LANDRICH GROUP
Risk-Based Monitoring: Challenges and Opportunities
Since the COVID-19 pandemic, clinical trials have transitioned from traditional monitoring methods towards a more flexible approach known as Risk-Based Monitoring (RBM). RBM offers a potential paradigm shift in the speed, efficiency, and costs for bringing new therapeutic, medical device, and diagnostic products to market.
Drug and medical device development budgets face intense pressure, with US health care spending predicted to reach 20% of US GDP in the coming decade, driven by an aging population. Supply-side innovations that lower the cost of trials will inevitably attract strong interest. Clinical firms that successfully operationalize RBM acquire a key competitive advantage.
Traditional monitoring processes, such as 100% Source Data Verification (SDV) and Source Data Review (SDR), are the single biggest cost driver in many trials. This practice entails extensive visits to compare data entering in Case Report Forms (CRF) with original onsite source documentation such as patient records and lab reports. Multiple studies show the potential for cost savings and improved quality:
- A study in the American Heart Journal further demonstrated the gaps in SDV from a cost and quality perspective. This study developed 2 case scenarios for trials involving cardiological drugs and surveyed pharmaceutical experts on required resources using the SDV methodology. These sources provided estimates using SDV that required over 50% of site monitoring budgets, with 50% of total time and effort dedicated to carrying out the SDV on-site.
Background
The earliest reported use of traditional SDV monitoring dates to 1746, when the British Navy was assessing citrus fruits for prevention of scurvy in the world’s first known clinical trial. The process was highlighted within an FDA policy in 1998 that effectively mandated in-person verification of every single piece of data submitted at any site to the trial sponsor. The agency relaxed this requirement in 2013, encouraging an RBM model like the European Union (EU) that focused on channeling resources and onsite activities to high-risk priorities. Despite the FDA’s endorsement of RBM more than a decade ago, industry surveys show that clinical teams were slow to adopt risk-based strategies before the COVID-19 pandemic made remote monitoring necessary.
A 2024 study of over 200 companies by Tufts Center for the Study of Drug Development found that 57 percent of their clinical trials were implementing some risk-based protocols, which concentration higher in early stages like documentation, planning and design. European companies had significantly higher adoption than the rest of the world (i.e., 64% versus 45% elsewhere). Industry observers agree there’s still plenty of room to increase RBM utilization for increased trial efficiency and cost reductions.
ICH E6(R3) is a globally accepted Good Clinical Practice (GCP) released in early 2025 aligns with the shift to RBM by emphasizing risk-proportional approaches to Quality Management through clinical trial lifecycles. The new GCP Guideline also encourages agility on how acceptable ranges for quality are implemented instead of more rigid Quality Tolerance Limits, establishes clearer roles and responsibilities, and promotes collaboration to meet quality objectives of clinical studies.
Getting Started
In spite its obvious benefits, many organizations are still avoiding or narrowly confining use of risk-based monitoring plans in their clinical research. This can be a significant cultural change, with unknown unknowns for an inexperienced team. The term RBM itself puts the issue of risk front and center, potentially exacerbating anxiety around uncertainty.
These reasons for reservation may be understandable, but they should not prevent clinical teams from embracing a phased approach because RBM will become increasingly indispensable in the coming decade. Any organization that is not actively re-imaging their end-to-end process for risk-based efficiencies will be at a competitive disadvantage.
Here are some early- stage activities for companies embarking on the transformational journey to RBM:
1. Establish a Cross-Functional Team
Form a dedicated team with representatives from various departments such as clinical operations, product development, data management, biostatistics, regulatory affairs and quality assurance to lead the strategy.
2. Conduct Education and Training
Invest in comprehensive training programs to build a risk-based culture within the organization, requiring participation of sponsors, site personnel, CROs and other key stakeholders.
3. Start with a Pilot Study
This allows the organization to demonstrate the effectiveness of Risk Based Quality Management (RBQM)on a smaller scale, focusing on critical to quality (CTQ) factors and key risk indicators (KRIs).
4. Identify Critical Processes and Data
Identify early on the processes, data, and Key Performance Indicators (KPIs) that are essential to clinical trial success.
5. Conduct a Comprehensive Risk Assessment
Perform a thorough risk assessment analyzing all factors at the program and study level, such as the nature of the intervention, study population characteristics, and the research team's experience.
6. Develop a Risk Mitigation Plan
Based on the risk assessment, create strategies to reduce or eliminate identified risks. This should include determining actions, triggers for intervention, and contingency plans
7. Implement Appropriate Technology
Utilize risk-based monitoring software solutions to facilitate risk assessment, mitigation, and reporting. This ensures a consistent, data-driven approach to risk management.
8. Seek Guidance and Feedback from Regulators
It is important to communicate clearly and pro-actively with your regulatory partners. Demonstrate your familiarity and compliance with existing regulations and GCP guidelines. Provide detailed documentation and illustrate how a data-driven approach to monitoring and decision-making. Request feedback on your risk assessment methodologies, monitoring strategies, and data management approaches both early on and iteratively throughout the process.
By taking these initial steps, organizations can begin to shift their clinical trial management framework towards risk-based principles, setting the foundation for more efficient, quality-focused, and patient-centric clinical trials.
Appendix:
How does RBM differ from SDV on the ground? Here are a few of many potential scenarios:
Resources:
SDV: Monitors would visit all sites regularly, spending equal time at each regardless of performance.
RBM: More resources and attention would be directed to high-risk sites identified through data analytics, while well-performing sites would receive less frequent visits.
Data Verification:
SDV: 100% of source data would be verified on-site for all patients.
RBM: Only critical data points would be verified, with a focus on high-risk areas identified through centralized monitoring.
Issue Detection:
SDV: Problems might only be discovered during scheduled on-site visits.
RBM: Centralized monitoring would allow for real-time detection of data anomalies or safety concerns, enabling faster interventions.
Protocol Deviations:
SDV: All deviations might be treated equally.
RBM: Deviations would be categorized by risk level, with resources focused on addressing critical issues.
Landrich Group advises clients in the development and application of risk-based monitoring strategies, with a focus on FDA approval of trials for In Vitro Diagnostics and Companion Diagnostics. For more information on supporting your RBM needs, please contact us at admin@landrichgroup.com
