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Review
. 2016 Feb;43:74-82.
doi: 10.1016/j.ctrv.2015.12.008. Epub 2016 Jan 5.

Clinical Trial Designs Incorporating Predictive Biomarkers

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Free PMC article
Review

Clinical Trial Designs Incorporating Predictive Biomarkers

Lindsay A Renfro et al. Cancer Treat Rev. .
Free PMC article

Abstract

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research.

Keywords: Adaptive trial design; Bayesian adaptive design; Biomarker-based design; Clinical trial design; Enrichment designs; Targeted therapies.

Conflict of interest statement

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Schemas for biomarker-driven designs: (A) enrichment design; (B) biomarker-by-treatment interaction design; (C) multi-target, multi-agent biomarker strategy design; (D) adaptive enrichment design; (E) biomarker design with response-adaptive randomization; (F) umbrella trial; and (G) basket trial.
Fig. 1
Fig. 1
Schemas for biomarker-driven designs: (A) enrichment design; (B) biomarker-by-treatment interaction design; (C) multi-target, multi-agent biomarker strategy design; (D) adaptive enrichment design; (E) biomarker design with response-adaptive randomization; (F) umbrella trial; and (G) basket trial.

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