Risk-Based Monitoring in Clinical Trials: Past, Present, and Future

Abstract

Risk-based monitoring (RBM) is a powerful tool for efficiently ensuring patient safety and data integrity in a clinical trial, enhancing overall trial quality. To better understand the state of RBM implementation across the clinical trial industry, the Association of Clinical Research Organizations (ACRO) conducted a landscape survey among its member companies across 6,513 clinical trials ongoing at the end of 2019. Of these trials, 22% included at least 1 of the 5 RBM components: key risk indicators (KRIs), centralized monitoring, off-site/remote-site monitoring, reduced source data verification (SDV), and reduced source document review (SDR). The implementation rates for the individual RBM components ranged 8%-19%, with the most frequently implemented component being centralized monitoring and the least frequently implemented being reduced SDR. When the COVID-19 pandemic emerged in early 2020, additional data were collected to assess its impact on trial monitoring, focusing specifically on trials switching from on-site monitoring to off-site/remote-site monitoring. These mid-pandemic data show that the vast majority of monitoring visits were on-site in February 2020, but an even higher percentage were off-site in April, corresponding with the first peak of the pandemic. Despite this shift, similar numbers of non-COVID-related protocol deviations were detected from February through June, suggesting little or no reduction in monitoring effectiveness. The pre- and mid-pandemic data provide two very different snapshots of RBM implementation, but both support the need to promote adoption of this approach while also highlighting an opportunity to capitalize on the recent shift toward greater RBM uptake in a post-pandemic environment.

Fig. 1

2019 Landscape of RBM/RBQM Components in Clinical Trials. Data represent the percentage of all 6,513 trials included in the survey, not just the subset of studies that have at least one RBM component. *The KRI percentage does not include KRIs related to operations or performance.

Fig. 2

2019 Implementation of RBM/RBQM Components in Combination. Graph shows only some of the common combinations of components and not all combinations reported in the dataset.

Fig. 3

Increased Remote Monitoring Visits and RBM in Response to the COVID-19 Pandemic. Graph shows data from 1 of 3 companies providing monitoring visit data (n =  ~ 1,200 trials), but trends were similar across all 3 companies.

Fig. 4

Clinical Trial Protocol Deviations Detected by RBM During the COVID-19 Pandemic. Graph shows data from 1 of 3 companies providing protocol deviation data (n =  ~ 1,200 trials), but trends were similar across all 3 companies.