An OLS-Based Method for Causal Inference in Observational Studies

Abstract

Observational data are frequently used for causal inference of treatment effects on prespecified outcomes. Several widely used causal inference methods have adopted the method of inverse propensity score weighting (IPW) to alleviate the in uence of confounding. However, the IPW-type methods, including the doubly robust methods, are prone to large variation in the estimation of causal e ects due to possible extreme weights. In this research, we developed an ordinary least-squares (OLS)-based causal inference method, which does not involve the inverse weighting of the individual propensity scores. We first considered the scenario of homogeneous treatment effect. We proposed a two-stage estimation procedure, which leads to a model-free estimator of average treatment effect (ATE). At the first stage, two summary scores, the propensity and mean scores, are estimated nonparametrically using regression splines. The targeted ATE is obtained as a plug-in estimator that has a closed form expression. Our simulation studies showed that this model-free estimator of ATE is consistent, asymptotically normal and has superior operational characteristics in comparison to the widely used IPW-type methods. We then extended our method to the scenario of heterogeneous treatment effects, by adding in an additional stage of modeling the covariate-specific treatment effect function nonparametrically while maintaining the model-free feature, and the simplicity of OLS-based estimation. The estimated covariate-specific function serves as an intermediate step in the estimation of ATE and thus can be utilized to study the treatment effect heterogeneity. We discussed ways of using advanced machine learning techniques in the proposed method to accommodate high dimensional covariates. We applied the proposed method to a case study evaluating the effect of early combination of biologic & non-biologic disease-modifying antirheumatic drugs (DMARDs) compared to step-up treatment plan in children with newly onset of juvenile idiopathic arthritis disease (JIA). The proposed method gives strong evidence of significant effect of early combination at 0:05 level. On average early aggressive use of biologic DMARDs leads to around 1:2 to 1:7 more reduction in clinical juvenile disease activity score at 6-month than the step-up plan for treating JIA.