Single-arm clinical trials that supported FDA Accelerated Approvals have modest effect sizes and at high risk of bias
Single-arm trials that informed treatment approval by the FDA-AA have modest effect sizes
The lower bound of the 95% CI of 53% of approved treatments crossed the line of null effect
The effect sizes were not larger in the studies that were followed by the FDA-required confirmatory randomized trials
: To describe effect sizes of single-arm clinical trials that supported AA approvals. Study desing and Setting: We reviewed all the single-arm approvals granted by the FDA-AA pathway between June1992 to December2020. Two independent reviewers identified single-arm studies and extracted data from FDA Full-Medical Reviews. We performed a meta-analysis to estimate the effect sizes and compared it between studies that met post-approval FDA requirements for RCTs with those that did not.
: From the total of 254 approvals, single arm clinical trials describing effects of 54 drugs for 72 clinical indications were evaluated. The effect size estimated was OR:2.22(CI95%:1.76-2.81)[relative risk(RR)=1.63(95CI% 1.38-1.92)]; 53% of treatments had a lower 95% CI bound crossing the null effect. Effect size did not differ between the treatments that met the FDA requirement for conducting post-approval RCTs.
Conclusions and Relevance
: Treatment effects observed in the FDA AA single-arm studies was modest and can be to ascribed to bias.