By Deborah Borfitz

December 1, 2021 | Most pharmaceutical companies today have a dedicated team for risk-based quality management (RBQM) whose job it is to imagine the many ways clinical trials could go wrong to prevent their failure. Gone are the days when averting risk was largely an exercise in source data verification based on the perceived difficulty in study execution, says Marcin Makowski, M.D., Ph.D., head of centralized monitoring and data analytics at GlaxoSmithKline (GSK).

The required skillset has evolved along with the expanding breadth of the job, he says, from a role requiring expertise in facilitating projects to one demanding a deep understanding of a therapeutic area and drug development in general. Perhaps most importantly, RBQM needs people who can guide study teams in the creation of a “post-mortem analysis” before trials begin.

Makowski has a decade of experience in the creation and development of RBQM/centralized monitoring teams, first with AstraZeneca and more recently with GSK. He will be sharing some of his personal best practices for recruiting and nurturing top-notch teams during a presentation at the 2022 Summit for Clinical Ops Executives (SCOPE).

One of the major challenges in the field is that the impact of a poor-quality clinical trial on overall study results is vastly under-appreciated, says Makowski. Deficits in quality may produce findings that are false or dubious. “Either we have a result that no one believes in or… we can presume is not the best reflection of the scientific question that was asked.”

In his mind, a good study has four crucial components—the “right population, right exposure to treatment, right collecting of the data, and no bias”—and the biggest problems are with the populations and completeness of the data. Enrollees frequently do not reflect the intentions of trial designers for reasons that are not yet fully understood, he says. The data completeness issue has started to work itself out because of growing awareness of the impact on study results.

‘Spark In The Eye’

It has become clear in recent years that it will take some time for RBQM to be part of the DNA of organizations, says Makowski, noting that some companies who tried embedding it into the normal ways of working have since switched to having dedicated roles. RBQM teams are sometimes part of, and other times separate from, the data monitoring group or clinical operations team.

Regardless of where it resides, the responsibilities of the RBQM role are ideally suited for individuals who find pleasure in exploring scientific information, he continues. He looks for that “spark in the eye” in the people he employs when they complete an assigned research task as part of the recruitment process.

Makowski’s rationale for these “assignments” (e.g., necessity of blinded independent review of outcomes for a fictitious study) is that clinical trials are scientific experiments and RBQM team members should therefore find science appealing—and excitedly return from a multi-day literature search to share their findings and position on the question at hand. The presentation itself is less important than the job candidate’s demonstrated ability to digest publicly available scientific information to gain an opinion on the subject, he says.

To help RBQM team members maintain the passion they first brought to the job, Makowski’s team hosts an ongoing Science Corner series involving role-playing exercises with employees in lieu of lectures. “I am trying to ensure that we devote a significant amount of time in exploring and discussing a scientific topic that has absolutely no relation to our daily job,” he explains.

For example, one recent Science Corner meeting began with a 20-minute presentation on one of the world’s most controversial drug approvals. Employees then were split into two groups, one getting materials containing evidence in support of the approval and the other evidence against it. They then strategized, prepared their arguments, and formally debated one another.

“We were discussing scientific data, but it was fun, and we had a lot of laughs,” says Makowski. And that was the point of the exercise—engagement.

During another Science Corner meeting, Makowski had employees perform in pairs as participants in “the simplest trial ever” that he designed for the exercise. The experiment asked whether glasses would help short-sighted people see and the goal was to enact an error in study execution that would produce the wrong result.

One of the competing pairs opted to wear contact lenses, to negate the effects of the corrective lenses. Another pair withdrew their consent, while a third duo inched closer to the eye chart to improve their comparative naked-eye vision. This was repeated six or seven times over the course of an hour, each time followed by an analysis of how their chosen strategy led to the erroneous conclusion that the glasses were unhelpful.

The lesson here was that introducing too many errors in execution can foil even the most well-designed trial, Makowski says. “The quality of a trial,” he emphasizes, “is not just in the tasks.”

Editor’s Note: The opinions expressed in this article are those of Marcin Makowski and not GSK.