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.

Placental-Derived Biomaterials and Their Application to Wound Healing: A Review

“…The research consistently demonstrates the effectiveness of placental-derived biomaterials to treat diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). Several of these high-level studies compared the application of placental-derived biomaterials with standard wound care and demonstrated that the application of placental-derived biomaterials significantly improves the proportion of healed ulcers [132,135,137,171,175,181,[184][185][186][187]189,190], time to healing and rates of healing [132,135,137,175,[184][185][186][187]191], and ulcer size [171,180,182,189,191]. In addition, Selena and colleagues [190] reported that 79.5% of patients treated with dHACM and multilayer compression therapy reported reduced VLU pain, compared with 52.4% patients who were treated with multilayer compression therapy alone.…”

Principais evidências clínicas acerca dos tratamentos tópicos atuais para úlcera venosa de perna: uma revisão sistemática

“…Destaca-se que avanços recentes na biotecnologia resultaram no desenvolvimento de vários biomateriais para o tratamento de feridas, incluindo bioengenharia de pele cultivada a partir de células de doadores humanos (aloenxertos), como identificada nos estudos de Bianchi et al (2018) e Bianchi et al (2019).…”

Potential cost‐effectiveness of using adjunctive dehydrated human amnion/chorion membrane allograft in the management of non‐healing diabetic foot ulcers in the United Kingdom

“…Hence, the relative cost‐effectiveness of using dHACM outside of secondary care is unknown at this time and it is not possible to predict with any certainty what its cost‐effectiveness might be in primary care. Because the economic analysis was based on the results of a single RCT in non‐healing DFUs, it precludes generalisation of our findings to patients with other wound types, although adjunctive dHACM has been shown to be efficacious in treating non‐healing venous leg ulcers 23 , 24 and difficult‐to‐heal fistulas. 25 Predicting whether the use of dHACM would be cost‐effective in treating these wound types is beyond the remit of this study because the patient pathways and treatment algorithms for non‐healing venous leg ulcers and difficult‐to‐heal fistulas differ from those of non‐healing DFUs.…”