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result(s) for
"Heterogeneity of treatment effect (HTE)"
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Who benefits? Uncovering hidden heterogeneity of treatment effects in adaptive trials using Bayesian methods: a systematic review
by
Giblon, Rachel
,
Liu, Kuan
,
Goligher, Ewan C.
in
Adaptation
,
Adaptive clinical trials
,
Adaptive Clinical Trials as Topic - methods
2025
Background
Adaptive clinical trials increasingly aim to detect heterogeneity of treatment effect (HTE) to guide personalized care. However, most adaptive designs rely on predefined subgroups and are limited in their ability to uncover unknown or complex sources of HTE. Bayesian statistical methods offer a flexible alternative, enabling real-time learning and adaptation within trials. This review evaluates Bayesian methods used to detect hidden HTE in adaptive clinical trials, with attention to their methodological innovations, operating characteristics, and consideration of equity and inclusion in trial design.
Methods
We conducted a systematic search of MEDLINE, Embase, and other databases to identify original studies that developed Bayesian methods for detecting unknown HTE within adaptive clinical trial designs. Eligible studies were reviewed and synthesized based on design features, statistical methodology, operating characteristics, reproducibility, and whether equity-related factors were explicitly considered. Equity considerations included whether studies incorporated variables related to underrepresented populations—such as age, sex, race/ethnicity, or geography—examined intersectional subgroup effects, or explicitly framed their methods as tools to address health disparities.
Results
Of 2826 screened records, seven studies met inclusion criteria. Bayesian methods included random partition models, spatial models, logistic regression with dimension reduction, adaptive randomization using machine learning classifiers, and adaptive enrichment or platform designs incorporating model averaging or latent subgroup estimation. In simulation studies, these methods often showed improvements in subgroup detection, efficiency, or power relative to non-Bayesian comparators. None were tested using real-world trial data. Reproducibility was limited overall, with analytic code only available for the three most recent studies. Notably, none explicitly framed their methods as tools to address inequities in treatment outcomes across population subgroups.
Conclusions
The small number of simulation-based studies illustrates preliminary but promising directions for applying Bayesian methods to detect HTE in adaptive clinical trials. While these approaches demonstrate potential to enhance trial adaptability, scalability, and inclusiveness, current evidence remains limited and largely conceptual. Incorporating an equity lens into future methodological development, alongside greater emphasis on empirical validation and open science practices, will be essential to determine their practical value in advancing equitable clinical research.
Journal Article
Evaluating the heterogeneous effect of a modifiable risk factor on suicide: The case of vitamin D deficiency
by
Petukhova, Maria V.
,
Streeten, Elizabeth A.
,
Tizenberg, Boris
in
Case-Control Studies
,
causal forest algorithm
,
heterogeneity of treatment effects (HTE)
2022
Objectives To illustrate the use of machine learning methods to search for heterogeneous effects of a target modifiable risk factor on suicide in observational studies. The illustration focuses on secondary analysis of a matched case‐control study of vitamin D deficiency predicting subsequent suicide. Methods We describe a variety of machine learning methods to search for prescriptive predictors; that is, predictors of significant variation in the association between a target risk factor and subsequent suicide. In each case, the purpose is to evaluate the potential value of selective intervention on the target risk factor to prevent the outcome based on the provisional assumption that the target risk factor is causal. The approaches illustrated include risk modeling based on the super learner ensemble machine learning method, Least Absolute Shrinkage and Selection Operator (Lasso) penalized regression, and the causal forest algorithm. Results The logic of estimating heterogeneous intervention effects is exposited along with the illustration of some widely used methods for implementing this logic. Conclusions In addition to describing best practices in using the machine learning methods considered here, we close with a discussion of broader design and analysis issues in planning an observational study to investigate heterogeneous effects of a modifiable risk factor.
Journal Article