– Boston University, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, United States
Background: Systematic analysis of risk factors in clinical trials with cell-based combination products was performed to develop proactive benefit/risk assessment and develop mitigation strategies to improve safety and quality of trials with cardiovascular therapeutic indication. Serious adverse events (SAEs) were used as an indicator of possible safety considerations during trials with cardiovascular indication for chronic wounds conditions, and deviations were used to assess protocol adherence. Quality control in the execution phase of clinical trials is critical to producing high integrity data and helps achieve the study's objectives, particularly as biomedical research moves towards a risk based monitoring approach.
Objectives: - Monitor study protocol compliance and safety factors by tracking the rate of deviations and adverse events over time; - Determine which factors affect study efficiency; - Identify trends in deviations, adverse event occurrence and type; - Establish correlation of wound etiology with specific safety concerns.
Methods: A single center quality control (QC) audit of 36 recently completed prospective, randomized clinical trials assessed the rate of serious adverse events (SAEs) and compared two wound indications: diabetic foot ulcers (DFU) and venous leg ulcers (VLU). These studies had similar objectives, study design, eligibility criteria, and outcomes. Additionally, adherence to study protocol and compliance with current regulatory requirements was examined based on the rate of protocol deviations over time.
Results: A comparison of SAE occurrences between DFU and VLU studies showed twice as many SAEs per subject in the DFU studies as compared to the VLU studies. The most common categories were infections, both of the wound and of other anatomic locations. The onboarding of new study coordinators and multiple coordinators working independently on one trial over time consistently showed an increase in the number of deviations per active subject, particularly immediately following the date of hire. The most common categories for deviations were out-of-window visits and missed study procedures.
Conclusions: Assessment of potential issues in prospective wound care studies can lead to earlier mitigation of risks, safety and quality improvement, as well as potentially increase efficiency of studies conducted in this field. Effective training and retention of research coordinators can reduce the number of deviations, and an understanding of the frequency and types of adverse events can provide an expectation for those conducting trials in a particular indication, and assist with development of risk management strategies.
