Minimizing bias in massive multi-arm observational studies with BCAUS: balancing covariates automatically using supervision

Abstract

Background: Observational studies are increasingly being used to provide supplementary evidence in addition to Randomized Control Trials (RCTs) because they provide a scale and diversity of participants and outcomes that would be infeasible in an RCT. Additionally, they more closely reflect the settings in which the studied interventions will be applied in the future. Well-established propensity-score-based methods exist to overcome the challenges of working with observational data to estimate causal effects. These methods also provide quality assurance diagnostics to evaluate the degree to which bias has been removed and the estimates can be trusted. In large medical datasets it is common to find the same underlying health condition being treated with a variety of distinct drugs or drug combinations. Conventional methods require a manual iterative workflow, making them scale poorly to studies with many intervention arms. In such situations, automated causal inference methods that are compatible with traditional propensity-score-based workflows are highly desirable. Methods: We introduce an automated causal inference method BCAUS, that features a deep-neural-network-based propensity model that is trained with a loss which penalizes both the incorrect prediction of the assigned treatment as well as the degree of imbalance between the inverse probability weighted covariates. The network is trained end-to-end by dynamically adjusting the loss term for each training batch such that the relative contributions from the two loss components are held fixed. Trained BCAUS models can be used in conjunction with traditional propensity-score-based methods to estimate causal treatment effects. Results: We tested BCAUS on the semi-synthetic Infant Health & Development Program dataset with a single intervention arm, and a real-world observational study of diabetes interventions with over 100,000 individuals spread across more than a hundred intervention arms. When compared against other recently proposed automated causal inference methods, BCAUS had competitive accuracy for estimating synthetic treatment effects and provided highly concordant estimates on the real-world dataset but was an order-of-magnitude faster. Conclusions: BCAUS is directly compatible with trusted protocols to estimate treatment effects and diagnose the quality of those estimates, while making the established approaches automatically scalable to an arbitrary number of simultaneous intervention arms without any need for manual iteration.