Multistage adaptive biomarker-directed targeted design for randomized clinical trials

Contemporary Clinical Trials
Zhong GaoMing Tan

Abstract

Precision medicine is changing how patients are treated and how therapies are developed. In recent years, biomarker-directed targeted designs have been developed for pharmaceutical development aimed at patient subpopulation with a specific disease etiology. To integrate multistage testing into the targeted designs enhances flexibility of targeted trials by enabling sequential monitoring and stochastic curtailment. We studied a multistage adaptive design for targeted trials with either normally distributed endpoint or binary endpoint. The design is based on the fact that distribution of the sequence of test statistics from multistage testing is asymptotically well approximated by a Brownian motion in targeted trials with normally distributed continuous endpoint or binary endpoint. This study has demonstrated that the targeted multistage design improves study efficiency, information accumulation and conditional power as compared with its untargeted counterpart. Furthermore, our study has indicated that biomarker performance plays a crucial role in efficiency and effectiveness of the multistage adaptive design. The sensitivity and specificity of a biomarker used for patient enrichment influence level of heterogeneity of the target...Continue Reading

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Citations

Feb 2, 2016·Cancer Treatment Reviews·Lindsay A RenfroSumithra J Mandrekar
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Oct 8, 2020·The International Journal of Biostatistics·Hongbin ZhangMing T Tan

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