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Clinical trial quality has changed after the pandemic. Sponsors are following new regulatory guidances on creating a “culture of quality,” and having access to near real-time data are revealing novel ways of overseeing clinical trials. Sheri Kuss, clinical quality group lead at Pfizer, evangelized her perspectives at Momentum Events’ Clinical Quality Oversight Forum.
Moe Alsumidaie: How has clinical trial quality changed in today’s environment?
Sheri Kuss: Risk management and quality tolerance limits (QTLs) are critical areas of discussion. I'm impacted daily by the speed of science, and I think we've all benefited from it, but how do we demonstrate oversight? Auditors like to look at events and their root causes. Do we have a process? Do we have a strong, robust quality management system, training SOPs, risk management plan development, and quality tolerance limits? Looking at study conduct to see if there is noise or real quality concerns is vital in today's environment because you have to answer these questions rapidly and comprehensively. Having near real-time access to data helps immensely.
MA: How are quality events managed?
SK: We look at quality events related to subject safety, subject rights, and data integrity. Triaged into different levels, levels 2 and 3 get cross-functional team investigations, and I attend these events to monitor trends and risks. I look at trends, quality events, and audit findings to connect dots and share information broadly. Everyone knows and owns quality, so it’s certainly embedded in our culture. Still, in our meetings, my ears perk up every time I hear my colleagues mention risk. Of course, not all risks are created equal, so I have to distinguish between operational and quality risks. We often build storyboards for our more complex issues and these storyboards stay behind the scenes. We're not just focusing on particular issues, we are evaluating whether the problems are systemic and if the CAPAs are effective. We also try to improve on efficiency whenever possible: as an example, we maintain the same team members when investigating events since they have built a knowledge base regarding the study.
When it comes to risk management, one of the things that we've done well is that we're bringing risk management issues up daily and/or weekly and talking about them and the potential cross-functional impact. We start by focusing on the following: what's a risk for the study, what is the potential impact, and can we mitigate it effectively? Quality professionals are conservative, and we are risk-averse typically. When working at light speed, the best thing to do is to get in front of the risks before they become issues, if possible. Naturally, you can't stop all events from happening. Still, if you're looking at risks across the board, there will be ambiguities, and it is critical to investigate and question these ambiguities on a more granular level. We've challenged and adapted our risk management plans several times throughout the life cycle of a study because we want to get it right. These are often impacted by protocol amendments, quality events, deviations, and the region's risk level, to name a few.
MA: How has the pandemic impacted perspectives on quality?
SK: We were very conservative, given the pandemic-driven virtual situation we were in, which was a good mindset to have, especially since there were so many unknowns at the time. We put prospective control measures in place cross-functionally and kept open lines of communication. I'm especially impressed with our teams' performance and engagement throughout the risk management process. For example, our teams give a lot of thought about study design as it pertains to quality elements such as participant participation and compliance. The study design and participant experience must be talked through so that risks can be evaluated rigorously.
MA: Do QTLs have to be adjusted when amending protocols?
SK: QTLs have to be closely monitored during the study and adjustments may be needed, especially when a protocol amendment is issued. A significant compliance risk is when there are multiple protocol amendments within a study, which potentially has many complicating factors. It is naïve to think that amendments are issued with minimal impact to study conduct, documentation, compliance, and monitoring of data. The reality is that downstream effects potentially could be enormous. For example, just related to QTLs, you may have to adjust the QTL parameter, definition, threshold, monitoring of them and possibly the mitigations based on the changes.And, if it's not clearly documented, then it could be a question internally or with regulators. We need to get in front of anticipated risks by building tools, tips, having access to near real-time data, sharing lessons learned and creating storyboards.The more we can do these things prospectively and share lessons learned from similar situations or studies, the better off we are.
MA: How has near real-time access to data changed clinical trial quality oversight?
SK: We have a custom-built dashboard focused on Quality data. This dashboard has historical and near real-time data. Accessing a dashboard with up-to-date data at my fingertips has been transformative. Connecting dots early has been impactful in programs that run quickly. I examine events and look for potential trends. If we have that data, we can mitigate risks much faster. Very simply, if something happened at one site and seems as if it could happen elsewhere, I'll share it and ask if we have strong enough mitigations to prevent it from happening more broadly. If we can apply mitigations broadly, then our CAPAs could span across multiple studies, programs, or even therapeutic areas. I like to share lessons learned, and assess the trends and effectiveness checks to see if what we have implemented has worked.The more quality data we have access to, the more we can try to intervene early and/or prevent the same things from happening again.