The FDA compiled 22 case studies of different drugs, vaccines and devices that demonstrated promising results in Phase II studies, but later failed in larger Phase III clinical trials.
The agency restated the importance of maintaining the gold standard — large, randomized, controlled trials — while interest grows in using alternatives to expensive Phase III trials, and in incorporating surrogate endpoints for accelerated results.
Fourteen studies were unable to confirm effectiveness, one was unable to confirm safety, and seven were unable to confirm both. Two Phase III studies demonstrated an increased frequency of the problem the product intended to prevent. Additionally, six products were already FDA approved in another indication during the Phase III trial.