Observational data for comparative effectiveness research: An emulation of randomised trials of statins and primary prevention of coronary heart disease

TLDR

This article reviews methods for comparative effectiveness research using observational data to emulate randomized trials. The authors emulate a randomized trial by comparing statin initiators to non‑initiators, adjusting for baseline and time‑varying confounders with inverse‑probability weighting, and apply this framework to UK electronic medical record data, providing an annotated SAS program. The emulated analyses detected a potential benefit of statins, with intention‑to‑treat, per‑protocol, and as‑treated hazard ratios of 0.89, 0.84, and 0.79 respectively, whereas a conventional comparison of current versus never users yielded a higher hazard ratio of 1.31.

Abstract

This article reviews methods for comparative effectiveness research using observational data. The basic idea is using an observational study to emulate a hypothetical randomised trial by comparing initiators versus non-initiators of treatment. After adjustment for measured baseline confounders, one can then conduct the observational analogue of an intention-to-treat analysis. We also explain two approaches to conduct the analogues of per-protocol and as-treated analyses after further adjusting for measured time-varying confounding and selection bias using inverse-probability weighting. As an example, we implemented these methods to estimate the effect of statins for primary prevention of coronary heart disease (CHD) using data from electronic medical records in the UK. Despite strong confounding by indication, our approach detected a potential benefit of statin therapy. The analogue of the intention-to-treat hazard ratio (HR) of CHD was 0.89 (0.73, 1.09) for statin initiators versus non-initiators. The HR of CHD was 0.84 (0.54, 1.30) in the per-protocol analysis and 0.79 (0.41, 1.41) in the as-treated analysis for 2 years of use versus no use. In contrast, a conventional comparison of current users versus never users of statin therapy resulted in a HR of 1.31 (1.04, 1.66). We provide a flexible and annotated SAS program to implement the proposed analyses.