Oncology drug approvals in the United States are increasingly supported by single-arm clinical trials, according to a study published in JAMA Oncology.

Researchers noted that this change has advantages, such as facilitating patient access to novel therapies, but it also comes with limitations that must be considered.

The researchers evaluated the role of single-arm trials in oncology drug approvals by the US Food and Drug Administration (FDA) between January 1, 2002, and December 31, 2021. 

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During that time, the FDA approved 563 new oncology drug indications, and 176 (31%) of those approvals were based on data from single-arm trials. The researchers noted a substantial increase in approvals supported by single-arm trials in the years 2017-2021 compared with previous years.

Of the approvals based on single-arm trials, 87 (49%) were for novel agents, and 89 (51%) were for supplemental indications. A total of 60 (34%) approvals were made through traditional means and 116 (66%) by accelerated approval. 

Post-marketing requirements were fulfilled for 45 (38%) indications granted accelerated approval, and 61 (52%) indications required further verification of benefit. Ten (9%) accelerated approvals were ultimately revoked.

The researchers noted that the benefits of single-arm trials include a shorter completion time, a smaller sample size requirement, and the ability to detect efficacy signals early in development. 

“In the appropriate context, single-arm trials using durable RRs [response rates] can allow patients expedited access to novel therapies,” the researchers wrote.

They added, however, that limitations of single-arm trials include difficulty distinguishing the contribution of effect for multiple drugs, attribution of adverse events, difficulties in optimizing dose selection, and challenges with using historical controls.

“While SATs [single-arm trials] continue to demonstrate their use as a valuable tool to evaluate and approve cancer therapies, RCTs [randomized controlled trials] remain the preferred approach in clinical investigation and are the preferred design to support the approval of new anticancer therapies,” the researchers concluded.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Agrawal S, Arora S, Amiri-Kordestani L, et al. Use of single-arm trials for US Food and Drug Administration approval in oncology, 2002-2021. JAMA Oncol. Published online December 29, 2022. doi:10.1001/jamaoncol.2022.5985