FDA Emphasizes Need for Phase III Clinical Trials

A report issued by the FDA noted discrepancies between phase II and phase III drug trials, emphasizing the need for appropriate – and sometimes lengthy – review of drugs and mature clinical trial data. The FDA’s report also cautioned against assumptions about the accuracy of phase II studies, which can be “misleading” and potentially harmful to the public.

There has been growing interest in exploring alternatives to requiring phase III testing prior to product approval. However, in the FDA’s research, based on 22 case studies of drugs, vaccines, and medical devices since 1999, promising phase II clinical trial results were not confirmed in phase III clinical testing. Fourteen of these cases did not confirm efficacy, one did not confirm safety, and seven confirmed neither. In addition, two cases showed in phase III trials that the product increased the frequency of the problem it was intended to prevent.

According to the report, “These unexpected results could occur even when the phase II study was relatively large and … assessed clinical outcomes. Phase II results can inaccurately predict safety and/or effectiveness for medical products in a wide range of diseases and patient populations. … These cases also help illustrate the potential public health implications of undue reliance on phase II studies and the benefits of conducting phase III studies.”

To read the FDA report, visit fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM535780.pdf.

Source: U.S. Food and Drug Administration report, “22 Case Studies Where Phase 2 and Phase 3 Trials Had Divergent Results,” January 2017.