The Florence team just got back from the MAGI conference where we spoke on clinical trial site operational efficiency and the impact that monitoring queries have on sites. In our session and throughout the conference we heard the question: What is the difference between Risk-Based, Remote-Based, and Centralized Monitoring in clinical trials?
Monitoring is an FDA-mandated process whereby the integrity of the clinical trial process is validated. The validation process includes site visits to inspect personnel, facilities, equipment, processes, and source and regulatory documentation.
Validation is a huge amount of work, and historically, hugely personnel-intensive. The contract research organization (CRO) industry emerged to support this work with armies of monitors – at a great expense.
Specifically, monitoring is estimated to be about 1/3 of any prospective clinical trial operating budget. For an industry that spends over $30 billion on clinical trials, this means over $10 billion is spent each year on monitoring. So starting in 2011, the FDA issued guidance on modifications to this process, in an effort to encourage faster and less costly practices. Now, five years later, there’s still confusion around the options available to a sponsor for making this process more efficient. Each option deals with either reducing the scope of verification or making it easier on both the site and the sponsor.
- Targeted Risk-Based Monitoring: focuses on certain data points, certain sites, and certain events that may have the most risk and argues that validating them will produce the best value for the time and resources invested. These areas of focus are usually defined before the trial begins.
- Triggered Risk-Based Monitoring: occurs when certain events (like a large number of adverse events, deviations to protocol) trigger detailed monitoring of particular endpoints or sites.
Remote Monitoring vs. Centralized Monitoring
- Remote Monitoring: allows pharma and CROs to remotely conduct monitoring activities that were previously conducted on-site. This includes delivering documents to a CRA via email, fax, or snail mail to satisfy monitors’ queries and conduct source document verification.
- Centralized Monitoring: usually performed from the data collected via CRFs through electronic data capture (EDC). Allows the identification of outliers or trends that may need attention from the sponsor or CRO to identify and mitigate problems with the trial.
What’s the tradeoff?
These approaches either reduce the scope of verification or make the same level of verification more efficient for the site and the sponsor. Risk-based strategies have been implemented first—sponsors are simply verifying less data. Clearly, this carries the risk of missing critical issues. More recently sponsors are beginning to turn to remote strategies, which allow the same scope of verification but without the need for traveling to trial sites.
Remote monitoring has been challenging to date because the industry lacks the accessible infrastructure to allow HIPAA and 21 CFR Part 11 compliant access to patient records, regulatory documents, and trial master file content for monitoring. Florence is changing this by providing the industry’s first remote monitoring management system.