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.

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

“…As previously reported, an independent outside vendor collected, blinded, aggregated, and analyzed the data [ 3 ]. The original dataset captured trials that were ongoing as of December 31, 2019, including studies initiated in 2019 and multi-year studies initiated in years prior.…”

“…This more efficient approach to trial monitoring is an integral part of the risk-based quality management (RBQM) framework, described by the European Medicines Agency (EMA) in 2013 as “a systematic process put in place to identify, assess, control, communicate and review the risks associated with the clinical trial during its lifecycle.” [ 1 ]. Despite a growing body of evidence showing the benefits of RBM in clinical trial management, adoption has been slow and implementation incomplete [ 2 , 3 ]. The COVID-19 pandemic, however, has highlighted the benefits of implementing RBM alone and as part of a broader RBQM approach.…”

“…ACRO’s mission is to advocate to regulators and policymakers on behalf of the clinical research industry, educate stakeholders, and help inform policy. We previously reported results from ACRO’s landscape survey on the implementation of RBM/RBQM components across 6513 clinical trials ongoing at the end of 2019, as well as additional data on trial execution during the first half of 2020, at the onset of the COVID-19 global pandemic [ 3 ].…”

“…Among the most significant findings of the landscape survey was that prior to the pandemic, only 22% of trials included at least one RBM component, with each individual component being implemented in just 8–19% of trials [ 3 ]. There was, however, a rapid shift from 82% trials using on-site monitoring in February 2020 to 93% of trials using remote monitoring in April 2020, corresponding with the first wave of the pandemic.…”

Feasibility and acceptability of a structured quality by design approach to enhancing the rigor of clinical studies at an academic health center

“…Over the past few decades, there have been various efforts aimed at creating and disseminating innovative approaches that help embed quality metrics into the design, conduct, and monitoring of clinical trials. These efforts have been led by key stakeholders in the global clinical trial enterprise, including international regulatory agencies (such as the Food and Drug Administration [FDA] and International Council for Harmonization [ICH]), the pharmaceutical and medical device industries, National Institute of Health (NIH), and academic institutions [9][10][11][12]. One such effort which has gained traction in the last few years leverages and adapts Quality by Design (QbD) concepts frequently used in the manufacturing sectors (i.e., automotive and pharmaceutical manufacturing) for the purpose of clinical research.…”