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

Background: Statistical interpretation of data collected in a randomized 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 randomization regardless if treatment was initiated or completed. Per-protocol analysis is a comparison of treatment groups including only those patients who completed the treatment as originally allocated, though is often criticized due to its potential to instill bias. A previous report from an RCT conducted to evaluate the efficacy of dehydrated human amnion/chorion membrane allograft (dHACM) 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 dHACM, and 57 standard care patients), although there were 128 patients randomized: 64 to the dHACM group and 64 to the standard care group. Primary study outcome was the incidence of healing at 12 weeks.

Purpose: The purpose of the present study is to report ITT results on all 128 randomized subjects and assess if both ITT and PP data analysis arrive at the same conclusion of efficacy for dHACM as a treatment for VLU.

Results: Rates of healing for the ITT and PP populations were 50% and 60% for those receiving dHACM and 31% and 35% respectively 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. Kaplan-Meier plot of time-to-heal within 12 weeks for the ITT and PP populations, demonstrated a superior wound healing trajectory for dHACM compared to VLUs treated with standard care alone.

Conclusion: These data provide clinicians and health policy makers an additional level of assurance regarding the effectiveness of dHACM.