Emulation of Target Trials to Study the Effectiveness and Safety of Medical Interventions

Abstract

Ideally, clinical guidelines would be informed by well-designed randomized experiments. However, it is generally not possible to conduct a randomized trial for every clinically relevant decision. Decision makers therefore often have to rely on observational data. Guidelines that rely on observational data due to the absence of randomized trials benefit when the analysis mimics the analysis of a hypothetical target trial. This can be achieved by explicitly formulating the protocol of the target trial, and thoroughly discussing the feasibility of the conditions that must be met in order to validly emulate the target trial using observational data.

In chapter one, we discuss the emulation of trials that compare the effects of different timing strategies, that is, strategies that vary the frequency of delivery of a medical intervention or procedures, and provide an application to surveillance for colorectal cancer. In chapter two, we discuss a study design that attempts to avoid bias by comparing initiators of the treatment of interest with initiators of an “active comparator” that is believed to be inactive for the outcome, in order to emulate a randomized trial that compares the treatment of interest with an inactive comparator. In chapter three, we describe a new method that combines randomized trial data and external information to emulate a different target trial. We apply this method to a randomized trial of postmenopausal hormone therapy in order to emulate a trial of a joint intervention on hormone therapy and statin therapy.