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Randomized phase II designs.

Rubinstein, Larry and Crowley, John and Ivy, Percy and Leblanc, Michael and Sargent, Dan (2009) Randomized phase II designs. Clinical cancer research : an official journal of the American Association for Cancer Research, 15 (6). pp. 1883-1890. ISSN 1078-0432

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As the use of molecularly targeted agents, which are anticipated to increase overall survival (OS)and progression-free survival (PFS) but not necessarily tumor response, has increased in oncology, there has been a corresponding increase in the recommendation and use of randomized phase II designs. Such designs reduce the potential for bias, existent in comparisons with historical controls, but also substantially increase the sample size requirements. We review the principal statistical designs for historically controlled and randomized phase II trials, along with their advantages, disadvantages, and statistical design considerations. We review the arguments for and against the use of randomization in phase II studies, the situations in which the use of historical controls is preferred, and the situations in which the use of randomized designs is preferred. We review methods used to calculate predicted OS or PFS values from historical controls, adjusted so as to be appropriate for an experimental sample with particular prognostic characteristics. We show how adjustment of the type I and type II error bounds for randomized studies can facilitate the detection of appropriate target increases in median PFS or OS with sample sizes appropriate for phase II studies. Although there continue to be differences among investigators concerning the use of randomization versus historical controls in phase II trials, there is agreement that each approach will continue to be appropriate, and the optimal approach will depend upon the circumstances of the individual trial.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above for the first 12 months following publication.
DOI: 10.1158/1078-0432.CCR-08-2031
PubMed ID: 19276275
Grant Numbers: U10 CA038926
Keywords or MeSH Headings: Clinical Trials, Phase II as Topic/methods; Humans; Neoplasms/drug therapy/mortality; Randomized Controlled Trials as Topic/methods; Research Design;
Depositing User: Library Staff
Date Deposited: 09 Feb 2010 18:53
Last Modified: 14 Feb 2012 14:42

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