Related Experiment Video

Updated: Oct 27, 2025

Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
07:35

Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances

Published on: October 11, 2018

7.7K

A Problematic Biomarker Trial Design

Boris Freidlin1, Edward L Korn1

  • 1Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.

Journal of the National Cancer Institute
|July 21, 2021
PubMed

Insights

Biomarker-driven clinical trials are crucial for precision oncology. However, current phase III designs may incorrectly recommend treatments to biomarker-negative patients who do not benefit.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Biostatistics

Background:

  • Precision oncology relies on biomarker-driven clinical trials for targeted therapies.
  • Current phase III trial designs often evaluate treatments in both biomarker-positive and overall populations.
  • This broad evaluation can lead to suboptimal treatment recommendations.

Purpose of the Study:

  • To highlight potential limitations in common biomarker-driven phase III trial designs.
  • To address the risk of recommending ineffective treatments to biomarker-negative patients.
  • To encourage the development of more refined trial methodologies.

Main Methods:

  • Review of standard biomarker-driven phase III clinical trial designs.
  • Analysis of treatment effect evaluation across different patient subgroups (biomarker-positive vs. overall).
  • Identification of scenarios where current designs may lead to inappropriate treatment recommendations.

Main Results:

  • Common phase III designs test treatment efficacy in biomarker-positive and overall populations.
  • This approach can mask a lack of benefit in biomarker-negative subgroups.
  • Treatments may be recommended to biomarker-negative patients despite no demonstrated efficacy.

Conclusions:

  • Existing biomarker-driven phase III trial designs may not adequately protect biomarker-negative patients from ineffective treatments.
  • There is a need for more precise trial designs that specifically assess treatment effects within biomarker-defined subgroups.
  • Refined methodologies are essential for the responsible implementation of precision oncology.

More Related Videos

Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis07:40

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

17.5K
Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies07:20

Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies

Published on: January 28, 2014

36.8K

Related Concept Videos

Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs01:15

Bioequivalence Experimental Study Designs: Repeated Measures, Cross-Over, Carry-Over, and Latin Square Designs

Body:Bioequivalence experimental study designs play a pivotal role in testing the effectiveness of various treatments. Key among these are the repeated measures, cross-over, carry-over, and Latin square designs. In the repeated measures design, each subject receives all treatments, allowing for temporal comparisons. This type of design is useful in reducing variability but requires careful planning to avoid bias.The cross-over design, an economical method, involves sequential administration of...
42
Bioavailability Study Design: Healthy Subjects Versus Patients01:15

Bioavailability Study Design: Healthy Subjects Versus Patients

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,...
28
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

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,...
209
Bioequivalence Experimental Study Designs: Completely Randomized and Randomized Block Designs01:20

Bioequivalence Experimental Study Designs: Completely Randomized and Randomized Block Designs

Body:Bioequivalence experimental study designs are crucial methodologies used in evaluating and comparing the bioavailability of different drug products. These designs are categorized into various types: completely randomized, randomized block, repeated measures, cross and carry-over, and Latin square designs.Completely randomized designs involve randomly allocating treatments to all subjects participating in the experiment. This allocation is achieved by assigning unique random numbers to...
38
Bioavailability Study Design: Single Versus Multiple Dose Studies01:11

Bioavailability Study Design: Single Versus Multiple Dose Studies

Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
43
Crossover Experiments01:16

Crossover Experiments

Crossover experiments, also called the repeated-measurements design, is a study design in which all experimental units are exposed to all treatments in different periods. Crossover experiments are generally used in psychology, the pharmaceutical industry, agriculture, and medicine.
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.
4.1K