Regulatory changes, including the launch of ICH E6(R3) and Good Clinical Practice (GCP) updates, have highlighted the value of, and need for, risk-based quality management (RBQM) approaches. With benefits including higher quality in clinical trial implementation and lower monitoring costs, the average proportion of clinical trial implementing RBQM is expected to increase to around 80% by 2027.1
So, how has RBQM evolved, what benefits does it offer and what does the future hold?
The History of RBQM
RBQM has been around for more than a decade. Its conceptual foundation was laid by the FDA in 2004 when it set out its Quality by Design (QbD) principles in drug development. Regulators began encouraging RBQM as a specific approach in 2011 and it was more firmly entrenched in guidance in 2016 with the publication of ICH E6 (R2).
Earlier this year ICH E6 (R3) provided greater clarity on proactively designing quality into clinical trials, identifying critical-to-quality issues and adopting risk-proportionate approaches. It also shifted the focus from data integrity to data reliability. Further refinements from regulators are expected in ICH E8 (R1).
This regulatory support, combined with a growing evidence base, is helping to drive a shift within the industry and wider adoption of RBQM approaches.
The Principles
There is no one-size-fits-all approach to RBQM but it does have two main principles – 1) setting clear organisation goals to drive improved quality oversight and 2) ensuring proportionality, effectiveness of actions and mitigations align to the risk profile of the study.
If we consider RBQM throughout the study lifecycle, the start of improving quality begins with a protocol which aims to drive quality outcomes. But as we all know, no protocol can completely eliminate risk or quality concerns for patients. We must accompany improved protocol design with proper risk planning and mitigation to further enhance the quality of the trial.
Different organisations will be at different levels of maturity with initial risk assessment. Research published by the Tufts Center for the Study of Drug Development earlier this year mapped levels of RBQM maturity by company size. It found larger companies were likely to be more mature in their adoption of RBQM.2
Whatever the level of maturity, the goal should remain a tireless push to become more proactive with the monitoring of efficacy and safety data. As we move from the start of the study into execution, the two main principles should continue to remain in view as we start the site monitoring activity.
Moving Away from Source Data Verification
Analysis published in 2014 found just over 1% of EDC data was impacted by 100% source data verification (SDV).3 All reviews resulted in 3.7% of data being corrected or impacted. This meant a huge investment for what appears to be a very modest return on investment (ROI) in terms of corrected data. It also raised the question of whether traditional methods were finding the errors that matter.
Experienced site monitors would argue that the more effective actions driving quality data entry are attributed to better site training on the protocol, assisting sites to understand CRF requirements, providing guidance on query resolutions, and spending more time reviewing source data to look for missing data, adverse events and concomitant medications.
