The Evolution of Risk-Based Approaches in Clinical Trials

As the complexity of clinical trials continues to escalate, risk-based quality management (RBQM) is no longer just an innovative approach—it’s a necessity. The clinical research landscape is transforming rapidly, driven by globalization, regulatory pressures, and advances in technology. For organizations involved in clinical trials, navigating these changes requires adopting new strategies, particularly risk-based methodologies, to maintain efficiency, enhance data quality, and optimize resources. 

The Growing Complexity of Clinical Trials 

The sheer number of clinical trials is growing exponentially. In 2000, there were approximately 2,100 clinical trials registered globally. As of April 2024, that number had ballooned to over 491,000.¹ Alongside this surge is increasing complexity of trial management, which now includes managing a larger volume of data, more regulatory requirements, and a globally dispersed set of trial sites. 

As clinical trials spread across more sites, including emerging regions, organizations face rising costs in sending clinical research associates (CRAs) around the globe for on-site monitoring. Moreover, the siloed, traditional approaches that many organizations follow often fail to holistically address the evolving needs of today’s trials. This is where risk-based approaches, particularly RBQM, come into play. 

The Benefits of Risk-Based Quality Management 

Risk-based quality management is not new—it has been evolving since the late 1980s when the FDA introduced its first guidelines on monitoring clinical investigations. The foundational guidance, particularly ICH E6 and ICH E8, established clear steps for integrating risk management into clinical trials. However, RBQM has gained significant momentum in recent years due to its demonstrated ability to improve trial outcomes. 

A study by the Tufts Center for the Study of Drug Development pointed to the potential for RBQM to increase efficiency, speed, and quality in clinical trials.² By identifying and mitigating risks early in the trial process, organizations can reduce downstream issues, particularly in later-stage trials, where delays can be especially costly. This systematic approach to risk management helps organizations avoid critical errors and optimize their resource allocation, ensuring that efforts are focused on the most impactful areas.

Key Principles of RBQM 

At the heart of RBQM is the identification of critical to quality (CTQ) factors—both critical processes and data—that must be protected throughout the trial lifecycle. These CTQ factors are essential to patient safety, data integrity, and regulatory compliance. The guidance provided by ICH E6(R2) and E8(R1) emphasizes the importance of prioritizing resources and applying proactive communication to manage these risks effectively.

The RBQM process can be broken down into seven key steps: 

1. Identify Critical to Quality Factors: Early in the trial, identify the processes and data that are essential to the trial’s success. 
2. Identify Risks: Analyze potential risks at both the program level and the study level. 
3. Evaluate Risks: Assess the severity and likelihood of each risk and develop mitigation strategies. 
4. Control Risks: Implement systems to monitor and manage risks throughout the trial. 
5. Review: Continuously review the effectiveness of the risk management strategies. 
6. Communicate: Ensure that all stakeholders are kept informed of risks and mitigation actions. 
7. Report: Document all risk management activities for compliance and future audits. 

Adapting to Modern Challenges 

The evolution of clinical trials brings unique challenges, including the growing volume and variety of data, protocol amendments, the rise in the number of investigational sites, and the integration of advanced technologies. Traditional methods, such as full SDV (Source Data Verification), have proven insufficient and have not added significant value to trial outcomes. Therefore, risk-based approaches are critical for managing these modern challenges. 

One of the key advances driving the adoption of RBQM is the integration of technologies that enable centralized monitoring and real-time data analytics. These technologies allow for remote oversight of clinical sites, reducing the need for on-site visits, and provide sponsors with faster insights into trial progress. The adoption of electronic health records (EHR) beyond the electronic data capture (EDC) system has further streamlined data collection, enhancing the efficiency and accuracy of trials. 

Embracing a Phased Approach to Implementation  

For many organizations, the transition to RBQM can be daunting. To ease this transition, at eClinical Solutions, we recommend a phased approach offering a manageable pathway to full integration. Our phased model begins by establishing Critical to Quality (CTQ) factors and basic risk management protocols, then progressively adds oversight and centralized monitoring capabilities. By taking incremental steps, organizations can achieve quick wins while building the necessary infrastructure and processes to set the stage for more comprehensive RBQM implementation.

Best Practices and Critical Success Factors 

Beyond this phased approach, successful RBQM implementation also requires a foundation of best practices and attention to critical success factors. Importantly strong executive sponsorship ensures top-down alignment and the right resources to drive transformation. A change management framework incorporating structured training and proactive communication builds support for re-engineered processes that fully align with RBQM principles rather than adapting outdated workflows.  And by promoting cross-functional collaboration and defining robust business objectives upfront, organizations can break down silos and enhance risk management effectiveness at every phase.  Finally, an end-to-end technology solution is key, integrating centralized data governance, traceability, and real-time monitoring to deliver the insights needed for proactive, informed oversight.

The Future of Risk-Based Approaches: ICH E6 (R3) and Beyond 

The ongoing evolution of regulatory guidance, particularly the forthcoming ICH E6(R3), underscores the increasing focus on risk management in clinical trials. The new guidance, emphasizes a more nuanced approach to risk management, including proportional actions based on the level of risk. This shift reflects the growing need for adaptable, fit-for-purpose strategies that can be customized to the specific needs of each trial. 

ICH E6(R3) also highlights the importance of data management and audit trail monitoring, ensuring that all systems used in clinical trials are designed to capture and maintain the integrity of the data. This shift toward more granular oversight is a response to the increased complexity of modern trials and the rising importance of data as a critical asset in clinical development. 

In conclusion, RBQM is no longer optional for clinical trial success—it is an essential part of our toolkit for navigating the growing complexities of modern clinical research. By taking a strategic approach to adopting risk-based methods, organizations can improve trial efficiency, ensure data integrity, and enhance patient safety, ultimately driving better outcomes for clinical development. 

To discover how elluminate RBQM enables sponsors to proactively manage risk across the trial lifecycle, click here:  https://www.eclinicalsol.com/products/risk-based-quality-management/ 

To catch up with our recent SCDM webinar, Navigating Trial Complexity with RBQM: Practical Strategies for Adopting Risk-Based Approaches: 

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References

¹ https://www.statista.com/statistics/732997/number-of-registered-clinical-studies-worldwide/#:~:text=The%20number%20of%20registered%20clinical,just%202%2C119%20registered%20in%202000. 

² Dirks A, Florez M, Torche F, Young S, Slizgi B, Getz K. Comprehensive Assessment of Risk-Based Quality Management Adoption in Clinical Trials. Ther Innov Regul Sci. 2024 May;58(3):520-527. doi: 10.1007/s43441-024-00618-5. Epub 2024 Feb 16. Erratum in: Ther Innov Regul Sci. 2024 Sep;58(5):996. doi: 10.1007/s43441-024-00648-z. PMID: 38366107; PMCID: PMC11043178.