TY - JOUR
T1 - Optimising the design of phase II oncology trials
T2 - The importance of randomisation
AU - Ratain, Mark J.
AU - Sargent, Daniel J.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Clinical trial design
KW - Phase II
KW - Randomization
UR - http://www.scopus.com/inward/record.url?scp=57849154374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57849154374&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2008.10.029
DO - 10.1016/j.ejca.2008.10.029
M3 - Article
C2 - 19059773
AN - SCOPUS:57849154374
SN - 0959-8049
VL - 45
SP - 275
EP - 280
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 2
ER -