A conversation with Steve Young, member of Avoca Quality Consortium, PHUSE Working Group participant, and Tufts survey contributor
As Good Clinical Practice Guidelines look cement support for risk-based quality management (RBQM), an international industry-wide survey has found that 45% of research organizations have yet to start their risk-based journey.
The approach shifts emphasis away from manual, time-consuming, and error-prone 100% source data verification (SVD) and on to “critical to success” processes and data points. As such, it has the ability to accelerate trial timelines and improve data quality.
So where are the gaps between ambition and reality, and what still needs to be done to make higher quality, more efficient, and faster clinical trials a reality?
Here, Steve Young, member of Avoca Quality Consortium, PHUSE Working Group participant, and Tufts Impact Report contributor, discusses the findings of the groups’ joint global research study with CluePoints and Price Waterhouse Cooper (PwC), the implications of the upcoming ICH E6(R3) guidelines, and the future of risk-based clinical trial conduct.
1. What does ICH E6(R3) say about RBQM?
Young: ICH E6(R3), the final draft version of which was published in May, emphasizes the importance of RBQM as part of good clinical practice (GCP). It ties the concepts of quality by design (QbD) and RBQM together to create a holistic, end-to-end clinical trial methodology.
The concept of RBQM has evolved from risk-based monitoring, first recommended by the FDA in its guidance on RBM published in 2013, which focused primarily on applying risk-based approaches to site monitoring alone. It shifted the emphasis from resource-intensive, human error-prone 100% source data verification to the centralized monitoring of those data that are most critical to trial quality. Since then, it has become clear that the quality- and efficiency-boosting advantages are not limited to site monitoring. Indeed, all areas of study operations, from setup to execution, stand to benefit.
ICH E6 (R3), which is currently subject to public consultation, now more explicitly recommends QbD and defines the proactive identification of factors (such as data and processes) that are critical to trial quality. It also advises organizations to implement strategies to “avoid, detect, and address serious non-compliance with GCP, the trial protocol, and applicable regulatory requirements” across the clinical research continuum.
Risk mitigation activities may be incorporated in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, systematic safeguards to ensure adherence to SOPs, and training in processes and procedures, the document says. The sponsor should set acceptable ranges to support this process and any detected deviation beyond these ranges should prompt an evaluation and any necessary corrective action.
One thing worth mentioning is that the draft document no longer includes the term “quality tolerance limits” (QTLs), replacing it instead with the term “acceptable ranges.” The introduction of QTLs in ICH E6(R2) has driven a significant level of discussion across the industry to develop a common understanding and best practices for QTL adoption. This proposed update is already drawing a lot of attention and questions are being raised regarding the intent and implications. While these questions are important to address, it is also somewhat reassuring to note that the core concept and expectations are largely retained in the proposed R3 update.
By recommending risk assessment, risk mitigation planning, and on-study risk detection, ICH E6(R3) reinforces the idea that risk-based approaches should be part of the holistic paradigm of clinical trials.
2. What does the Tufts study tell us about the current RBQM landscape?
Young: The survey collected responses from 206 representatives of pharma, biopharma, and CROs on 31 individual RBQM components.
Contrary to previous studies that have reported that around 70% to 80% of organizations had already started their RBQM journey, just 55% reported that they had adopted RBQM.
There was some variation in the stage at which these approaches had been introduced. The highest, 60%, was for documentation and resolution, while the lowest, 51%, was in the execution arena. It shows that universal adoption of the end-to-end RBQM approach recommended in ICH E6(R3) is still some way off.
It was also interesting, though perhaps not surprising, to find that mid- and large-sized pharma organizations have been leading the way in terms of adoption (58% to 60%), with smaller companies being less likely to adopt the approach (47%). During a series of roundtable discussions, it was observed that smaller organizations often have fewer resources available to focus on implementing new processes such as RBQM.
3. How can we bridge the gap between the end-to-end RBQM spirit of ICH E6(R3) and current levels of adoption?
Young: When our survey asked about barriers to adoption, respondents cited factors relating to internal change management. These included a lack of cross-function awareness (69%), the investment of time to implement (48%), a shortage of necessary skills (47%), and a lack of cross-function consensus (38%).
As such, organizations would do well to educate all business functions on the practicalities and the benefits of RBQM to secure buy-in and ease the adoption process. Events such as RBQMLive, for example, bring the leading figures in the discipline together to discuss its rationale and implementation. This can be enhanced by starting with simple changes, such single RBQM elements, rather than implementing multiple complex changes all at once. For example, RBQM components such as pre-study risk planning and/or central monitoring can be implemented — and add significant value — even if an organization is not yet ready to move away from traditional on-site monitoring including 100% SDV.
The survey’s study of RBQM perceptions also revealed a need for further education. A total of 83% of respondents said their organization was committed to implementing the approach. Of these, 78% said they trusted that it would improve quality, and 63% trusted it would improve efficiency and costs. However, just 53% trusted it would reduce timelines.
Our roundtable talks also highlighted that there is some work to do around definitions. While some representatives spoke of RBQM as being a single element, centralized risk monitoring for example, others felt it covered the full clinical trial continuum. As ICH E6(R3) reinforces the idea of RBQM as an end-to-end study methodology, it takes us a step closer to a universal definition, which will only help with adoption going forward.
About The Expert:
Steve Young is a member of Avoca Quality Consortium, PHUSE Working Group participant, and Tufts survey contributor, as well as chief scientific officer for CluePoints. Steve oversees the research and development of advanced methods for data analytics, data surveillance, and risk management, along with guiding customers in RBQM methodology and best practices. Steve worked for three biopharmaceutical companies over 15 years, where he assumed leadership positions in clinical data management and led the successful enterprise rollout of EDC at both J&J and Centocor. He spent an additional six years with eClinical solution providers Medidata and OmniComm, leading the development of analytics and risk-based quality management (RBQM) solutions and providing RBQM consultation to many organizations. Steve also led a pivotal RBM-related analysis in collaboration with TransCelerate and is currently leading RBQM best-practice initiatives for several industry RBM consortiums. Steve holds a master’s degree in mathematics from Villanova University.