Open AccessDefining and Identifying Per-protocol Effects in Randomized Trials
Author(s) -
Jacqueline E Rudolph,
Ashley I. Naimi,
Daniel Westreich,
Edward H. Kennedy,
Enrique F. Schisterman
Publication year - 2020
Publication title -
epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.901
H-Index - 173
eISSN - 1531-5487
pISSN - 1044-3983
DOI - 10.1097/ede.0000000000001234
Subject(s) - protocol (science) , counterfactual thinking , identifiability , randomized controlled trial , identification (biology) , set (abstract data type) , computer science , randomized experiment , medicine , statistics , psychology , mathematics , machine learning , surgery , social psychology , biology , pathology , alternative medicine , botany , programming language
In trials with noncompliance to assigned treatment, researchers might be interested in estimating a per-protocol effect-a comparison of two counterfactual outcomes defined by treatment assignment and (often time-varying) compliance with a well-defined treatment protocol. Here, we provide a general counterfactual definition of a per-protocol effect and discuss examples of per-protocol effects that are of either substantive or methodologic interest. In doing so, we seek to make more concrete what per-protocol effects are and highlight that one can estimate per-protocol effects that are more than just a comparison of always taking treatment in two distinct treatment arms. We then discuss one set of identifiability conditions that allow for identification of a causal per-protocol effect, highlighting some potential violations of those conditions that might arise when estimating per-protocol effects.