Emulating a Randomised Controlled Trial With Observational Data: An Introduction to the Target Trial Framework

Abstract

Randomised controlled trials (RCTs) are often considered to be the highest quality of evidence owing to the absence of baseline confounding, the simplicity of analyses, and direct estimation of causal effects. However, observational studies can be designed to mimic RCTs and estimate causal treatment effects. In this review, we describe the target trial framework to illustrate how observational studies can successfully emulate RCTs. We focus on key design elements of RCTs and how to emulate them with observational data. These elements include 1) eligibility criteria, 2) treatment assignment and randomisation, 3) specification of "time zero", 4) outcomes, 5) follow-up, 6) causal contrasts (intention-to-treat vs per-protocol), and 7) statistical analyses. In addition, we describe the design of an example target trial created to emulate the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial and compare effect estimates. Overall, careful design of a target trial using observational data can produce causal effect estimates that are often comparable to RCTs.