Minimizing Bias in a Diabetic Foot Ulcer Clinical Evaluation: Analysis of the HIFLO Trial

Introduction. Publications aimed at improving the quality of evidence in wound care clinical research have stressed the importance of minimizing study bias. In particular, lack of a universal definition of healing in wound studies leads to detection bias, resulting in noncomparable healing rates. Objective. This report analyzes the steps taken to reduce the main sources of bias in a particular RCT (the HIFLO Trial) that evaluated healing in DFUs using microvascular tissue. Materials and Methods. To address "definition of healing"- induced detection bias, 3 blinded adjudicators independently assessed each DFU using a rigorous 4-part definition of healing. Adjudicator responses were analyzed to assess reproducibility. Predefined criteria were also included to avoid bias owing to selection, performance, attrition, and reporting. Results. Rigor and comparability across sites were ensured through investigator training, consistent SOC, data monitoring, and independent statistical and ITT-only analysis. The level of agreement among adjudicators was greater than or equal to 90% for each of the 4-part healing criteria. Conclusions. High-level agreement by blinded adjudicators confirmed that DFUs in the HIFLO Trial were consistently assessed for healing without bias, validating the most rigorous assessment criteria to date. The findings reported herein may prove beneficial for others seeking to minimize bias in wound studies.