In this interview, I speak with Duncan Hall, CEO of Tritrials, about the importance of Risk-Based Quality Management (RBQM) in clinical trials, the challenges of implementing RBQM, and its future in the industry. We delve into the intricacies of building trust between sponsors and CROs and the evolving landscape of clinical trial management.
Moe Alsumidaie: Why is RBQM important in clinical trials?
RBQM is crucial because it increases efficiency, improves data quality, and enhances patient safety. Despite introducing RBM over a decade ago, many initial challenges remain unaddressed. The cost of clinical trials continues to rise, and the need for treatment is growing. Healthcare inequality is also increasing, as evidenced by the significant eight-year life expectancy gap between the wealthiest and least wealthy in the UK. RBQM can positively impact our ability to conduct more R&D per dollar than any other current initiative. It can save up to 25% of monitoring costs, reduce errors in critical data, improve protocol compliance, and provide earlier safety signals for trial participants. Regulatory authorities also emphasize the importance of ongoing quality management and risk-based approaches, as seen in the updates to ICH E8 and E6 guidelines.
The ICH E8(R1) revision and proposed changes to ICH E6(R3) are doubling down on risk-based approaches, highlighting the need for more innovative and more efficient methods. This regulatory push underscores the importance of RBQM in ensuring that clinical trials are conducted with the highest quality and safety standards. The increasing focus on these guidelines shows that RBQM is not just a passing trend but a critical component of modern clinical trial management.
Moe Alsumidaie: What are the key challenges you see with implementing RBQM across the sector?
Duncan Hall: The main challenges are no longer technical but human. RBQM requires cross-functional collaboration and a partnership between sponsors and CROs. It involves new roles, processes, technology, and a significant mindset change from routine monitoring to data-driven decision-making. This change management challenge is often not addressed adequately, leading to suboptimal implementation. Larger sponsors have had more success because they have the resources and budgets to manage this change effectively.
The ICH E6(R3) guidance makes it clear that the sponsor remains responsible for the conduct of the trial, including any activities that have been transferred to their service providers (CROs). This drives the need for trust but can also create opportunities for miscommunication and misunderstanding. During the COVID-19 pandemic, we saw examples where CROs claimed to have switched to a central and remote monitoring approach. Still, on closer inspection, there was little evidence of the core processes and technologies needed to be effective. This led to a breakdown of trust, and in one scenario, the sponsor decided to move RBQM in-house.
Moe Alsumidaie: What would you say to medium-sized and smaller biopharmaceutical companies about using RBQM in their clinical trials?
Duncan Hall: RBQM is not just for large sponsors and CROs. Smaller companies can also benefit from partnering with experienced CROs with a strong track record in RBQM. These companies should let experts guide them and ensure their chosen CROs can execute RBQM effectively. By doing so, they can achieve the same quality, safety, and efficiency benefits without extensive in-house expertise.
Smaller biopharmaceutical companies can look for CROs that have embraced RBQM and changed their organizational structure to support it. By conducting due diligence and selecting CROs with proven RBQM capabilities, these companies can leverage the expertise and technology of their partners to achieve successful outcomes in their clinical trials. This approach allows smaller companies to focus on their core competencies while benefiting from the advanced methodologies and technologies that RBQM offers.
Moe Alsumidaie: How can RBQM build trust between a sponsor and CRO?
Duncan Hall: We have developed a simple three-step model to help build trust, which involves making RBQM central to the relationship and ensuring transparency and visibility of key decisions and activities. The three phases of the model are Protocol Development, Quality Planning, and Study Conduct. During Protocol Development, the Sponsor initiates the risk assessment on an RBQM platform and shares the draft with the CRO. The CRO can then review and update the risk assessment, adding their risks if needed. This results in both parties having a shared view of what is critical for the study and the associated risks.
Evaluating and scoring those risks ensures a proportionate response in the Quality Planning phase. This involves agreeing on which RBQM components will be used, such as central monitoring, KPIs, QTLs, statistical monitoring, and other methods to manage quality. By capturing all this in the RBQM platform, both parties can openly communicate and agree on the thresholds and triggers for monitoring activities. During study conduct, regular central data analytical reviews and reporting observations and actions allow both parties to see the data, signals, and outcomes, enabling periodic reviews and adjustments. This continuous plan refinement ensures that both parties are aligned continuously and reduces the likelihood of unexpected events.
Moe Alsumidaie: What do you see as the future for RBQM?
Duncan Hall: RBQM will become central to study planning and execution, driven by commercial imperatives, regulatory authorities, and industry executives. While it is currently more common to apply central monitoring to late-phase studies, we will see it adopted earlier in the study phases where the value is greater. Technology improvements will allow for more efficient deployment and lower costs, making RBQM accessible to studies with smaller budgets.
We are starting to see reports on the environmental impact of clinical research. I expect this will also drive Sponsors to continue pushing for reductions in low-value site monitoring and more patient/device-reported data.
I also think it’s challenging to consider the future of RBQM without considering the role of AI in that future. AI will help with protocol development, risk assessment, data mapping, and interpretation of data, making intelligent recommendations at all clinical trial stages. However, in the near future, human operators will still make the final decisions. The future of RBQM is bright, with improvements in technology, changing mindsets, and increasing regulatory support driving its adoption across all phases of clinical trials.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.