Assessing Drug Efficacy After Multiple Negative Trials—Gepirone’s Journey Through the FDA

This case study traces how the antidepressant gepirone ER won FDA approval in 2023 on just 2 positive trials out of 13, after four prior rejections and a negative advisory committee vote. The authors argue this reflects the FDA’s reliance on “trial counting” and statistical over clinical significance, and that the label compounds the problem by omitting the 11 negative trials. FDA should report all efficacy trials and an overall effect size in labeling so clinicians can better assess a drug’s clinical benefit.