It was a great conference, but...

Rachel Oakley, VP RBQM Services, reflects on the 4th European CQRM Conference, Feb 2020 Summary It was a great conference, but... There was lots of excellent content, but it’s disappointing that there are still so many conferences where people talk about the “Why?” about RBQM rather than the “How?”  The “Why?” should be obvious for two very simple reasons: 1) the regulatory authorities are mandating it, so you have no choice, and; 2) it’s the obvious and right thing to do. Out next opportunity to help move the conversation on to the “How?” is at the 11th Proactive GCP Compliance conference 16-18 March in Philadelphia where Duncan Hall is presenting how to create an Integrated Strategic Monitoring Plan to deliver fully joined-up RBQM across your trials.

Overview The main theme from the conference was that a good quality culture must be present throughout the whole organization to drive the changes required for RBQM. Don’t make it too complex by writing lots of additional SOPs. Weaving RBQM into existing SOPs will be far more successful. There was an interesting discussion on the first day around the milestone of FPFV driving a lot of the start-up work. This puts pressure on speed, cost, and quality, to the detriment of the trial. There seemed to be an understanding in the room that companies should be more realistic around this milestone and give themselves more time to be properly ready to start a study. However, there was also a recognition that sometimes it’s driven by the stakeholders and you have no choice but to meet those timelines. Finally, and most importantly, as a company you may have good processes or technology in place, but if the people have not been engaged in the changes, or not trained properly, RBQM cannot and will not be successful.

Proactive Risk Management Critical thinking is the essence of RBQM, underpinning the culture that supports and defines it.

Risks should be managed in clinical trials, both for subject protection and reliability of trial results, but importantly they should be managed proactively rather than reactively. By keeping it simple and articulating the risks, the focus can be on preventing what may happen rather than fixing what already has. One size does not fit all, and each risk must be specific to individual studies. However, leveraging analytics and understanding what has happened in previous studies, audits, and inspections, can be a great help in developing a proactive strategy. For this to be successful, leadership support and a credible QA group are all vital to implementing RBQM. By deciding on a QRM framework for your company, inspectors can see this process documented throughout the course of the study. This means they can watch it grow and evolve as your trials do. Implementing the best strategy for your organization, using your resources where they are most valuable, (low risk = less time, high risk = more time) and effective change management are all critical for success. To achieve Proactive Risk Management, identify the key decision-makers, ensure a quality culture and understand what risk is.

MHRA Update One of the ‘Hot Topics’ discussed was where and how you preserve data. The big question is about validating the cloud – is it secure enough for the type of data you are storing? Changes in technology are impacting on how the MHRA review data for inspections. This includes the time they spend on their investigations as well as often conducting the first day of an inspection remotely in their own office. This allows them to make sure they know what systems are being used for the trials and how to gain access to them. They are also trying to support innovation in clinical research, for example, looking at different trial designs such as bucket trials, adaptive trials, advanced therapy trials, personalized medicine etc. The MHRA are having to look more at data integrity items, inspecting providers of data systems such as ePRO, IRT, EDC, independently and not just part of a trial audit. They’re also keeping a close eye on things such as validation and change controls, as well as reviewing audit trail data and metadata.

"Risk assessments are more critical now than they have ever been before, including their ongoing management – this will be an area of focus for the MHRA."

It’s important to get the design of the trial right as early as possible, and the MHRA has set up a support office to help sponsors with this. They have also been working with the NHS on EHRs to ensure they are fit for purpose, including clinical research. One of the questions asked was “Is there a go-to document the MHRA looks for regarding risk?” The short answer was there’s not a specific document, but they are looking to see that a risk assessment was performed and that the trial risks were identified, documented, and mitigated. They also want to see that the Risk Assessment is a living document that is reviewed in an appropriate timeframe. For example, reviewing at suitable points i.e. protocol amendment; or if it’s an adaptive trial, at the time an adaption is made. It’s important to the MHRA that they can see how the Sponsor has followed this approach. What is the impact of E6(R2) and E8(R1)? The key message of this presentation was to emphasize the role of achieving quality through good design.

Questions were raised about getting your organization to embrace these changes and ensuring compliance. Companies were encouraged to keep clinical research simple, valuable and patient-centric. Approaches are needed for optimizing trial quality which promotes the reliability, efficacy, and patient focus of clinical trials. This involves identifying the factors that are critical to the quality of a clinical trial at the design stage. Planning trial conduct proportionate to the risk of these quality factors, protecting human subjects, and ensuring the reliability of trial results is also very important. This modernization of ICH E8 is the first step toward the GCP renovation initiated in 2017.

Good protocol design is the key to achieving compliance and sponsors were encouraged to invest in ‘mock’ inspections to ensure staff are ready. Workshops with key stakeholders to engage them in study design were also recommended.

Conclusion It was a useful and interesting conference. It’s always helpful to hear the views of the regulatory bodies to ensure we’re on the right track with RBQM. Having been to this conference I’m more convinced than ever that we are. I’m also convinced that there are lots of companies out there that need help on their RBQM journey, whether they’re right at the start or wanting to improve their effectiveness and efficiency. Our purpose in life is to make RBQM simple and it’s an honor and a privilege to be able to help so many great people make a difference with their very important work. Rachel Oakley VP RBQM Services