Document Detail

Randomized phase III clinical trial designs for targeted agents.
MedLine Citation:
PMID:  18628448     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Cancer therapies with mechanisms of action which are very different from the more conventional chemotherapies are now being developed. In this article, we investigate the performance of several phase III clinical trial designs, both for testing the overall efficacy of a targeted agent and for testing its efficacy in a subgroup of patients with a tumor marker present. We study different designs and different underlying scenarios assuming continuous markers, and assess the trade-off between the number of patients on the study and the effectiveness of treatment in the subgroup of marker-positive patients.
EXPERIMENTAL DESIGN: We investigate binary outcomes and use simulation studies to determine sample size and power for the different designs and the various scenarios. We also simulate marker prevalence and marker misclassification and evaluate their effect on power and sample size.
RESULTS: In general, a targeted design which randomizes patients with the appropriate marker status performs the best in all scenarios with an underlying true predictive marker. Randomizing all patients regardless of their marker values performs as well as or better in most cases than a clinical trial that randomizes the patient to a treatment strategy based on marker value versus standard of care.
CONCLUSION: If there is the possibility that the new treatment helps marker-negative patients, or that the cutpoint determining marker status has not been well established and the marker prevalence is large enough, we recommend randomizing all patients regardless of marker values, but using a design such that both the overall and the targeted subgroup hypothesis can be tested.
Antje Hoering; Mike Leblanc; John J Crowley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  14     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-16     Completed Date:  2008-09-16     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4358-67     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / administration & dosage*
Clinical Trials, Phase III as Topic*
Drug Delivery Systems*
Neoplasms / drug therapy*
Randomized Controlled Trials as Topic
Research Design*
Tumor Markers, Biological
Grant Support
CA090998/CA/NCI NIH HHS; R01 CA090998/CA/NCI NIH HHS; R01 CA090998-01/CA/NCI NIH HHS
Reg. No./Substance:
0/Antineoplastic Agents; 0/Tumor Markers, Biological

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