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The power of phase II end-points for different possible mechanisms of action of an experimental treatment

Lookup NU author(s): Professor James WasonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2015 The Authors.Background The high failure rate in phase III oncology trials is partly because the signal obtained from phase II trials is often weak. Several papers have considered the appropriateness of various phase II end-points for individual trials, but there has not been a systematic comparison using simulated data to determine which end-point should be used in which situation. Methods In this paper we carry out simulation studies to compare the power of several Response Evaluation Criteria in Solid Tumours (RECIST) response-based end-points for one-arm and two-arm trials, together with progression-free survival (PFS) and testing the tumour-shrinkage directly for two-arm trials. We consider six scenarios: (1) short-term cytotoxic therapy; (2) continuous cytotoxic therapy; (3 + 4) cytostatic therapy; (5 + 6) delayed tumour-shrinkage effect (seen in some immunotherapies). We also consider measurement error in the assessment of tumour size. Results Measurement error affects the type-I error rate and power of single-arm trials, and the power of two-arm trials. Generally no single end-point performed well in all scenarios. Best observed response rate, PFS and directly testing the tumour-shrinkages performed best for a number of scenarios. PFS performed very poorly when the effect of the treatment was short-lived. In scenario 6, where the delay in effect was long, no end-point performed well. Conclusions A clinician setting up a phase II trial should consider the likely mechanism of action the drug will have and choose an end-point that provides high power for that scenario. Testing the difference in tumour-shrinkage is often powerful. Alternative end-points are required for therapies with a long delayed effect.

Publication metadata

Author(s): Wason JMS, Dentamaro A, Eisen TG

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 2015

Volume: 51

Issue: 8

Pages: 984-992

Print publication date: 01/05/2015

Online publication date: 31/03/2015

Acceptance date: 04/03/2015

Date deposited: 26/01/2018

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

Publisher: Elsevier Ltd


DOI: 10.1016/j.ejca.2015.03.002

PubMed id: 25840669


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