Considerations for Single-Arm Trials to Support Accelerated Approval of Oncology Drugs

TL;DR

This paper clarifies when single-arm trials are appropriate for accelerated approval of oncology drugs, outlining necessary and sufficient conditions, and providing guidance for study design and regulatory communication.

Contribution

It introduces a comprehensive set of conditions for designing and interpreting single-arm trials in the context of accelerated approval, aiding regulatory decision-making.

Findings

Identifies two necessary conditions for SAT design.

Defines three sufficient conditions for optimizing SATs.

Proposes four conditions to demonstrate clinical benefits.

Abstract

In the last two decades, single-arm trials (SATs) have been effectively used to study anticancer therapies in well-defined patient populations using durable response rates as an objective and interpretable clinical endpoints. With a growing trend of regulatory accelerated approval (AA) requiring randomized controlled trials (RCTs), some confusions have arisen about the roles of SATs in AA. This paper is intended to elucidate conditions under which an SAT may be considered reasonable for AA. Specifically, the paper describes (1) two necessary conditions for designing an SAT, (2) three sufficient conditions that help either optimize the study design or interpret the study results, (3) four conditions that demonstrate substantial evidence of clinical benefits of the drug, and (4) a plan of a confirmatory RCT to verify the clinical benefits. Some further considerations are discussed to help design a scientifically sound SAT and communicate with regulatory agencies. Conditions presented in this paper may serve as a set of references for sponsors using SATs for regulatory decision.