The FDA has compiled 22 case studies — including for two medical devices — that showed promise in Phase II clinical trials but later failed in larger Phase III trials.
The agency restated the importance of maintaining large, randomized, controlled trials, although the industry is increasingly interested in using alternatives to expensive Phase III trials and in using surrogate endpoints for accelerated results.
Despite good results at the Phase II stage for one device, Broncus Technologies’s Exhale drug-eluting stent, used to improve airflow in patients with emphysema, in Phase III the stent failed to improve lung function or symptoms, the FDA said.
The report also cited the Co-Star drug-eluting coronary stent. A small clinical study conducted outside the U.S. suggested that it performed as well as other marketed stents. However, a clinical trial of 1,700 patients in the U.S. to support an application for FDA approval showed a significantly higher rate of cardiac problems at eight months compared with other stents.
Fourteen of the 22 studies were unable to confirm effectiveness, one was unable to confirm safety, and seven were unable to confirm both safety and effectiveness, the agency found. Two Phase III studies found an increased frequency of the problem the product intended to prevent.
“Phase III trials help care providers understand when a medical product provides clinical benefit to patients that outweigh the risks,” the FDA said. “They also help researchers understand when a purported mechanism of action is credible and merits further development.”