Let’s face it – traditional on-site monitoring is becoming obsolete. Given the complexity of today’s global, multi-site clinical trials landscape, traditional site monitoring can be an inefficient method to ensure patient safety.
And with site monitoring costs running close to 10 to 15% of total study budget with 100% monitoring (costing as much as $1 million to $5 million), it will certainly pay to review and improve this area of study design.
A new methodology is necessary to answer the following questions:
- How do I determine which monitoring practice will be appropriate for a given clinical trial?
- How can I leverage technology advances to allocate limited resources to high impact activities?
Risk-based monitoring (RBM)
The new industry best practice, led by the U.S. Food and Drug Administration, is known as “risk-based monitoring” (RBM). It aims at better assessing risks to tailor the monitoring plan to the needs of the trial. The risk-assessment phase takes place before the protocol is finalized and is performed by a cross-functional group involving various roles and team members (e.g., Data Managers, Trial Monitors, Clinical Scientists).
Assessing risks implies a proactive approach. All study-related elements, including complexity of the study design and population, types of study endpoints, number and location of sites involved, and technologies available (electronic data capture) should be taken into account and evaluated. Overall, good performance of your risk assessment will undoubtedly result in increased patient safety and a more efficient clinical trial process.
Based on insights from your risk assessment, you can then better develop your monitoring plan. This is precisely why it is known as a “risk-based monitoring plan”. It is an adaptive approach to clinical trial monitoring, where the team must focus on the areas of greatest need – in other words, those areas that have the biggest impact on patient safety and data quality.  This facilitates early risk identification, regulatory compliance and fast responsiveness.
Risk indicators, thresholds and critical data and processes are used to determine the frequency of monitoring activities, the type of monitoring (on-site or centralized), and the action plans required (the statistical analysis plan, the safety plan, the quality plan, etc.).
The electronic Trial Master File (eTMF) and centralized monitoring
Centralized monitoring is becoming the norm. This is a “remote evaluation carried out by sponsor personnel or representatives (e.g., Data Manager, Statistician or Monitor)”. It allows for a remote appraisal of the study data, resulting in a great timeline gain and reduced costs for larger, multi-country sites.
But a successful implementation of centralized monitoring requires effective planning and having the right technology in place. All essential documents must be available at all times. In this context, leveraging your electronic Trial Master File (eTMF) (or putting one in place) can greatly enhance the efficiency and effectiveness of your risk-based monitoring.
Investigator’s brochures, signed protocols, amendments, patient consent forms, and certificates of analysis are only a few examples of the documents that are tracked in an eTMF. The eTMF allows for remote and real-time follow-up, enabling quicker intervention and implementation of targeted on-site monitoring. The number of on-site visits is significantly reduced, thereby drastically lowering the cost of the clinical trial.
By using the right methodology and the right technology, key stakeholders can focus on critical processes, data quality and regulatory compliance, ensuring risk mitigation, early issue detection, and increased patient safety. Adoption and mature use of an electronic Trial Master File during study conduct is a significant step in realizing an efficient and effective approach for risk-based monitoring, ensuring decrease of overall study cost and compliance with the latest Good Clinical Practices. It also ensures that you focus your monitoring activities on the right sites to mitigate compliance issues and shorten the study conduct timeline.
If you don’t already have an eTMF in place or would like to continue the conversation about risk-based monitoring, we would be pleased to hear from you – contact Mathilde Chevallier.
 Risk-Based Monitoring Overview, TransCelerate BIOPHARMA INC.
 FDA Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring