Comparing per-protocol effect estimates for population health RCTs: A re-analysis of the Feeding America intervention trial for health for diabetes mellitus

Intent-to-treat (ITT) effects are typically the parameter of interest in randomized clinical trials (RCTs). But ITT estimates have drawbacks, particularly when adherence is low. Thus, complementing estimates of ITT effects with estimates of per-protocol effects—the effect of receiving the assigned protocol through the duration of the study—is often useful.

For example, the ITT estimate from the Feeding America Intervention Trial for Health—Diabetes Mellitus (FAITH-DM) did not find that the intervention reduced hemoglobin A1c (HbA1c) at 6 months (difference in HbA1c between intervention and comparison group = 0.24%; 95% confidence interval (CI): –0.09, 0.58). However, as with many interventions meant for low-income populations, the same conditions that prompted intervention made adherence difficult. Thus, presenting only ITT estimates does not address whether the intervention works as intended when adhered to, or whether refinements to overcome additional barriers may be useful. Estimates of per-protocol effects can help answer this question. Here, we provide an example of estimating time-fixed per-protocol effects and compare several different estimators, including doubly robust estimators, which have seldom been used in this setting.