Estimation of causal effects of multiple treatments in healthcare database studies with rare outcomes

TL;DR

This study compares different causal inference methods for estimating treatment effects in healthcare databases with rare outcomes and multiple treatments, highlighting BART and RAMS as more accurate than IPTW.

Contribution

It introduces and evaluates three causal analysis strategies tailored for healthcare data with multiple treatments and rare outcomes, filling a gap in existing literature.

Findings

BART and RAMS show lower bias and mean squared error.

IPTW methods have less favorable operating characteristics.

The methods are demonstrated in a case study on lung cancer treatments.

Abstract

The preponderance of large-scale healthcare databases provide abundant opportunities for comparative effectiveness research. Evidence necessary to making informed treatment decisions often relies on comparing effectiveness of multiple treatment options on outcomes of interest observed in a small number of individuals. Causal inference with multiple treatments and rare outcomes is a subject that has been treated sparingly in the literature. This paper designs three sets of simulations, representative of the structure of our healthcare database study, and propose causal analysis strategies for such settings. We investigate and compare the operating characteristics of three types of methods and their variants: Bayesian Additive Regression Trees (BART), regression adjustment on multivariate spline of generalized propensity scores (RAMS) and inverse probability of treatment weighting (IPTW) with multinomial logistic regression or generalized boosted models. Our results suggest that BART and RAMS provide lower bias and mean squared error, and the widely used IPTW methods deliver unfavorable operating characteristics. We illustrate the methods using a case study evaluating the comparative effectiveness of robotic-assisted surgery, video-assisted thoracoscopic surgery and open thoracotomy for treating non-small cell lung cancer.