WASHINGTON — A June 6 congressional hearing on the approval process and oversight of rosiglitazone found members of Congress pointing accusatory fingers at almost everyone who testified, including officials from the Food and Drug Administration, the company producing the drug, and the scientist who published a study expressing concerns about the drug's cardiovascular effects.
Rep. Henry Waxman (D-Calif.), chairman of the House Committee on Oversight and Government Reform, set the tone for the hearing in his opening statement. “It is not Congress' role to adjudicate these medical issues,” he declared. “But it is our role to ensure that the Food and Drug Administration is taking these concerns seriously and providing doctors and patients with the guidance they need to make informed decisions.”
Committee member Darryl Issa (R-Calif.) fired back, questioning the need for the hearing. “I'm concerned that we not tread too closely toward the hypocrisy this hearing begins to look like,” he said. “Politicizing science is what we could be doing here today.”
The hearing was held 3 weeks after Dr. Steven Nissen of the Cleveland Clinic and his colleague, Kathy Wolski, published a meta-analysis in the online edition of the New England Journal of Medicine suggesting that type 2 diabetes patients taking rosiglitazone had a 43% higher risk of myocardial infarction (MI) compared with patients on other drug treatments. (See story, p. 1.)
The day before the congressional hearing, the journal published interim results from the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial, which looked at hospitalization or death from cardiovascular causes. The authors concluded that “the data were insufficient to determine whether the drug was associated with an increase in the risk of myocardial infarction” (Epub doi: 10.1056/NEJMoa073394). Three accompanying editorials all suggested that such a risk warranted careful consideration of the drug's use.
At the hearing, Rep. Waxman questioned FDA Commissioner Dr. Andrew von Eschenbach about why the agency did not take seriously the concerns of one of its own medical reviewers at the time the drug was approved.
Although the drug achieved the purpose of lowering blood sugar in patients with type 2 diabetes, “the increase in body weight and undesirable effects on serum lipids is cause for concern … It cannot be assumed that treatment with rosiglitazone will decrease the risk” of heart disease, according to the FDA's medical review dated April 1999. The reviewer recommended that a postmarketing study be done to address those concerns.
Dr. von Eschenbach defended the agency's actions, noting that the FDA has been monitoring cardiovascular adverse events, including edema and heart failure, since rosiglitazone was approved. He also said that rosiglitazone's label was updated in April 2006 to include new warnings about a potential increase in MIs in heart failure patients.
Dr. von Eschenbach noted that the agency was still analyzing follow-up data that it has received, and that it has scheduled an advisory committee meeting for July 30 to discuss whether additional action needs to be taken.
Rep. Issa admonished Dr. Nissen for his failure to share his findings with the FDA prior to publication. “You didn't even give them the benefit of the doubt,” Rep. Issa said.
Dr. Nissen responded that the FDA had access to all the data he had and added that submitting findings for peer review and publication was standard scientific practice.
Dr. John Buse, president-elect of the American Diabetes Association and director of the Diabetes Care Center at the University of North Carolina, Chapel Hill, testified that he first raised the issue of rosiglitazone's cardiovascular side effects in 1999. Dr. Buse said that officials at SmithKline Beecham—the predecessor to GlasxoSmithKline—then tried to intimidate him, implying that he could be held personally liable for the $4-billion drop in the company's value that occurred after his concerns became widely known.
In response to a question from Rep. Waxman about the “shocking” way Dr. Buse was treated, Moncef Slaoui, Ph.D., chairman of research and development at GSK, said that “there was a lot of passion on his side and on the side of the [company's] scientists” regarding the issue of rosiglitazone's safety. “We regret that Dr. Buse felt pressured.”
Dr. Steven Nissen of the Cleveland Clinic testifies at a congressional hearing on the oversight of Avandia. Jay Westcott/Elsevier Global Medical News