The Validation of Surrogate End Points by using Data from Randomized Clinical Trials: A Case-Study in Advanced Colorectal Cancer

Abstract
Summary: In many therapeutic areas, the identification and validation of surrogate end points is of prime interest to reduce the duration and/or size of clinical trials. Buyse and co-workers and Burzykowski and co-workers have proposed a validation strategy for end points that are either normally distributed or (possibly censored) failure times. In this paper, we address the problem of validating an ordinal categorical or binary end point as a surrogate for a failure time true end point. In particular, we investigate the validity of tumour response as a surrogate for survival time in evaluating fluoropyrimidine-based experimental therapies for advanced colorectal cancer. Our analysis is performed on data from 28 randomized trials in advanced colorectal cancer, which are available through the Meta-Analysis Group in Cancer.

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