Optimising the design of phase II oncology trials: the importance of randomisation

Eur J Cancer. 2009 Jan;45(2):275-80. doi: 10.1016/j.ejca.2008.10.029. Epub 2008 Dec 6.

Abstract

Oncology trial end-points continue to receive considerable attention, as illustrated by the development and revisions to the RECIST criteria. In this article, we focus the reader away from the issue of end-points for phase II trials and towards what we believe to be an even more important issue, the fundamental need for randomisation in phase II oncology trials, ideally with blinding and dose-ranging. We present arguments to support the proposition that randomisation will enable greater clarity in the interpretation of the phase II trial results, as well as allowing for more precise estimates of the effect size and sample size requirements for definitive phase III trials. Randomisation will also reduce potential bias resulting from inter-trial variability, which inflates both type I and II errors if historical controls are utilised. In the context of a randomised blinded trial, the exact choice of end-point is less critical, although we favour end-points such as the change in tumour size or progression status at a fixed early time point (i.e. 8-12 weeks after randomisation). Although end-points based on RECIST criteria can and should be utilised in randomised phase II trials, we do not believe that revision of the RECIST criteria will result in a fundamental improvement in drug development decisions in the absence of randomised clinical trials at the phase II stage of drug development.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic / methods*
  • Clinical Trials, Phase II as Topic / standards
  • Humans
  • Neoplasms / drug therapy*
  • Observer Variation
  • Random Allocation
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / standards
  • Research Design
  • Sample Size
  • Treatment Outcome

Substances

  • Antineoplastic Agents