Risk-Based Quality Management (RBQM) is fast becoming a staple in clinical research, and the community is still learning new ways in which the approach can add value to drug development and sponsor organizations.
From monitoring sustainability metrics to enabling proactive inspection readiness, the model, which was mandated by the International Council for Harmonization (ICH)’s guideline for good clinical practice, E6(R2), in 2019, has a lot to offer.
During a session at the recent RBQM Live event, Dan Beaudry, Senior Vice President of Customer Success at CluePoints, spoke to leading voices about their risk-based experiences, successes, and what they have learned so far.
Evolving utility
As RBQM has moved into primetime, sponsors are increasingly finding new, sometimes unexpected, benefits, explained Amit Gulwadi, Vice President and Head of Transformation at Alexion, Blake Jensen, Quality and Compliance Executive for Adagio, and Galderma’s Head of Clinical Operations, Jessica Jackson.
The original motivation for adopting the approach, said Jackson, had been to improve efficiency and drive down costs in an era where sponsors are increasingly being asked to do more with less.
“When I first came into the industry, we were asked to read 100% of the data,” she explained. “RBQM has allowed Galderma to read more, but with fewer site visits. As a result, it drives trial efficiency and drives down overall costs without compromising safety.”
The benefits have not stopped there, Gulwadi told the session. “One of the key things we have been tracking has been about our commitment to sustainability – the reduced carbon emissions because of fewer site visits. I would not have even thought about that a year ago.”
Inspection readiness
One of the most important ways risk-based approaches can improve processes is by informing inspection readiness, said Jensen, an FDA auditor before joining Adagio.
“This is changing the way we do clinical operations and monitoring. For example, using risk-based approaches in a quality assurance (QA) role was not something I had anticipated before,” he said.
A small biotech with limited compounds in development will stand or fall on the quality of their submissions, he went on. Still, no amount of manual source data verification (SDV) will uncover every potential issue.
“As a QA person looking at audits and reviewing monitoring reports, there are connections and risks that we will always be blind to. Even medical directors who oversee the depths of the trial will not be able to see some of these things,” said Jensen. “When we plug all of the data into the CluePoints tool, we can see all the potential risks that might be under the surface.”
Access to this information can inform cross-function discussions with QA, clinical operations, and development groups, among others. This allows sponsors to anticipate the questions regulators may ask and prepare accordingly. “If an inspector says ‘this looks funny,’ you can explain that you have already had those discussions, and you can provide the answers,” said Jensen, adding that this kind of proactive management provided a “comfort level” that was unobtainable with traditional means. “It gives us that reassurance that if we make this submission, it will not tank the company.”
Building on this theme, Jackson said that risk-based approaches provided companies like hers, which outsources much of its research to CROs, the opportunity to intervene in a timely manner. “There are certain aspects of a trial that we feel confident outsourcing, but we own safety and oversight,” she said, adding that RBQM generated real-time signals that prompt immediate action.
She cited the example of a research site that had quickly recruited 17 patients during a resource-poor period and had not documented any adverse events for eight months. “Because we were running the CluePoints solution, we could see the alerts. That allowed Galderma to step in and take action immediately. We were proactive and could easily document our reviews for an inspector should they ask about this particular site.”
Acquisition evaluation
Gulwadi also explained that Alexion was using CluePoints’ analytical tools to drive the efficiency of acquisition processes.
“When you acquire companies and assets, you don’t know what you are getting,” he said, adding that evaluating the relevant data was traditionally a “very laborious process” that often missed important information.
“The beauty of the algorithms is that they can surface data trends and discrepancies that provide markers on where to focus deeper dives. That has helped us to understand the risks we are inheriting and that data management, or DevOps needs to absorb much faster,” he explained.
As the method continues to evolve, more “unconventional applications” of RBQM technology are bound to come to light, all three agreed.
To learn more about this topic, please listen to the OnDemand recording from RBQM Live, which can be found here.
