FDA Update on ICH E6, E8, QbD and RBM in Clinical Trials

The recent FDA workshop, “Building Quality into the Design and Conduct of Clinical Studies: Integrating Quality by Design (QbD) and Risk-Based Monitoring (RBM) Approaches,” brought together industry leaders, regulators, and stakeholders to discuss the integration of QbD and RBM in clinical trials. This event, co-convened by the Duke Margolis Center for Health Policy, emphasized the evolving landscape of clinical research, focusing on the importance of quality, integrity, and efficiency. The workshop aimed to provide a framework for improving the design and execution of clinical trials, ensuring they are both efficient and effective in meeting drug development challenges. Throughout this article, Dawn Niccum, Executive Vice President, QA and Compliance at inSeption Group will reflect on the workshop by adding her expert perspective.

Emphasizing Quality and Efficiency in Clinical Trials

The workshop placed a strong emphasis on the integration of QbD and RBM as pivotal methodologies for the modernization of clinical trials. Dr. Mark McClellan, representing the Duke Margolis Center for Health Policy, articulated the necessity of these approaches in enhancing the efficiency and effectiveness of clinical trials. He explained that QbD and RBM are not merely theoretical concepts but practical tools that facilitate the efficient management of risks inherent in clinical trials. These methodologies ensure that trials maintain high data integrity and participant safety standards by embedding quality throughout the clinical development lifecycle.

Applying QbD in clinical trials draws inspiration from best practices in manufacturing, where quality is built into the process from the outset. This approach, championed by leaders such as Janet Woodcock and her advocacy for QbD, stems from her belief that clinical trials should be designed with a clear focus on quality, leading to better outcomes and reduced costs. The workshop highlighted several case studies where QbD principles were successfully implemented, demonstrating tangible improvements in trial efficiency and data quality. For instance, one case study involved a pharmaceutical company that applied QbD principles to streamline its trial processes. By identifying critical-to-quality factors early in the design phase, the company was able to focus its resources on the most critical aspects of the trial, thereby reducing unnecessary complexity and cost. Another example illustrated how a clinical research organization used risk-based monitoring to identify potential issues early in the trial process, allowing for timely interventions that ensured data integrity.

These examples emphasize the potential of QbD and RBM to transform clinical trials, making them more efficient and effective. By focusing on these methodologies, the workshop provided valuable insights into how clinical trials can be improved to meet the evolving needs of the healthcare industry.

Incorporating Patient Voices in Clinical Trial Design and Decentralized Trials

A key theme of the workshop was the importance of incorporating patient perspectives into clinical trial design. Dr. Janet Woodcock emphasized the importance of patient input, noting that it can significantly enhance participant enrollment and retention. By involving patients in the planning stages of clinical trials, sponsors can design studies that are more aligned with participants’ needs and preferences, ultimately driving both quality and success. For example, one patient advocate highlighted the importance of flexible scheduling and remote participation options, making trials more accessible to more participants. Another advocate emphasized the need for clear communication and transparency throughout the trial process, which can help build trust and encourage continued participation.

There was also discussion on decentralized clinical trials. The COVID-19 pandemic accelerated the adoption of decentralized trial elements, such as remote monitoring and virtual visits, showing great potential to make trials more accessible and efficient. For instance, one trial used telemedicine to conduct virtual visits, allowing participants to remain in the study without frequent travel to clinical sites. Another trial employed remote monitoring technologies to collect real-time participant data, providing researchers with a comprehensive view of the trial’s progress.

The workshop highlighted that integrating patient perspectives and decentralized elements into clinical trial design enhances data quality by fostering greater participant engagement, accessibility, and real-time data collection, ultimately aligning studies more closely with participants’ needs and preferences.

ICH E6 and E8 Clinical Trial Frameworks and Harmonizing Global Guidelines

Discussions delved into the specifics of the ICH E6 and E8 guidelines, with the ICH E6 providing a framework for designing trials that are fit for purpose, ensuring that resources are concentrated on critical study aspects while reducing costs, and maintaining high data integrity and participant safety standards. The ICH E8 guideline, on the other hand, emphasizes the importance of a risk-based approach to trial design and conduct. By identifying and managing risks early in the process, sponsors can ensure that trials are conducted to maximize efficiency and minimize potential issues. For instance, one case study involved a multinational pharmaceutical company that applied the ICH E6 and E8 guidelines to a complex global trial. By focusing on critical-to-quality factors and adopting a risk-based approach, the company was able to streamline its trial processes and improve data quality. This approach reduced the trial’s overall cost and accelerated the timeline, allowing the company to bring its product to market more quickly.

The workshop also emphasized the global harmonization of good clinical practice guidelines, particularly regarding the recently published draft versions of ICH E6 and E8, designed to streamline clinical trial processes and improve outcomes. The workshop featured several case studies where these guidelines were successfully implemented, demonstrating their potential to transform clinical trial processes. For example, a representative from a global pharmaceutical company discussed how harmonized guidelines enabled them to conduct trials more efficiently across multiple countries, reducing the time and cost associated with meeting different regulatory requirements. Similarly, a regulator highlighted the benefits of harmonization in improving trial data quality and consistency, which is essential for making informed decisions about new treatments.

Inspection Readiness

Regulatory perspectives on inspection readiness and risk-based approaches were a key focus of the workshop. Jacqueline Corrigan-Curay, Principal Deputy Center Director in CDER, discussed the importance of integrating quality management principles into the design and conduct of clinical investigations. She emphasized the need for study-specific monitoring plans and a dynamic approach to continual improvement. The workshop featured presentations from regulatory experts and industry leaders, who shared insights on applying these principles effectively.

For example, one presentation discussed the role of technology in enhancing inspection readiness. By leveraging advanced data analytics and monitoring tools, sponsors can gain real-time insights into trial performance and identify potential issues before they become significant problems. This proactive approach improves the quality of the data collected and enhances the overall efficiency of the trial process.

The discussions emphasized the importance of a proportionate and risk-based approach to quality management tailored to the specific needs of each study. Sponsors can design more efficient, cost-effective, and likely-to-succeed trials by focusing on what matters most.

Challenges and Future Directions

Despite progress in integrating QbD and RBM approaches, challenges remain in fully implementing these methodologies. One primary challenge is the need for continued education and confidence-building among sponsors and regulators. Many stakeholders are accustomed to traditional trial processes and may hesitate to adopt new approaches without clear evidence of their benefits. The workshop provided a platform for discussing these challenges and exploring potential solutions, emphasizing the importance of training and resources to help stakeholders understand and implement QbD and RBM approaches.

The workshop highlighted the need for ongoing collaboration between industry, regulators, and other stakeholders to address barriers to adoption and ensure these modern practices are widely accepted and implemented. The FDA and Duke Margolis are committed to fostering an environment encourages innovation and efficiency in clinical trials. By continuing to promote QbD and RBM approaches, they aim to improve research quality and efficiency, ultimately leading to better patient treatments.

Conclusion

The FDA workshop was a platform for a robust discussion on modernizing clinical trials through QbD and RBM approaches. The event aimed to empower the clinical trial community to adopt these methodologies by sharing case studies and best practices, leading to more efficient, cost-effective, and high-quality research. As the clinical research landscape evolves, integrating these approaches will be crucial in meeting drug development challenges and delivering better patient treatments.

This article is sponsored by InSeption Group.