Avandia Heart Attack Concerns May Be Scaring Away Test Subjects

GlaxoSmithKline is apparently having real trouble recruiting potential test subjects for a controversial clinical trial due to concerns about the risk of heart attacks from Avandia, resulting in several sites withdrawing from the study.

The study, known as TIDE (Thiazolidinedione Intervention in Vitamin D Evaluation), is designed to compare the heart risks of Avandia with Actos, a competing type 2 diabetes drug manufactured by Takeda Pharmaceuticals. According to a report in the Wall Street Journal, at least two sites have been closed recently due to an inability to convince people to take part in the clinical trials.

In recent months, there have been calls from consumer advocates and researchers for the FDA to halt the Avandia study, suggesting that it is unethical and dangerous for the trials to continue given the known risk of Avandia heart attacks and other side effects.

In April, FDA Commissioner Margaret Hamburg sent a letter to U.S. Senator Charles Grassley indicating that the agency is considering shutting down the comparative study over concerns about the ethics of continuing the trial. Many have speculated that if the FDA deems exposing clinical subjects to potential Avandia heart problems unethical, it will likely lead to an Avandia recall for the same reasons.

One of the sites that recently withdrew from the study, located at Wake Forest University Baptist Medical Center, in North Carolina, was closed after a year-long recruiting effort was determined to be “not succeeding in recruiting anybody,” according to Wake Forest Medical Center Dean William Applegate.

In response, Glaxo has opened new sites in developing nations such as Pakistan, India, Latvia, Columbia and others. This raises additional concerns about the ethics of the study, as the drug maker appears to be focusing their recruiting efforts in places where people may not have heard about the possible side effects of Avandia.

Avandia (rosiglitazone) was approved in the United States in 1998 to treat type 2 diabetes by helping control blood sugar levels. The drug has been used by millions of diabetics, but sales have plummeted in recent years in the United States as concerns have mounted about the risk of serious and potentially life-threatening heart risks. Some experts estimate that Avandia has caused between 60,000 and 200,000 heart attacks and deaths due to cardiovascular problems in the U.S. from 1999 to 2006.

Concerns about the risk of Avandia problems first gained widespread attention in the United States in May 2007, when a meta-analysis of 42 different clinical trials was published in the New England Journal of Medicine, suggesting that users of Avandia had a 43% increased risk of a heart attack. In the wake of the study, FDA ordered Glaxo to perform the TIDE trial.

Earlier this year, a Senate report was released that criticized GlaxoSmithKline for intimidating doctors who spoke out about Avandia side effects and for failing to adequately warn users about the risk of a heart attack from side effects of Avandia. In addition, at a House drug safety hearing earlier this month, several lawmakers pressed FDA with questions on why such a recall of Avandia has not yet occurred.

Glaxo currently faces thousands of Avandia lawsuits filed by former users who allege that they suffered heart failure, heart attacks and other injuries as a result of side effects of the drug. While the drug maker has previously taken a firm stance in defense of their type 2 diabetes medication, and indicated that they would defend against injury cases at trial, it has been reported that the drug maker agreed to settle Avandia lawsuits brought by about 700 people for $60 million, which comes to around $86,000 per plaintiff.