Variations in study outcomes relative to intention-to-treat and per-protocol data analysis techniques in the evaluation of efficacy for treatment of venous leg ulcers with dehydrated human amnion/chorion membrane allograft.

Abstract

Statistical interpretation of data collected in a randomised controlled trial (RCT) is conducted on the intention‐to‐treat (ITT) and/or the per‐protocol (PP) study populations. ITT analysis is a comparison of treatment groups including all patients as originally allocated after randomisation regardless if treatment was initiated or completed. PP analysis is a comparison of treatment groups including only those patients who completed the treatment as originally allocated, although it is often criticised because of its potential to instil bias. A previous report from an RCT conducted to evaluate the efficacy of dehydrated human amnion/chorion membrane allograft (EpiFix) as an adjunct to standard comprehensive wound therapy consisting of moist dressings and multi‐layer compression in the healing of venous leg ulcers (VLUs) only reported PP study results (n = 109, 52 EpiFix and 57 standard care patients), although there were 128 patients randomised: 64 to the EpiFix group and 64 to the standard care group. Primary study outcome was the incidence of healing at 12 weeks. The purpose of the present study is to report ITT results on all 128 randomised subjects and assess if both ITT and PP data analyses arrive at the same conclusion of the efficacy of EpiFix as a treatment for VLU. Rates of healing for the ITT and PP populations were, respectively, 50% and 60% for those receiving EpiFix and 31% and 35% for those in the standard care cohort. Within both ITT and PP analyses, these differences were statistically significant; P = 0.0473, ITT and P = 0.0128, PP. The Kaplan‐Meier plot of time to heal within 12 weeks for the ITT and PP populations demonstrated a superior wound‐healing trajectory for EpiFix compared with VLUs treated with standard care alone. These data provide clinicians and health policymakers an additional level of assurance regarding the effectiveness of EpiFix.