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Updated: Jun 21, 2026
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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
Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges
Sumithra J Mandrekar1, Daniel J Sargent
1Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. mandrekar.sumithra@mayo.edu
Summary
Biomarker-guided therapy improves patient treatment by integrating tumor genetics and patient genotype. Evaluating clinical trial designs, such as retrospective and prospective methods, accelerates the validation of these personalized medicine strategies.
Area of Science:
- Biomarker discovery and validation
- Clinical trial design
- Personalized medicine
Background:
- Biomarkers integrate tumor genetics and patient genotype for personalized treatment.
- Biomarker-guided therapy offers substantial value in medical practice.
Purpose of the Study:
- To discuss and evaluate various clinical trial designs for validating biomarker-guided therapy.
- To guide patient-specific treatment selection through genetic profiling.
Main Methods:
- Classification of predictive marker validation designs into retrospective and prospective approaches.
- Evaluation of salient features of each design within real-world clinical trials.
- Discussion of enrichment, unselected, hybrid, and adaptive analysis designs.
Main Results:
- Retrospective analyses from RCTs can expedite effective treatments for marker-defined subgroups (e.g., KRAS in colorectal cancer).
- Enrichment designs are suitable when treatment benefit is marker-dependent (e.g., trastuzumab in breast cancer).
- Unselected designs are optimal for uncertain treatment benefit or assay reproducibility (e.g., EGFR in lung cancer).
- Hybrid designs address ethical concerns when a subgroup shows clear efficacy (e.g., multigene assays in breast cancer).
- Adaptive analysis allows prespecified subgroup analyses within RCTs.
Conclusions:
- Implementation of these design strategies will accelerate the clinical validation of biomarker-guided therapy.
- Optimized trial designs are crucial for the successful integration of biomarkers into clinical practice.
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