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# FDA Discussion Paper Looks at Clinical Trial Failures
- URL: https://www.fdaweb.com/fda-discussion-paper-looks-at-clinical-trial-failures/
- Published: 2017-01-20T12:00:00.000Z
- Updated: 2026-09-14T22:01:57.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5137789

FDA has released a [discussion paper](http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM535780.pdf?ref=fdaweb.com) entitled “22 Case Studies Where Phase 2 and Phase 3 Trials Had Divergent Results” to illustrate the challenges drug developers face and why about nine out of 10 drugs/biologics tested are never submitted for approval. The paper acknowledges the growing interest in recent years in exploring alternatives to requiring Phase 3 testing before product approval, such as relying on different types of data and unvalidated surrogate endpoints.

Of the 22 examples, 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,” FDA says. “In two cases, the Phase 3 studies showed that the experimental product increased the frequency of the problem it was intended to prevent. This paper is not intended to assess why each of these unexpected results occurred or why further product development was not pursued. Rather, these cases, chosen from a large pool of similar examples, illustrate the ways in which controlled trials of appropriate size and duration contribute to the scientific understanding of medical products.”

  
The 22 cases explored in the paper also demonstrate that Phase 2 results can inaccurately predict safety or effectiveness for medical products, FDA concludes. “These cases also help illustrate the potential public health implications of undue reliance on Phase 2 studies and the benefits of conducting Phase 3 studies,” it says. “As a result of the Phase 3 studies discussed in this paper, patients outside of clinical trials were not subjected to drugs that would not benefit them or to the risk of unnecessary serious toxicities, and did not suffer unnecessary financial expenditures.”