Document Detail

Randomized phase II designs.
MedLine Citation:
PMID:  19276275     Owner:  NLM     Status:  MEDLINE    
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.
Larry Rubinstein; John Crowley; Percy Ivy; Michael Leblanc; Dan Sargent
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Publication Detail:
Type:  Journal Article; Review     Date:  2009-03-10
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-17     Completed Date:  2009-04-16     Revised Date:  2013-09-23    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1883-90     Citation Subset:  IM    
National Cancer Institute, Bethesda, Maryland, USA.
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MeSH Terms
Clinical Trials, Phase II as Topic / methods*
Neoplasms / drug therapy*,  mortality
Randomized Controlled Trials as Topic / methods*
Research Design*
Grant Support
U10 CA038926/CA/NCI NIH HHS; U10 CA038926-23/CA/NCI NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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