Avandia Heart Study Raises Questions About Reliability of Results

The results of a large clinical study of Avandia’s heart side effects, which was paid for by the drug’s maker, GlaxoSmithKline, PLC, has come under intense criticism for using bad science.

The RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes) study, which was released last week and published in the medical journal Lancet, was touted as showing that Avandia side effects do not increase the risk of a heart attack.

Critics of the report, which include physicians, the FDA and Avandia attorneys representing plaintiffs who have filed a lawsuits against GlaxoSmithKline, say that the methodology of the study is flawed, with too small a sample size and researchers knowing which subjects were on what medication. In addition, the study involved the use of Avandia together with other drugs and 40% of the subjects actually stopped taking Avandia before the research was completed.

Avandia (rosiglitazone) is a type 2 diabetes drug approved by the FDA in 1999. It is a thiazolidinedione agent, which acts by increasing the body’s sensitivity to insulin and aiding in the management of blood sugar in diabetics.

Nearly a dozen other studies, including some by GlaxoSmithKline P.L.C., have indicated that the side effects of Avandia may increase the risk of heart attacks, congestive heart failure, liver failure, bone fractures, macular edema and death.

One May 2007 meta-analysis of 42 clinical studies published in the New England Journal of Medicine, found that users faced a 43% increase in the risk of a heart attack on Avandia.

The FDA required that a “black box” warning be placed on Avandia in November 2007, indicating that the drug could increase the risk of heart attacks. However, the consumer advocacy group Public Citizen petitioned the FDA last year to issue an Avandia recall, indicating that the drug should not even be available, as any potential benefits provided by the medication are outweighed by the side effects.

The FDA denounced the RECORD study’s science two years ago, and GlaxoSmithKline has already started another study, known as TIDE, in response to FDA’s criticisms.

Last year, the American Diabetes Association (ADA) recommended against using Avandia. However, ADA officials say they will review the RECORD study’s results and determine whether they may change their recommendations.

GlaxoSmithKline PLC currently faces hundreds of lawsuits over Avandia heart risks filed by uses who suffered heart attacks, congestive heart failure and other cardiovascular injuries. All federal cases have been consolidated in an MDL, or Multidistrict Liigation, centralized in the Eastern District of Pennsylvania before U.S. District Judge Cynthia Rufe. The first Avandia lawsuit is scheduled for trial to begin early next summer.