Nearly two years earlier, on March 15, 2000, Dr. John Buse, an Associate Professor of Medicine and Director of a Diabetes Care Center in Durham, North Carolina, sent a letter to then FDA Commissioner, Dr Jane Henney, warning the FDA about the risks of Avandia and describing the abuse of clinical trial data by Glaxo.
"I remain concerned about the safety of rosiglitazone," Dr Buse wrote, "in light of its consistent negative impact on lipids documented in the FDA registration data as well as a worrisome trend in cardiovascular deaths and severe adverse events in the subjects exposed to rosiglitazone versus active comparators."
Dr Buse warned, "I think the FDA has to act forcefully to prevent the rampant abuse of clinical trial data by SmithKline Beecham."
He warned Dr Henney that Glaxo was overstating the safety of Avandia with respect to cardiovascular issues. "I have been shown glossy materials claiming that rosiglitazone has been uniquely studied in patients with preexisting cardiac disease," he wrote, "including patients with a number of associated conditions (such as unstable angina)."
"I know for a fact," he noted, "that such patients are excluded in clinical trials as I am a PI [Principal Investigator] in one of their trials."
Lawmakers in both Houses of Congress reacted to the news of another FDA regulatory failure immediately. On May 21, 2007 the US House of Representatives Committee on Oversight and Government Reform announced that a hearing would be held on June 6, 2007, at 10:00 am in Room 2154, Rayburn House Office Building, to assess the FDA's role in the evaluation of the safety of Avandia.
Committee chairman, Rep Henry Waxman (D-CA) extended an invitation to the author of the NEJM article, cardiologist, Dr Steven Nissen of the Cleveland Clinic, to testify at the hearing and discuss his article.
Dr Nissen and statistician Kathy Wolski, MPH, evaluated 42 studies involving nearly 28,000 patients and compared the 15,560 patients who were using Avandia to the patients who were not using the drug. The study found there were 86 myocardial infarctions in the Avandia group and 72 in the control group and there were 39 deaths from cardiovascular causes in Avandia patients compared to 22 in the control group.
Rep Waxman also sent a letter to FDA Commissioner Andrew von Eschenbach requesting his testimony at the hearing. In addition, he instructed the Commissioner to provide the Committee with specific information from August 1, 2005, to the present to include: (1) A chronology of actions taken by FDA in relation to the cardiovascular safety of rosiglitazone; (2) All communications between GlaxoSmithKline and the FDA relating to cardiovascular safety of rosiglitazone; and (3) All internal FDA analyses, slide presentations, and memoranda relating to the cardiovascular safety of rosiglitazone.
"In complying with this request," Rep Waxman advised the Commissioner, "you should produce all responsive documents in your possession, custody, or control."
Rep Waxman also told the Commissioner, "you should submit a written certification, signed by you or your counsel, stating that: (1) a diligent search has been completed of all documents in your possession, custody, or control which reasonably could contain responsive documents: and (2) all documents located during the search that are responsive have been produced to the Committee or identified in a privilege log."
And last but not least, Rep Waxman sent a letter to Glaxo CEO, Dr Jean-Pierre Garnier, asking him to appear. "We request that you come prepared to discuss your company's actions with regard to the cardiovascular safety of Avandia," the letter states.
Over in the US Senate, Senators Max Baucus and Chuck Grassley, Chairman and Ranking Member of the Senate Committee on Finance, which has jurisdiction over the Medicare and Medicaid programs, issued a public statement and sent letters to the FDA and Glaxo demanding they provide specific documents and other information to the Committee.
"What we are learning about the handling of Avandia," Sen Baucus said in the statement, "by both GlaxoSmithKline and the FDA is appalling and unacceptable."
"Both the drug company and the FDA," he said, "have some major explaining to do about what they knew about Avandia, when they knew it, and why they didn't take immediate action to protect patients."
"We need to know if this is another Vioxx," Senator Grassley stated, "where the FDA sat on its hands and endangered lives."
Must Read (
Well Said (
News (
Touching (
Funny (
Supported (
Interesting (
Inspiring (
Valuable (
