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The Absence of Errors That Matter: The Value of RBM in QbD

Halloran Consulting Group, in collaboration with Boston Scientific (BSC), recently hosted a Clinical Operations Breakfast – a community of clinical operations professionals that meet monthly over a virtual breakfast to share common challenges and solutions  – to discuss “The New Risk-Based Monitoring: The Path Ahead and Ideas for Implementation” for the conduct of clinical studies. The COVID-19 pandemic has forced the hands of sponsors to begin immediate incorporation of risk-based monitoring (RBM) into clinical studies and a “new normal” is on the horizon. The BSC team shared their journey to implementation and how companies of all sizes can take steps to accelerate the use of RBM into their studies. With lively engagement from participants, the ultimate question to be answered is “How much data do you need to see to be comfortable that the study data is accurate?” 

Why RBM and Quality by Design Matters (QbD)

Quality by Design in clinical trials is defined as the absence of errors that matter. The use of RBM, specifically, in clinical trials allows operations teams to focus their efforts on monitoring the activities of the study that are crucial to the study outcomes. In today’s clinical research world, trial data is entered in real-time. Gone are the days of sponsors getting a first look at data from an annual report after manual entry from paper Case Report Forms. With the implementation of Electronic Data Capture (EDC), data collected at sites is quickly available for centralized aggregate data review. This tactic, along with focused source data review, has been shown to produce higher quality data at a more efficient cost, but the industry has been slow to redefine monitoring from a traditional 100% SDV process to a more risk-based approach.

Boston Scientific Journey

About three years ago, the team at BSC began to examine the traditional model for monitoring and asked how they could evolve to a new model using risk-based processes. The organization, like many biotech companies, was shifting focus in their trials toward a culture of quality by design, which influenced the implementation of RBM. Much like in today’s COVID world, the question was “what is the least amount of data we need to advance the trial while maintaining patient safety and data integrity?”

BSC built a team composed of experienced operations professionals to utilize existing technology in trial conduct. The initial decision to shift from the comfort zone of traditional monitoring to RBM, and the subsequent commitment to stick with it and “lean in” was the biggest hurdle to overcome, but it was the buy-in from top down that drove successful implementation.

Where to Start?

Not all companies are the size of nor have the resources to create an entire department dedicated to the implementation of RBM that a larger company like BSC has. Many of the attendees at the breakfast asked how to start – and this is a common question we hear in the community – especially when so many companies are already moving at full speed with limited resources. There isn’t time to pause to redesign operational structure, so companies are required to adopt changes while in motion. COVID has created an opportunity to accelerate strictly out of need. Whether the motive is born strictly out of need or planning was already in the works, advice for implementation of RBM was much the same:


Implementation of RBM is not without challenges. As it takes a shift in mindset within companies, it also requires a broader shift in the thinking across the industry. Standard practices are comfortable and to some, RBM feels like giving up control of data so engaging across functional areas has been slow.  Likewise, ensuring vendors are aligned can also be a challenge. Setting clear ownership and expectations up front can help alleviate some of the concerns. For example, getting input from all stakeholders to inform the risk assessment is critical. Using the RACT as a measurement tool to then inform study plans across all functional areas will provide all stakeholders documented details of the work to be done, how it will be measured, and the prescribed escalation.

Another challenge for sponsors is determining how to measure and document SDR since it is less clear cut than traditional 1:1 SDV. Documentation of SDV that is focused on a smaller number of data points related to safety and/or endpoints can be easily captured as it has been with traditional monitoring.  However, the question remains how to most efficiently capture source data review to avoid additional inefficiencies like documenting every page that has been reviewed into CTMS, for example.

Concerns exist about implementation of RBM at ex-US sites considering GDPR and privacy concerns. Overall, there needs to be further engagement across the industry in various regions with prohibitive guidelines to determine how to move forward. COVID has allowed for some relaxation of guidelines like remote review of EMR in some countries but it remains to be seen if these will be long-lasting changes.

Finally, training particularly at the monitor level needs to be revised. Additional competencies of critical thinking and data analysis to evaluate and assess quality need to become a part of job descriptions for monitors. However, ensuring employees that their jobs are not becoming obsolete and providing robust training and onboarding will be key to maintaining staffing and preventing turnover.

The Value of RBM

Where will companies find the value of implementing robust risk-based monitoring? The change in processes related to RBM and utilization of technology can impact time, quality, and cost. In the long-term, those impacts can improve patient outcomes, bring new treatments to patients faster, and ease burden on study sites.

RBM is an evolving process, sped along by the need to quickly adapt due to COVID. Prior to the pandemic, less than half of the participants in the breakfast had implemented RBM strategies at all while another third were only in the planning implementation. However, during COVID, most if not all had begun using technologies such as file sharing, video conferencing, and access to EMR to facilitate monitoring remotely. COVID has amplified the need for the shift and change is beginning. The opportunity to adapt and accelerate change, step-by-step, is now to ensure the industry keeps moving forward.