Supervised variable selection in randomised controlled trials prior to exploration of treatment effect heterogeneity: an example from severe malaria

Chieh-Hsi Wu; Chris C. Holmes

Home/Archive/arXiv

arXiv · 1901.03531

Supervised variable selection in randomised controlled trials prior to exploration of treatment effect heterogeneity: an example from severe malaria

Chieh-Hsi Wu·Chris C. Holmes

View original source ↗Read source document ↗Export metadata ↓

Abstract

Exploration of treatment effect heterogeneity (TEH) is an increasingly important aspect of modern statistical analysis for stratified medicine in randomised controlled trials (RCTs) as we start to gather more information on trial participants and wish to maximise the opportunities for learning from data. However, the analyst should refrain from including a large number of variables in a treatment interaction discovery stage. Because doing so can significantly dilute the power to detect any true outcome-predictive interactions between treatments and covariates. Current guidance is limited and mainly relies on the use of unsupervised learning methods, such as hierarchical clustering or principal components analysis, to reduce the dimension of the variable space prior to interaction tests. In this article we show that outcome-driven dimension reduction, i.e. supervised variable selection, can maintain power without inflating the type-I error or false-positive rate. We provide theoretical and applied results to support our approach. The applied results are obtained from illustrating our framework on the dataset from an RCT in severe malaria. We also pay particular attention to the internal risk model approach for TEH discovery, which we show is a particular case of our method and we point to improvements over current implementation.

Explore related subjects

stat.ME stat.AP

Keep this discovery

BibTeX RIS

Chieh-Hsi Wu, Chris C. Holmes. 2019-01-11. Supervised variable selection in randomised controlled trials prior to exploration of treatment effect heterogeneity: an example from severe malaria. https://arxiv.org/abs/1901.03531

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Surprise Reduction and Nullification in Bayesian and Inverse Bayesian Inference under Ambiguous Prediction-Error Attribution

In non-stationary environments, prediction errors may signal environmental change or transient outliers, and adaptive systems must track such changes without overreacting to outliers. We distinguish surprise reduction, which updates beliefs to fit observations, from surprise nullification, which weakens constraints imposed by the predictive structure, and formalize both within Bayesian and inverse Bayesian (BIB) inference. Belief and likelihood updates are derived from variational objectives sharing a nullification strength, determined endogenously by minimizing surprise under the candidate post-update predictive distribution. In the Gaussian case, nullification expands belief and likelihood variances by a common factor relative to standard Bayesian updating, leaving the ratio unchanged. BIB thus defers attribution of the prediction error, committing to neither latent-state change nor observation-process uncertainty. The nullification strength is carried over as a candidate and is maintained or released according to the predictive surprise of the next observation. In a mean estimation task with outliers and changepoints, no scanned parameter setting of a Sage-Husa-type adaptive Kalman filter, fixed-strength BIB variant, or belief-forgetting-only variant outperforms BIB in both changepoint tracking and post-outlier stability. An oracle-informed reduced Bayesian model tracks changepoints better but is less stable after outliers. Although BIB maintains no explicit hypotheses about changepoints or outliers, it generates event-dependent dynamics. The learning rate increases after changepoints, whereas after outliers, nullification is released, and this increase is suppressed. Deferring attribution and letting subsequent observations differentiate the responses may constitute a principle of adaptive inference in non-stationary environments.

stat.ME↗

arXiv2026

Generalized Ridge Refitting for the Lasso and Prediction Improvement Bounds

We study a class of Lasso based estimators obtained by applying a quadratic correction on the Lasso equicorrelation set. The penalty matrix determines both the magnitude and geometry of the correction and contains, among other cases, the isotropic Lasso--Ridge correction, least squares refitting, Gram proportional interpolation between the Lasso and least squares, and coordinate specific penalties. We first derive a closed form representation and isolate the positive gain component of the resulting prediction improvement. We then control the remaining stochastic linear term in expectation by localizing the random signed equicorrelation model around a deterministic reference support. This yields a finite sample expectation bound that explicitly accounts for the randomness induced by Lasso model selection. The resulting decomposition provides a unified framework for understanding when Lasso based quadratic corrections can improve prediction.

stat.ME↗

arXiv2026

Discretization in covariate-adaptive randomization: gains and losses

Covariate-adaptive randomization(CAR) is widely implemented in clinical trials to balance prognostic covariates across treatment arms. Continuous covariates are often discretized into strata in practice, yet their consequences are not clearly understood. This paper provides a comprehensive study of the impact of discretization on both the CAR design process and the inferential results thereafter. We establish the asymptotic properties of both imbalance measures and treatment effect estimators under discretized and non-discretized settings. Practical recommendations are given on when and how discretization should be employed. We show that discretization in design is generally recommended, as it enhances robustness against model misspecification. However, if the true model is known, the most efficient strategy is to balance covariates according to that model in the design. The theoretical results are corroborated by extensive simulation studies and an empirical application to a diabetes trial dataset. Together, the results clarify the gains and losses of discretization in CAR and pave the way for learning impact of discretization to other designs and beyond.

stat.ME↗