Since the FDA and EMA released guidance on risk-based monitoring in 2013, implementation of the laid-out principles has matured into a risk-based quality management (RBQM) approach. RBQM is a more holistic approach to trial management when compared to risk-based monitoring, including robust risk assessment from the start of the trial, continued risk management and central monitoring throughout the trial, as well as comprehensive oversight of quality metrics.
This article details some of the findings from our white paper exploring the best practices for developing a comprehensive quality management approach that supports RBQM methodologies, and reports practical quality measures used to evaluate the overall benefit and impact of such an approach.
Upon release of the regulatory guidance in 2013, Covance created the operational processes and implemented Xcellerate® technology for risk-based monitoring. Following the positive results of this initial pilot phase, Covance transformed this risk-based monitoring approach into a comprehensive, end-to-end RBQM solution. As more studies have implemented Xcellerate, more measurable proof was sought to quantify the efficiency and quality benefits generated by RBQM.
Assessing the benefits and impact
The metrics we report in this study work well to compare studies executed with and without the RBQM approach. In addition to quality metrics, we have identified a number of efficiency metrics that should be positively impacted by RBQM.
Effective and proactive central risk monitoring should reduce time needed for on-site monitoring. Effective tools for central data review should reduce physician's time, enhance medical issue detection, and improve patient retention during the trial. A robust solution for risk and issue management should accelerate issue resolution and decrease issue aging. Further, the overall data quality oversight should enhance accuracy and timelines of data collection, hopefully resulting in a faster database lock.
The Covance team began evaluating efficiency metrics by considering the impact of Xcellerate® Risk Review in assessing the reduction in time spent on-site monitoring. Considering 129 studies that took place over the past five years with at least 500 monitoring hours recorded, a 38% reduction was observed in time spent on-site monitoring with mega-trials and 34% without mega-trials.
With such a substantial reduction in time discovered, the study team considered time spent on-site in activities outside of site monitoring. A small reduction of 7% in site management was observed, verifying that the 38% reduction in site monitoring time is not significantly offset by other activities.
Considered together with the reduction in the time spent on-site monitoring, the observed reduction in the overall site management time is significant and important for the industry. Sponsors that embrace RBQM will utilize site management resources more efficiently which should promote increased study quality through the benefit of additional efficiencies.
Evaluating quality metrics
To assess the impact of RBQM on study quality, we considered a reduction in critical and major findings from the site oversight quality control (QC) visits. Utilizing the RBQM approach, we observed a 46% reduction with mega-trials and a 44% reduction without mega-trials. For major findings, the reduction was 28% and 25%, respectively.
In order to determine the efficiency of the medical review process, we examined early terminations normalized to the enrolled subjects. A significant reduction of 67% in early terminations was noted when medical review processes were applied. Even when normalizing early terminations to subject exposure to account for longer studies, a 46% reduction in early terminations was found.
Additionally, we found a reduction of 28% in important protocol deviations when the RBQM approach was implemented.
Understanding the challenges and looking ahead
Our metrics have shown that RBQM methodologies increase the quality and efficiency of study delivery in the ways that were anticipated. Still, there are more areas to assess, including comparisons across therapeutic areas and the impact on time from the last patient visit to database lock.
Using our experience at Covance as a guide, we report that RBQM implementation is a challenging and iterative process. We encourage study sponsors and other CROs to collaborate and share their approach to measuring success and impact. Together, we hope to establish industry benchmarks to help others on their RBQM journey.