Advantages of multi-arm non-randomised sequentially allocated cohort designs for Phase II oncology trials

Br J Cancer. 2022 Feb;126(2):204-210. doi: 10.1038/s41416-021-01613-5. Epub 2021 Nov 8.

Abstract

Background: Efficient trial designs are required to prioritise promising drugs within Phase II trials. Adaptive designs are examples of such designs, but their efficiency is reduced if there is a delay in assessing patient responses to treatment.

Methods: Motivated by the WIRE trial in renal cell carcinoma (NCT03741426), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. The MASTER design recruits patients to one arm at a time, pausing recruitment to an arm when it has recruited the required number for an interim analysis. We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms.

Results: The parallel multi-arm multi-stage and the MASTER design are much more efficient than separate trials. The MASTER design provides extra efficiency when there is endpoint delay, or recruitment is very quick.

Conclusions: We recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in non-comparative Phase II trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Clinical Trials as Topic / methods*
  • Clinical Trials, Phase II as Topic / methods*
  • Cohort Studies
  • Computer Simulation / standards*
  • Humans
  • Medical Oncology / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Non-Randomized Controlled Trials as Topic / methods*
  • Research Design / standards*
  • Sample Size
  • Treatment Outcome