To better understand the nature of the evidence obtained from many phase 2 trials and the contributions of phase 3 trials of drugs, vaccines and medical devices, FDA studied 22 recent cases in which promising phase 2 clinical trial results were not confirmed in phase 3 clinical testing. Phase 3 studies did not confirm phase 2 findings of effectiveness in 14 cases, safety in one case, and both safety and effectiveness in seven cases. These unexpected results could occur even when the phase 2 study was relatively large and even when the phase 2 trials assessed clinical outcomes.
These case studies demonstrate that large phase 3 randomized controlled trials can generate critical evidence across all types of products, patients, and diseases. Both safety and efficacy failures occurred even when the phase 2 studies were relatively large, and even when the product was already approved for another condition. In some cases, the phase 3 study revealed that short-term results found in the phase 2 study were not associated with a long-term benefit or that the product had toxicity that was not uncovered in the phase 2 study.