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

Brian Barnes,Debra Jendrasek,Andrea Mcsweeney,Anina Adelfio,Nickolas Piccoli,Geoff Gerard,Nycole Ramirez,Vanesa Castillo,Ruth Berlien,Nick May,Lauren Garson,Paula Jo Butler,Nicole Stansbury,Debby Brown

doi:10.1007/s43441-021-00295-8

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.

Highlights

Clinical trial management is a complex endeavor requiring careful planning, compliance with regulations, and coordination between multiple stakeholders such as sponsors, investigators, and contract research organizations (CROs)
Risk-based monitoring (RBM) is an important component of a larger framework known as risk-based quality management (RBQM), defined in a 2013 European Medicines Agency (EMA) reflection paper as “a systematic process put in place to identify, assess, control, communicate and review the risks associated with the clinical trial during its lifecycle” [1–3]
Compared with source data verification (SDV), source document review (SDR), and other forms of monitoring focused on past events, RBM has a stronger focus on the present and future, when it includes real-time monitoring and predictive modeling [4]

Summary

Introduction

Clinical trial management is a complex endeavor requiring careful planning, compliance with regulations, and coordination between multiple stakeholders such as sponsors, investigators, and contract research organizations (CROs). The aim of RBM is to focus monitoring on those trial processes most likely to affect patient safety and data quality, often using real-time analytics, so that investigators can more quickly and effectively mitigate risks or address errors before they compromise trial quality. Compared with source data verification (SDV), source document review (SDR), and other forms of monitoring focused on past events, RBM has a stronger focus on the present and future, when it includes real-time monitoring and predictive modeling [4]. These forwardlooking activities impact monitoring functions and overall trial management. RBQM directly addresses the directives on RBM contained in the ICH E6(R2) guidance [5]

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Discussion

Conclusion