Adaptive Biomarker-Based Design for Early Phase Clinical Trials
Alessandra Serra1, Gaëlle Saint-Hilary2, Sandrine Guilleminot3
1University of Cambridge, MRC Biostatistics Unit, Cambridge, UK.
Statistics in Medicine
|October 9, 2025
Summary
This study introduces a biomarker-guided clinical trial design for early-phase oncology studies. The adaptive approach improves decision-making by refining patient populations based on predictive biomarkers, even with limited sample sizes.
Area of Science:
- Clinical trial design
- Biomarker discovery
- Oncology research
Background:
- Precision Medicine relies on identifying predictive biomarkers for patient stratification.
- Early phase adaptive trial designs enhance efficiency through in-trial modifications.
- Current designs may miss efficacy signals in biomarker-defined subgroups.
Purpose of the Study:
- To propose a novel one-arm, two-stage, early-phase biomarker-guided design.
- To enable adaptive decisions at interim analysis for population refinement.
- To improve efficacy signal detection in biomarker subgroups.
Main Methods:
- Development of a two-stage, one-arm adaptive design.
- Incorporation of interim analysis for population selection/enrichment.
- Simulation studies to evaluate design performance.
Main Results:
- The proposed biomarker-guided design enhances decision-making in early phase trials.
- It offers advantages over classical designs lacking biomarker enrichment.
- Effective even with limited sample sizes, it aids in identifying efficacy signals.
Conclusions:
- Biomarker-guided adaptive designs are valuable for early-phase oncology trials.
- This approach optimizes patient selection and improves the chances of detecting efficacy signals.
- It represents a significant advancement for patient-centric clinical development.
Related Concept Videos
01:11Clinical Trials: Overview
4.5K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.5K
01:28Preclinical Development: Overview
5.7K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.7K
01:16Clinical Trials
10.1K
Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
There are four phases in a clinical trial. A phase one...
10.1K
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
126
Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
126
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
375
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
375
01:28Structure-Activity Relationships and Drug Design
1.6K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.6K