Guidelines for estimating causal effects in pragmatic randomized trials


Murray EJ, Swanson SS, Hernan MA. Guidelines for estimating causal effects in pragmatic randomized trials. arXiv preprint arXiv:1911.06030. Working Paper.


Pragmatic randomized trials are designed to provide evidence for clinical decision-making rather than regulatory approval. Common features of these trials include the inclusion of heterogeneous or diverse patient populations in a wide range of care settings, the use of active treatment strategies as comparators, unblinded treatment assignment, and the study of long-term, clinically relevant outcomes. These features can greatly increase the usefulness of the trial results for patients, clinicians, and other stakeholders. However, these features also introduce an increased risk of non-adherence, which reduces the value of the intention-to-treat effect as a patient-centered measure of causal effect. In these settings, the per-protocol effect provides useful complementary information for decision making. Unfortunately, there is little guidance for valid estimation of the per-protocol effect. Here, we present our full guidelines for analyses of pragmatic trials that will result in more informative causal inferences for both the intention-to-treat effect and the per-protocol effect.

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