Clinical trial designs incorporating predictive biomarkers
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Updated: Mar 26, 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
Lindsay A Renfro1, Himel Mallick2, Ming-Wen An3
1Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
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.
Insights
Traditional cancer trials are evolving. Novel clinical trial designs are crucial for targeted oncology therapies, especially when analyzing patient biomarkers and treatment response in diverse cancer populations.
Area of Science:
- Oncology
- Clinical Trial Design
- Biostatistics
Background:
- Traditional cancer therapy development relied on sequential trials (Phase I-III) in homogeneous patient groups.
- Molecular understanding of cancer necessitates new trial designs for targeted therapies and biomarker-driven treatments.
- Existing designs struggle to address the complexity of personalized cancer medicine.
Purpose of the Study:
- To review the literature on clinical trial designs for targeted cancer agents.
- To explore designs accommodating patient subgroups defined by biomarkers or genetic mutations.
- To discuss real-world applications, advantages, and challenges of biomarker-based trial designs.
Main Methods:
- Literature review of clinical trial design methodologies.
- Analysis of proposed and existing biomarker-driven trial designs.
- Case studies of implemented biomarker-based trials in oncology.
Main Results:
- Identified a range of innovative trial designs beyond traditional phase I-III structures.
- Highlighted the utility of biomarker-based designs for targeted therapies.
- Discussed practical considerations and limitations encountered in real-world applications.
Conclusions:
- Biomarker-driven clinical trial designs are essential for advancing targeted cancer therapies.
- Novel designs are needed to match the increasing stratification of cancer based on individual patient and tumor characteristics.
- Continued innovation in trial design is critical for the future of precision oncology research.
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