A point-of-view summary of a pharmaceutical presentation.
In the clinical trial industry, ensuring quality is of utmost importance and is a concept that has gained popularity in recent years. I attended a presentation at SCOPE 2023 by Esther Huffman O’Keefe, Director of Adaptive Monitoring Excellence at Takeda Pharmaceuticals, discussing quality by design (QbD) approaches versus traditional monitoring methods. All opinions expressed in her presentation are her own and do not represent Takeda. This report is a summary of my interpretation of O’Keefe’s presentation.
O’Keefe believes QbD fosters a culture that values critical thinking and promotes dialogue about quality, rather than relying solely on checklists and tools to manage and monitor clinical trials. This approach is aligned with the most recent guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and regulators.
O’Keefe emphasizes the importance of ensuring that quality is built in at all levels of study planning and conduct. Identifying quality elements prospectively, and periodically reviewing critical to quality factors is crucial. O’Keefe suggests that considering end-to-end quality and incorporating quality at every opportunity dramatically increases the probability of generating data needed to determine whether study endpoints are met.
Evidence indicates that retrospective monitoring is insufficient to ensure the quality of the study by itself. In O’Keefe’s definition, quality is the absence of errors that matter, specifically the absence of errors that would matter to decision-making – which is admittedly difficult to measure. Quality-focused site monitoring should focus on subjects’ safety, rights, and protection, ensuring integrity in the reported data, and confirming that sites’ performance complies with protocol and regulatory requirements.
O’Keefe argues that traditional monitoring approaches may not achieve quality, such as a single individual performing 100% Source Data Verification (SDV) on-site. Literature indicates that intensive traditional monitoring does not significantly identify either critical errors in data or protocol deviations, so this legacy monitoring approach does not support quality goals. O’Keefe suggests instead that targeted review of critical data is a more effective approach for quality management, and that focusing on data-driven issue resolution is key to successful quality outcomes.
Protecting data quality involves more than simply using centralized monitoring tools. Instead, O’Keefe suggests adopting a cross-functional, risk-based monitoring approach that focuses on identifying and resolving the errors that matter rather than just cleaning or identifying signals in data. She stresses that all roles in a trial should be responsible for monitoring, and any monitoring should be intentional and data-driven.
Measuring quality is difficult, but O’Keefe considers quality in every aspect of the clinical trial process, including monitoring. She believes quality and monitoring strategies should be a top priority in the industry, even if they are difficult to quantify.
In conclusion, Esther Huffman O’Keefe emphasizes the importance of fostering a culture that values critical thinking and promotes dialogue about quality in clinical trials. Adopting a cross-functional, risk-based monitoring approach that focuses on the quality of the data is crucial. All roles in a trial should be responsible for monitoring, and any monitoring should be intentional and data-driven. Quality and monitoring strategies should be a top priority in the industry. Ensuring that studies produce good quality outcomes is more likely when leveraging data-driven risk-appropriate models.
Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and regular contributor to Applied Clinical Trials.