It’s hard to believe that nearly five years have passed since the FDA published its guidance for industry on risk-based monitoring (RBM).
Like all new initiatives, there were early adaptors but it’s fair to say that for the first few years RBM was a slow-burner. However, in the intervening period the landscape has changed and with the introduction of ICH GCP E6 (R2), RBM is now becoming an expectation rather than a suggestion. In parallel, sponsor companies and CROs have also made great strides in adapting their operating models, organizational structures, and contractual relationships to enable RBM to become mainstream.
A Quick Recap - What is RBM?
Studies have shown, and it is now widely accepted, that the traditional site monitoring approach of on-site visits and 100% source data verification (SDV) does not necessarily result in higher data quality or mitigate against trial delays or issues.
Monitoring a targeted subset of the data via a targeted monitoring strategy, using a reduced SDV strategy focused on critical data, patient visits, and/or selected patients based on the risk profile of the trial can be a more beneficial approach. Full RBM goes one step further and allocates monitoring resources to the areas of greatest risk and need, using sophisticated centralized data review approaches that support confident rapid decisions and interventions.
Centralized monitoring is at the core of every RBM strategy, but RBM takes the quality control and auditing benefits of centralized monitoring and makes the process more efficient, agile, and cost-effective.
At its simplest, an RBM approach comprises three components:
- Planning and risk assessment
- A project-specific monitoring plan
- Centralized, risk-based, data-driven review of data
Identifying and mitigating risks is the most important step in any clinical trial and central to ICH E6 R2, but successful implementation of RBM depends on doing this well. If you have a true understanding of where the main risks for your study lie, you can develop a comprehensive monitoring plan based on the key risk indicators and performance metrics you identify upfront. The capability to monitor these risks has been hugely enhanced with the help of robust and cutting-edge technologies. Today, state-of-the-art EDC and DDM platforms can integrate different data types and sources, handle large volumes of data, review and analyze the data to identify trends, patterns and outlines, and provide visual representations that easily identify risks or issues. These tools provide data in intelligent ways, spotlighting key performance indicators and revealing trends and issues in real-time.
Results to date
Organizations that have adopted RBM have demonstrated that a well-implemented RBM system:
- Identifies problems early and facilitates quick remediation, thereby protecting patients and preserving data integrity
- Improves the efficiency of CRAs, directing resources to the sites that most need help
- Significantly improves data reliability
However, as those of us in the clinical research industry are only too well aware, all interventions, even positive ones such as RBM, inevitably introduce side effects. In the case of RBM, some sites perceive that its introduction has resulted in a greater burden and a loss of personal touch.
Oversight AND Engagement
At Longboat, we believe this technology revolution shouldn’t stop with data integration and analytics, but must also focus on site engagement, communication, continuous learning, facilitating protocol compliance, and even earlier recognition of problematic sites.
Clinical trials are dynamic, so training and resources deployed need to be adaptable throughout the study. For example, protocol amendments and targeted support for underperforming sites need to be rolled out quickly and consistently as the study progresses. Making sure that sites have the knowledge and training that they need and tracking the use of resources developed for their specific protocols can be extremely useful to monitoring teams under an RBM methodology.
It’s clear that RBM can add value by improving efficiency, supporting patient safety, protecting data integrity, and potentially reducing costs. The evolution of risk-based approaches comes with the need for improved communication and relationships between investigator and sponsor, to ensure that clinical trials make the most of new technology, but are run by real people, for real people. Combining transparency and oversight with the means to engage, communicate and implement the necessary corrective actions at sites closes the RBM loop.