The U.S. Food and Drug Administration opened the door to a new era of clinical trial management last summer when it released guidance for industry on clinical trial oversight and called for expanded use of risk-based monitoring. Specifically, it encouraged sponsors to take advantage of electronic systems and focus clinical trial oversight activity on preventing risks to data quality and critical processes to patient safety and trial integrity.
Risk-based monitoring represents a smarter way to monitor clinical trials - a holistic, dynamic approach focusing on risk factors with the intent to conduct clinical trials more efficiently and cost-effectively, while ensuring patient safety, data integrity and compliance.
Industry best practices have long dictated that monitors visit each investigator site regularly to evaluate data and processes that impact patient safety and protocol compliance, and to conduct 100% source data verification (SDV). Risk-based monitoring turns that around through a focus on centralized and off-site monitoring instead of full on-site monitoring, and an emphasis on partial (or targeted) source data verification.
With risk-based monitoring, the role of the monitor doesn’t change – just as the reasons we monitor haven’t changed. However, technology will play an expanded role in helping clinical research associates (CRAs) execute risk-based monitoring strategies.
Core clinical systems should include activity-based study modeling, true end-to-end clinical data management, clinical trial management system, safety monitoring systems and operational analytics to inform study design and tie systems together in a single source of truth. In addition, innovative mobile apps are emerging that provide CRAs with visibility into real-time trial and site operational data that help them determine, based on critical data and process indicators such as screen failure rates, if they can skip a planned visit or make an unplanned visit – all while on the road. CRAs can leverage this increased mobility to help them manage the on-site visits they do make to be more efficient and productive, and adapt more quickly to changes.
Due to overarching concerns about patient safety, trial managers have been apprehensive to become early adopters of risk-based monitoring – despite the evident cost and efficiency benefits. Now, with guidance from the FDA, European Medicines Agency (EMA), and Medicines and Healthcare Products Regulatory Agency (MHRA), as well as a widespread industry-group support and tools, such as TransCelerate’s Risk Assessment Categorization Tool, sponsors and contract research organizations (CROs) are starting to actively implement risk-based monitoring.
Successful risk-based monitoring really comes down to three factors - the upfront risk assessment identifying the critical data and processes for that study; quality design and consistent application of that risk assessment across the organization (e.g., people, partners, processes, and investigator sites) and trial workflow (e.g., clinical systems, protocol design, and trial design); and the ability to quickly and easily track the critical data and processes identified in the risk assessment.
The benefits of risk-based monitoring are compelling. By reducing SDV – the most time-consuming activity for monitors on-site – CRAs can focus on more critical compliance activities, like patient-informed consent, completion of essential documents and site compliance with study protocol and Good Clinical Practice (GCP) principles. In addition, other studies suggest that data anomalies such as non-random data distributions and fabrication of data may be more easily detected by centralized monitoring versus frequent on-site monitoring. With regulatory guidance, industry standards and tools, and advances in technology, the path is clearer for adoption of effective risk-based monitoring to reduce trial time, cost and risk. Most importantly of all, however, the increased adoption of risk-based monitoring will help enhance patient safety.