Duncan Hall reflects on the state of RBQM after the CBI conference in November
Part 1 - Regulatory Position
This year’s CBI Risk-Based Monitoring event was the seventh year the event has run. TRI has been involved in the planning and sponsorship of the event since the first in 2013 and has seen enormous changes both in the content and the audiences during that time.
The event opened with a very informative regulatory update. This presentation gave details of five regulatory inspections that have been conducted across different agencies, all since the adoption of ICH E6 (R2). Not surprisingly, the findings from the inspections are now including gaps identified against the new quality management processes introduced in R2.
Of the five inspections, three of the sponsors had gone through the process of R2 adoption and compliance and two had not. The two who had not had findings that cited a lack of protocol risk assessment, lack of risk-based monitoring and poor CRO oversight and specificity of duties. Interestingly, the three sponsors who had adopted R2 had their CRO partners present at the inspections. TRI has worked hard this year to communicate the importance of the Sponsor / CRO partnership under R2 and to see sponsors engaging their CRO partners during inspections makes total sense.
We heard anecdotal commentary from one inspector saying that companies who are relying on 100% SDV as a driver for quality are clearly indicating a lack of understanding of what clinical trial quality means. Perhaps these sorts of monitoring plans are more likely to trigger inspections in the future?
The presentation wrapped up with thoughts on the incoming ICH E8 (R1) – a further indication that the regulatory authorities are looking for quality by design, rather than “quality by accident”. We know what’s expected now, and we know what’s coming, so let’s make sure we continue to drive positive change in the industry finally let go of the apron strings of routine monitoring and 100% SDV.
Part 2 – Current State of RBQM
The key ‘take-out’ message from the conference was that RBQM adoption has finally moved from ‘if’ to ‘how’. Presentations and case studies from both sponsors and CROs showed a myriad of approaches and results achieved. The fact that there were so many different approaches to the implementation of RBQM is a clear indication of the huge range of different interpretations of the R2 guidance. I believe that the difference in interpretation is the reason why the industry has not yet achieved 100% adoption. And what the case studies proved, is that we are far from it.
What is more comforting though is that most companies have at least started their implementation. This is backed up by data presented by Omnicomm:
"Of 210 respondents only 18.2% had not started their R2 compliance program and over 44% were either piloting their new processes or were already fully compliant."
The debate of source data verification (SDV) vs. source data review (SDR) and the relative value of both is a common topic of conversation with our customers, and the debate was nicely framed during a presentation by one of the sponsor organizations present. SDR is the process of checking for compliance, and SDV is the process of checking for transcription errors. By differentiating between them, our clinical trials can prioritize SDR of critical data and data deemed to be at risk of non-compliance, and that we can de-prioritize the checking of transcription errors.
A large sponsor who was an early adopter of RBQM presented a very clear breakdown of their end-to-end RBQM process. Breaking the process down that way makes RBQM feel much more achievable. It also clearly defines which function is responsible for each activity, the sequence of activities, and how information flows between them. I can’t stress enough the value of this sort of approach. It means that by the time a study is active and data is subject to ongoing central monitoring, the prior steps in the process have already made clear: the critical factors; the risks to each critical factor; the strategy for identifying, monitoring and managing those risks; and overseeing the ongoing conduct of the clinical trial. The outputs from this sponsor were very impressive. Their case studies clearly identified data quality issues that were unlikely to have been detected through routine site monitoring and SDV.
According to the Omnicomm survey, the top two challenges to the implementation of RBQM are the inability to develop effective processes, and a lack of skilled resources to execute those processes in active trials. These two challenges accounted for more than a third of all responses.
The other industry hot topic to come up in multiple presentations was Quality Tolerance Limits (QTLs). QTLs are a form of key risk indicator (KRI) used at the study level. KRIs are more typically associated with the site or subject level. QTLs require special consideration because the R2 guidance specifically calls for their usage. The guidance also requires specific documentation of any breaches to the determined limits. It is therefore understandable that companies running trials are concerned about creating a documentation burden. They also don’t want to QTLs breeches to be perceived by regulatory authorities as a sign that their clinical is of ‘poor quality’. On the positive side, QTLs can be a very powerful early warning system for systemic issues driving an overall quality trend. If given due consideration, QTLs can be a good signal to the regulatory authorities that you are taking RBQM seriously.
With QTLs we would suggest that you start simple, with one or two QTLs per study to start with and build confidence and capability from there. Once again, the Omnicomm industry survey backed up the significance of this challenge by reporting that only 17.97% of respondents have fully implemented QTLs.
In the next and final part of this three-part blog, I will be looking at some of the expected trends in 2020 and those factors which we feel are likely to be shaping RBQM agendas as we start the New Year.
Part 3 - Predictions for 2020
Reflecting on RBQM in 2019, and not just at the CBI conference, I am struck by how the RBQM conversations I'm having are turning quickly from "why" to "how". In 2020 we'll see a much greater focus on implementation and the 'operationalizing' of RBQM and the rise of innovations like the Integrated Strategic Monitoring Plan to ensure that everything relevant is considered under R2. And we're also expecting more on E8 which will only reinforce the requirement for RBQM in everything we do, It's going to be an interesting year :-)