Instrumental Variable Approach to Estimating Individual Causal Effects in N-of-1 Trials: Application to ISTOP Study

TL;DR

This paper introduces a Bayesian instrumental variable approach for estimating individual causal effects in N-of-1 trials, effectively addressing challenges like non-compliance, binary data, and serial correlation, demonstrated through simulations and application to AF study.

Contribution

It develops a novel Bayesian IV framework for personalized causal inference in N-of-1 trials, overcoming key methodological challenges and improving estimation accuracy.

Findings

Reduced bias in causal effect estimates compared to existing methods

Improved coverage probabilities in simulation studies

Successfully applied to real AF data to assess alcohol's impact

Abstract

An N-of-1 trial is a multiple crossover trial conducted in a single individual to provide evidence to directly inform personalized treatment decisions. Advancements in wearable devices greatly improved the feasibility of adopting these trials to identify optimal individual treatment plans, particularly when treatments differ among individuals and responses are highly heterogeneous. Our work was motivated by the I-STOP-AFib Study, which examined the impact of different triggers on atrial fibrillation (AF) occurrence. We described a causal framework for 'N-of-1' trial using potential treatment selection paths and potential outcome paths. Two estimands of individual causal effect were defined:(a) the effect of continuous exposure, and (b) the effect of an individual observed behavior. We addressed three challenges: (a) imperfect compliance to the randomized treatment assignment; (b) binary treatments and binary outcomes which led to the 'non-collapsibility' issue of estimating odds ratios; and (c) serial inference in the longitudinal observations. We adopted the Bayesian IV approach where the study randomization was the IV as it impacted the choice of exposure of a subject but not directly the outcome. Estimations were through a system of two parametric Bayesian models to estimate the individual causal effect. Our model got around the non-collapsibility and non-consistency by modeling the confounding mechanism through latent structural models and by inferring with Bayesian posterior of functionals. Autocorrelation present in the repeated measurements was also accounted for. The simulation study showed our method largely reduced bias and greatly improved the coverage of the estimated causal effect, compared to existing methods (ITT, PP, and AT). We applied the method to I-STOP-AFib Study to estimate the individual effect of alcohol on AF occurrence.