The monitoring of clinical trials is essential to ensure that human research is conducted safely, accurately, and effectively. The costs and complexity associated with these studies continue to rise rapidly, so it is critical for industry to explore developing methodologies and technologies for monitoring approaches aimed at increasing efficiencies and reducing expenses. Combining on-site and remote monitoring into a dynamic plan known as Risk-based Monitoring (RBM) is emerging.
Historically, monitoring has consisted of frequent periodic site visits with 100% source data verification. Recent advances in technology have allowed for remote, or centralized, monitoring to be utilized as well. Benefits include routine review of data in real-time for earlier identification and assessment of consistency and completeness of data; unusual data distribution; and higher risk sites for more frequent or more intensive on-site monitoring.
RBM has gained in popularity in recent years, and FDA’s 2013 Guidance for Industry titled “Oversight of Clinical Investigations – a Risk-Based Approach to Monitoring” has encouraged its use. FDA recommends considering all the potential sources of risk for the study at each trial site, focusing on critical study parameters, and then planning a combination of monitoring activities to oversee the study effectively.
Decreasing the frequency of on-site visits should not result in a lower standard of monitoring. Rather, utilizing the tools for risk assessment will increase the quality of oversight efforts as the advantages of remote monitoring for ongoing detection of data errors can be realized, and on-site visits can be more effectively deployed.
RBM plans are created by first identifying the Key Risk Indicators (KRIs) for the particular trial. These are factors, parameters, metrics, and critical data points that are sources of risk of deviations or failures in study conduct or progress. Examples include: complexity of the trial protocol; potential for unanticipated adverse device effects; complexity of shipping logistics; and level of technical difficulty of the investigational device. Once KRIs are identified, they are assigned a risk level of high, medium, or low. A trial monitoring plan and schedule can then be prepared focusing more robustly on mitigation of the higher-ranking KRIs. Throughout the trial, risk levels may change and analysis of performance may reveal unexpected trending. These conditions may force the need to modify the monitoring plan.
Quality, cost-effectiveness, conservation of monitoring resources, and 100% protocol compliance can be maintained using RBM. Many have reported their successes. In the scenario of a multi-national, multi-site trial where subject data were collected through direct data entry at the time of the office visit, review of data in real-time helped to:
- identify appropriate remote and on-site monitoring follow-up tasks;
- identify needed protocol amendments quickly for early implementation during the trial;
- expedite data corrections by use of electronic edit and logic checks
- decrease queries; and
- facilitate timely updated training for monitors and site staff.
As the paradigm moves away from 100% source data verification, clinical trial monitors should develop the skills needed to best leverage RBM technologies. Quickly mastering the basics as well as some of the intricacies of risk assessment, electronic data capture, and electronic investigator site files will allow the monitor to ensure that data are properly stored and shared among stakeholders. Then, monitors must have the ability to interpret and assess large amounts of incoming data; address any emerging KRIs; and confirm that the trial is being properly conducted.
Reforms to the clinical trials process are vital to ensure that future studies can be conducted more efficiently while still ensuring protection of trial subject rights and safety and maintaining data integrity. Risk-based monitoring is an effective methodology proven to reduce trial expenses and increase efficiencies, and its use should continue to grow in the coming years.