million members in California. Many of the cases may have been fatal, Graham said.

A Merck spokesman said the estimate of harm from Vioxx was "speculation." Determinations of Vioxx's potential role in patients' cardiovascular problems "can only be made on a case by case basis," he said.

The publication of Graham's findings is expected to intensify the drug-safety debate that has swept Washington since the Vioxx withdrawal. Graham and other critics accuse the FDA of being too slow to ban or tighten regulations on medicines that cause serious side effects.

Researchers compared the incidence of heart attacks and sudden cardiac death for patients taking Vioxx with those on Pfizer's Celebrex, a similar painkiller, and over-the-counter medications.

Applying the findings across the U.S. population, "We arrived at the estimate of 88,000 to 140,000 patients that had a heart attack in the U.S. because they used Vioxx" after it was introduced in 1999, Graham said.

Portions of the study had been disclosed earlier. Graham said in Nov. 18 testimony before the Senate Finance Committee that between 88,000 and 139,000 heart attacks may have been linked to Vioxx.

Merck withdrew Vioxx after a company study showed that patients taking it for 18 months or longer had twice the risk of heart attacks and strokes -- 1.5 percent -- as those taking a placebo.

Graham said his bosses at the FDA at one point threatened to fire him as associate director for science and medicine in the agency's Office of Drug Safety if he published the findings.

The study found that Vioxx, given at the standard dose, increases the risk of heart attack by about 50 percent, compared with Pfizer's Celebrex, and more than triples the risk of heart attacks when given at high doses. The two drugs suppress the body's production of the Cox-2 enzyme, which is linked to pain and swelling.

People taking Vioxx had a 34 percent higher chance of heart disease compared with those taking other painkillers including Celebrex, naproxen and ibuprofen, the study found.

Patients taking naproxen, a generic painkiller sold as Aleve by Bayer AG, had a 14 percent increase in heart risk compared with some other painkillers such as ibuprofen, the study showed. Previous trials had suggested naproxen may protect against cardiac disease.