JAMA Article Looks at Data-Sharing in Clinical Trials for Heart Disease

How and when to share clinical trial data for heart studies - including when to suspend a study - is vitally important to physician-scientists and regulators as an increasing number of clinical trials evaluate new treatments. This issue is explored in the April 9 Journal of the American Medical Association (JAMA) in a commentary article authored by Dr. Jeffrey S. Borer of NewYork-Presbyterian Hospital/Weill Cornell Medical Center and Drs. David J. Gordon and Nancy L. Geller - both of the National Heart, Lung and Blood Institute (NHLBI).

Treatment decisions are based on findings from scientific studies called clinical trials that can sometimes involve many thousands of patients. Several of these studies - such as those involving the drugs Avandia, Vytorin and, earlier, Vioxx - have been the subject of recent controversies in the media.

Increasingly, clinical trials are monitored by independent, external groups called Data and Safety Monitoring Committees (DSMCs), charged with protecting the safety of trial participants and preserving trial integrity and credibility. These committees are the only groups that can know results of blinded trials (trials in which participants and investigators are not aware of treatment assignments) while the trials are ongoing. The proper function of DSMCs is subject to discussion and debate. The JAMA article addresses one aspect of this debate.

"Several situations exist in which it is reasonable and appropriate for the DSMC to share interim data from a blinded trial with operational study personnel and sponsors. These situations might include the need for 'mid-course corrections,' when the number of outcome events - like deaths and heart attacks - is substantially lower in the untreated group than was expected in a trial to reduce such problems," says Dr. Jeffrey S. Borer, article co-author and director of Cardiovascular Pathophysiology and co-director of The Howard Gilman Institute for Valvular Heart Diseases at NewYork-Presbyterian/Weill Cornell, and the Gladys and Roland Harriman Professor of Cardiovascular Medicine at Weill Cornell Medical College.

"If this happens," Dr. Borer continues, "the total number of patients slated to participate in the trial may be inadequate to test the therapy's effectiveness. In this case, the DSMC might notify the sponsor and suggest an increase in the number of subjects to be recruited into the study. However, the DSMC would not tell the sponsor the number of events that had occurred in each treatment group."

While sharing some data would be reasonable and appropriate in several other situations, Dr. Borer stresses that "the DSMC should share patient treatment assignments related to interim outcome/event data with the sponsor in only one situation - when recommending premature termination of the study."

Reasons the DSMCs recommend termination include:
* The committee perceives a rising toll of adverse events that appears to outweigh any possible benefit from the treatment.