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Andrew B. Forbes

Publications and source records attributed to Andrew B. Forbes.

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Leveraging machine learning to estimate individualized treatment effects in cluster-randomized trials

Cluster-randomized trials (CRTs) are widely used to evaluate interventions delivered at the clinic, practice, or community level. Although standard analyses typically target average treatment effects, such summaries mask potentially meaningful variation in treatment response across individuals and clusters. This work addresses the estimation of conditional average treatment effects (CATEs) for continuous outcomes in two-arm parallel CRTs by defining causal estimands that incorporate both individual- and cluster-level baseline covariates while marginalizing over unobserved cluster heterogeneity. To estimate these quantities, we develop a unified framework based on mixed-effects machine learning, integrating and extending a range of existing approaches, including Bayesian additive regression trees with random effects, multilevel Bayesian causal forests, mixed-effects random forests, several mixed-effects gradient boosting procedures, and generalized additive mixed models, while incorporating cluster-specific random intercepts to account for within-cluster dependence. We evaluate these methods across diverse simulation scenarios and demonstrate their use in the Task Shifting and Blood Pressure Control in Ghana CRT, which investigates strategies for improving hypertension management. Drawing on these investigations, we provide practical guidance for applying mixed-effects machine learning to quantify treatment-effect heterogeneity in CRTs, together with reproducible code that enables investigators to implement all methods within a coherent workflow.

stat.ME

A Bayesian approach to the survivor average causal effect in cluster-randomized crossover trials

In cluster-randomized crossover (CRXO) trials, groups of individuals are randomly assigned to two or more sequences of alternating treatments. Since clusters serve as their own control, the CRXO design is typically more statistically efficient than the usual parallel-arm design. CRXO trials are increasingly popular in many areas of health research where the number of available clusters is limited. Further, in trials among severely ill patients, researchers often want to assess the effect of treatments on secondary non-terminal outcomes, but frequently in these studies, there are patients who do not survive to have these measurements fully recorded. In this paper, we provide a causal inference framework and treatment effect estimation methods for addressing truncation by death in the setting of CRXO trials. We target the survivor average causal effect (SACE) estimand, a well-defined subgroup treatment effect obtained via principal stratification. We propose novel structural and standard modeling assumptions that enable estimating the SACE within a Bayesian paradigm. We evaluate the small-sample performance of our proposed Bayesian approach for estimation of the SACE in CRXO trial settings via simulation studies. We apply our methods to a previously conducted two-period cross-sectional CRXO study examining the impact of proton pump inhibitors compared to histamine-2 receptor blockers on length of hospitalization among adults requiring invasive mechanical ventilation.

stat.ME

What is estimated in cluster randomized crossover trials with informative sizes? -- A survey of estimands and common estimators

In the analysis of cluster randomized trials (CRTs), previous work has defined two meaningful estimands: the individual-average treatment effect (iATE) and cluster-average treatment effect (cATE) estimand, to address individual and cluster-level hypotheses. In multi-period CRT designs, such as the cluster randomized crossover (CRXO) trial, additional weighted average treatment effect estimands help fully reflect the longitudinal nature of these trial designs, namely the cluster-period-average treatment effect (cpATE) and period-average treatment effect (pATE). We define different forms of informative sizes, where the treatment effects vary according to cluster, period, and/or cluster-period sizes, which subsequently cause these estimands to differ in magnitude. Under such conditions, we demonstrate which of the unweighted, inverse cluster-period size weighted, inverse cluster size weighted, and inverse period size weighted: (i.) independence estimating equation, (ii.) fixed effects model, (iii.) exchangeable mixed effects model, and (iv.) nested exchangeable mixed effects model treatment effect estimators are consistent for the aforementioned estimands in 2-period cross-sectional CRXO designs with continuous outcomes. We report a simulation study and conclude with a reanalysis of a CRXO trial testing different treatments on hospital length of stay among patients receiving invasive mechanical ventilation. Notably, with informative sizes, the unweighted and weighted nested exchangeable mixed effects model estimators are not consistent for any meaningful estimand and can yield biased results. In contrast, the unweighted and weighted independence estimating equation, and under specific scenarios, the fixed effects model and exchangeable mixed effects model, can yield consistent and empirically unbiased estimators for meaningful estimands in 2-period CRXO trials.

stat.ME