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. 2011 Dec;1(12):1629-1636.
doi: 10.4155/CLI.11.152.

Design of clinical trials for biomarker research in oncology

Sumithra J Mandrekar  1 , Daniel J Sargent
Affiliations

Design of clinical trials for biomarker research in oncology

Sumithra J Mandrekar et al. Clin Investig (Lond). 2011 Dec.

Abstract

The developmental pathway from discovery to clinical practice for biomarkers and biomarker-directed therapies is complex. While several issues need careful consideration, two critical issues that surround the validation of biomarkers are the choice of clinical trial design (which is based on the strength of the preliminary evidence and marker prevalence) and the biomarker assay related issues surrounding the marker assessment methods such as the reliability and reproducibility of the assay. This review focuses on trial designs for marker validation, both in the setting of early phase trials for initial validation, as well as in the context of larger definitive trials. Designs for biomarker validation are broadly classified as retrospective (i.e., using data from previously well-conducted, randomized, controlled trials) or prospective (enrichment, allcomers or adaptive). We believe that the systematic evaluation and implementation of these design strategies are essential to accelerate the clinical validation of biomarker-guided therapy, thereby taking us a step closer to the goal of personalized medicine.

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Figures

Figure 1
Figure 1
Design of N0923, a Phase II trial following an enrichment strategy. SCLC: Small-cell lung cancer.
Figure 2
Figure 2
Design of N0577, a Phase III trial following an enrichment strategy. RT: Radiation therapy; TMZ: Temozolomide.
See this image and copyright information in PMC

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