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

Published version
Peer-reviewed

Change log

Authors

Mossop, Helen 
Grayling, Michael J  ORCID logo  https://orcid.org/0000-0002-0680-6668
Gallagher, Ferdia A  ORCID logo  https://orcid.org/0000-0003-4784-5230

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.

Description

Funder: RCUK | MRC | Medical Research Foundation; doi: https://doi.org/10.13039/501100009187


Funder: NIHR Biomedical Research Centre BRC-1215-20014

Keywords

Adaptive Clinical Trials as Topic, Clinical Trials, Phase II as Topic, Cohort Studies, Computer Simulation, Humans, Medical Oncology, Neoplasms, Non-Randomized Controlled Trials as Topic, Research Design, Sample Size, Treatment Outcome

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

126

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MR/T024097/1)
Cancer Research UK (C96/A25177)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Cancer Research UK Cambridge Centre [C9685/A25177]