Risk-Based Monitoring in Clinical Trials: 2021 Update.

Clinical trial quality depends on ensuring participant safety and data integrity, which require careful management throughout the trial lifecycle, from protocol development to final data analysis and submission. Recent developments-including new regulatory requirements, emerging technologies, and trial decentralization-have increased adoption of risk-based monitoring (RBM) and its parent framework, risk-based quality management (RBQM) in clinical trials. The Association of Clinical Research Organizations (ACRO), recognizing the growing importance of these approaches, initiated an ongoing RBM/RBQM landscape survey project in 2019 to track adoption of the eight functional components of RBQM. Here we present results from the third annual survey, which included data from 4889 clinical trials ongoing in 2021. At least one RBQM component was implemented in 88% of trials in the 2021 survey, compared with 77% in 2020 and 53% in 2019. The most frequently implemented components in 2021 were initial and ongoing risk assessments (80 and 78% of trials, respectively). Only 7% of RBQM trials were Phase IV, while the proportions of Phase I-III trials ranged 27-36%. Small trials (< 300 participants) accounted for 60% of those implementing RBQM. The therapeutic areas with the largest number of RBQM trials were oncology (38%), neurology (10%), and infectious diseases (9%). The 2021 survey confirmed a pattern of increasing RBM/RBQM adoption seen in earlier surveys, with risk assessments, which have broad regulatory support, driving RBQM growth; however, one area requiring further development is implementation of centralized monitoring combined with reductions in source data verification (SDV) and source data review (SDR).

Risk-Based Monitoring in Clinical Trials: Increased Adoption Throughout 2020.

With the emergence of new technologies for data collection, the continued impact of the COVID-19 pandemic, and the increasing number of partially or fully decentralized clinical trials (DCTs), the importance of risk-based monitoring (RBM) and the larger risk-based quality management (RBQM) framework in clinical trial management is increasing. RBM and RBQM focus on the detection of events or trends that impact trial quality in terms of participant safety and data integrity. In 2019, the Association of Clinical Research Organizations (ACRO) began a landscape survey of RBM/RBQM implementation in ongoing clinical trials. Initial results of this survey, representing full-year data for 2019, were reported previously. Here, we present full-year landscape data for 2020 drawn from 5,987 clinical trials ongoing at the end of 2020, including 908 new studies started that year. Of these trials, 77% implemented at least one RBM/RBQM component, an increase from 47% for studies ongoing at the end of 2019. We also observed increased implementation for three of the five RBM components included in the survey. Centralized monitoring decreased nominally in 2020 compared with 2019. Although the percentages of 2020 trials incorporating reduced source data verification (SDV) and reduced source data review (SDR) increased from 2019 to 2020, these numbers are still low considering the large percentage of trials implementing at least one RBQM component. In the current clinical trial landscape, as more DCTs are launched and new data collection technologies are implemented, there remains a pressing need for greater use of centralized monitoring coupled with reductions in SDR/SDV and, ultimately, greater adoption of RBM and RBQM.

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

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.