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Updated: Jun 17, 2026

Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis
Published on: March 20, 2021
Randomized clinical trials with biomarkers: design issues
Boris Freidlin1, Lisa M McShane, Edward L Korn
1Biometric Research Branch, EPN-8122, National Cancer Institute, Bethesda, MD 20892, USA. freidlinb@ctep.nci.nih.gov
Abstract:
Clinical biomarker tests that aid in making treatment decisions will play an important role in achieving personalized medicine for cancer patients. Definitive evaluation of the clinical utility of these biomarkers requires conducting large randomized clinical trials (RCTs). Efficient RCT design is therefore crucial for timely introduction of these medical advances into clinical practice, and a variety of designs have been proposed for this purpose. To guide design and interpretation of RCTs evaluating biomarkers, we present an in-depth comparison of advantages and disadvantages of the commonly used designs. Key aspects of the discussion include efficiency comparisons and special interim monitoring issues that arise because of the complexity of these RCTs. Important ongoing and completed trials are used as examples. We conclude that, in most settings, randomized biomarker-stratified designs (ie, designs that use the biomarker to guide analysis but not treatment assignment) should be used to obtain a rigorous assessment of biomarker clinical utility.
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