Related Experiment Video
Updated: May 7, 2026
08:58
Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow
Published on: October 17, 2025
Adaptive enrichment with subpopulation selection at interim: methodologies, applications and design considerations.
Sue-Jane Wang1, H M James Hung
1Office of Biostatistics, OTS/CDER, FDA, Silver Spring, MD 20993, USA.
Contemporary Clinical Trials
|October 1, 2013
Summary
Adaptive enrichment strategies in drug development personalize medicine by adapting trial populations and statistical methods. This approach, illustrated by a case example, faces implementation challenges but aids regulatory approval.
Area of Science:
- Clinical Trial Design
- Pharmacoeconomics
- Biostatistics
Background:
- Personalized medicine drives interest in adaptive enrichment for drug development.
- Various adaptive enrichment methodologies exist for exploratory and confirmatory trials.
- Adaptive enrichment aims to optimize drug development through flexible trial designs.
Purpose of the Study:
- To provide an overview of adaptive enrichment methodologies in statistical literature.
- To illustrate adaptive enrichment with a regulatory approval case example.
- To discuss challenges and design considerations for confirmatory adaptive enrichment trials.
Main Methods:
- Overview of statistical methodologies for adaptive enrichment.
- Case study analysis of a drug approval involving population and statistical information adaptation.
- Assessment of treatment effect consistency using Wang et al. (2013) approach.
Main Results:
- A case example demonstrates successful drug approval using adaptive enrichment.
- Key adaptation elements included population and statistical information adjustments.
- Challenges in implementation involve logistic aspects and adherence to pre-specified rules.
Conclusions:
- Confirmatory adaptive enrichment trials present implementation challenges.
- Consistent treatment effect estimation is crucial for regulatory reporting.
- Design considerations for adaptive enrichment include various null hypothesis frameworks.
Related Concept Videos
01:21Frequency-dependent Selection
When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
01:46Types of Selection
Natural selection influences the frequencies of particular alleles and phenotypes within populations in several different ways. Primarily, natural selection can be directional, stabilizing, or disruptive. Directional selection favors one extreme trait and shifts the population towards that phenotype while selecting against individuals displaying alternate traits. Stabilizing selection favors an intermediate trait with a narrow range of variation. Deviation from the optimal phenotype towards an...
01:28Methods of Medium Optimization
Optimizing growth media enhances microbial proliferation and maximizes product yield. Statistical experimental design methodologies provide structured and reproducible approaches, offering progressively higher levels of robustness and efficiency.The One-Factor-at-a-Time (OFAT) MethodThe One-Factor-at-a-Time (OFAT) method involves adjusting a single variable while keeping all others constant. However, it cannot detect interactions between variables, often leading to suboptimal outcomes when...
01:12Analysis of Population Pharmacokinetic Data
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
01:38Limits to Natural Selection
Organisms that are well-adapted to their environment are more likely to survive and reproduce. However, natural selection does not lead to perfectly adapted organisms. Several factors constrain natural selection.
00:57Inclusive Fitness
Most altruistic behavior—in which one animal helps another at a cost to themselves—occurs between relatives. Scientists think these altruistic behaviors evolved because they increase the inclusive fitness of the animal providing help.