(CR-017) Assessment of Protocol Deviations in Clinical Trials for Diabetic Foot and Venous Leg Ulcers at Tertiary Care Safety Net Hospital.

Vitaliy Volansky, DPM; Marina Malikova, PhD, MSci, MACI, MBA

Introduction: Population burden of diabetic foot (DFUs) and venous leg ulcers (VLUs) contributes to the total estimates for all Medicare spending on wounds at 37.1 billion dollars. (1) This financial burden led to increase in clinical trials to find safe, effective and cost-efficient treatments for chronic wounds. (2) Increasing number of trials contributes to operational and compliance challenges in wound healing. (3, 4) Protocol deviations are the top reason for clinical trial enforcement actions by the Food and Drug Administration (FDA). In inspections of investigative sites, approximately one-third (30%) of all warning letters are due to the failure to follow the investigational plan. (5) A risk-based approach requires a strategy to define key indicators to measure specific risks and develop mitigation plans to address non-compliance. (6)

Methods:

Analysis included 15 clinical trials with 261 participants enrolled for DFUs and VLUs indications and compared rates and types of deviations. All protocols were rated according to established complexity scoring model. (7) Statistical analyses examined associations between protocol complexity, type of study product, phase of clinical trial versus number and type of protocol deviations. Study personnel changes/experience were assessed in correlation with protocol deviations.

Results: The results of our analysis showed number of deviations (325) in VLU trials as compared to DFUs (128). VLUs and DFUs had rates of deviations of 1.9 and 1.4 per each enrolled subject, respectively. In examining association a trend was observed towards increased number of deviations once more subjects have entered the study. The highest number of deviations in both indications occurred due procedures not performed or done late. Assessment of complexity score in Pearson’s correlation test with the number of protocol deviations showed weak correlation, suggesting that other factors can influence protocol adherence. There was no correlation observed between number of deviations and type of study product utilized in the study

Discussion: Analyzing trends in protocol compliance leads to strategies to better conduct of trials. Increased deviations related to missed procedures could complicate wound healing. Different factors may effect deviations based on therapeutic indication, including co-morbidities of participants or study coordinator experience. Proactive, risk-based monitoring of protocol adherence can lead to quality improvement and mitigate issues with data integrity.

Trademarked Items:

References: 1. Chan, B., Cadarette, S., Wodchis, W., Wong, J., Mittmann, N., & Krahn, M. (2017). Cost-of-illness studies in chronic ulcers: a systematic review. Journal of wound care, 26(sup4), S4–S14. https://doi.org/10.12968/jowc.2017.26.Sup4.S4
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