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.
Keywords
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Article info
Publication history
Published online: December 09, 2008
Accepted:
October 29,
2008
Received:
October 17,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
