- The standards for monitoring trial conduct have changed significantly since 2013. The current “Gold Standard” of frequent onsite visits and 100% Source Data Verifications (SDV) for quality oversight of clinical trials is no longer sufficient. The FDA and EMA (Regulators) have signaled that they expect a change in trial oversight to an approach called Quality by Design1,2; a methodology the auto industry and pharmaceutical manufacturing have used for many years. Regulators expect that clinical trial oversight will move to a more “Risk-based” approach, focusing on the most important areas of trial conduct: subject safety, protocol compliance, Investigational Product Oversight, and Good Clinical Practice (GCP). The industry has adopted a name for it - Risk-Based Monitoring (RBM).
Numerous articles have been published showing the inadequacy of SDV as a method of trial quality oversight and it is not recommended as the preferred approach to trial quality by TransCelerate BioPharma (a consortium of major Pharma Companies).3,4
- The term Risk-Based Monitoring is NOT about decreasing Source Data Verification (SDV) and monitoring visits—it is about using a comprehensive approach to focus oversight on the most important aspects of the trial and subject safety. This includes:
- Identifying and classifying potential trial risks across key areas: efficacy, safety, GCP, Investigational Product Management, and protocol compliance.
- Monitoring for identified risks starting as early as possible after a subject visit.
- Instituting an issue management approach to capture issues, evaluate its scope, determine root cause, institute remediation, and follow through to assure the issues are resolved.
- Risk-Based monitoring should be instituted in all trials. In most cases when monitors use SDV, they look at each subject’s forms in isolation (see figure below). They review the vital signs for one subject and one visit, then move to another form and repeat the process. It is almost impossible to identify trends using this approach or even see if the data make sense from one form and one visit to another.
With RBM, Monitors should conduct a comprehensive Source Data Review, which should include all data sources for the trial (e.g., the clinical data, patient reported outcomes, labs). RBM should also include a data review across subjects to identify consistent errors across all subjects in a trial and a review of all sites to identify outliers.
483’s have been issued to major Pharmas for missing consistent errors across research subjects5,6,7.
- RBM may save you money. The Regulators have recommended more review be done faster and remotely—optimizing the use of technology. Fewer monitoring visits decreases travel costs, however, monitors will need additional time to conduct more comprehensive reviews. This additional review enhances the quality of the data, lowers risk to research subjects, and enhances the likelihood of the data being accepted by Regulators. RBM, however, may not save as much in monitoring time as originally anticipated when the RBM guidance was first released.