Increasing FDA-accelerated approval of single-arm trials in oncology (1992 to 2020)

We aimed to map the characteristics of single-arm trials (SAT), report the Food and Drug Administration (FDA) transparency in presenting historical control, and to assess the confirmatory randomized controlled trials (RCTs).

This metaresearch included a review of all oncology indication approved using SAT by FDA-AA (FDA-Accelerated Approval) from 1992 to 2020. Two independent reviewers identified SAT, extracted data from FDA full medical reviews for historical controls reported and MEDLINE for searching for confirmatory RCT published.

Of 254 FDA-AA approvals, 119 (47%) were approved for oncologic indications using SAT. Fifty-four drugs for 72 oncology indications were for leukemia, lymphoma, lung cancer, urothelial cancer, multiple myeloma, and thyroid cancer. Overall, 37 (52%) treatments were converted into regular approval. Of these, 17 (46%) were based on confirmatory RCTs using overall survival (OS) as an outcome. Five indications were withdrawn from the market. Most trials outcomes were blindly assessed by independent research committees. Median trial sample size was 105 patients (min:8 to max:532). The FDA did not fully specify historical control selection in 75% of cases.

The granting of FDA-AAs based on SAT in oncology is increasing with more target drugs approved over time. Transparency in historical control reporting is necessary.