Risk-Based Monitoring: From the Road Less Traveled to Productivity Superhighway

The latest news on the growing cost of conducting clinical trials is becoming a major concern for company sponsors and trial co-operative groups.Clinical trials cost 60% more today than they did just five years ago, due to the added complexity of what is being studied and the cost to manage and monitor multiple trial sites to enhance recruitment.  And, while late-stage costs have leveled off in the last year, early-stage clinical trials have experienced a triple-digit increase since 2008.

These figures, coupled with growing pressure to accelerate time to market for new therapies, drive home the urgent need to rethink clinical trial management.  Increasingly, trial sponsors and their contract research organization (CRO) partners are turning to risk-based monitoring as the new frontier for clinical trial productivity.

Risk-based monitoring represents a smarter way forward.  It focuses on risk factors with the intent of conducting clinical trials more efficiently and cost effectively, while protecting patient safety, data integrity, and supporting compliance.

The U.S. Food and Drug Administration (FDA) supports the move.  In 2013, it paved the way for a new era of clinical trial management with the release of new guidance on clinical trial oversight.  The FDA called for expanded use of risk-based monitoring - encouraging sponsors to take advantage of electronic systems and focus clinical trial oversight activity on preventing risks to data quality and critical processes to patient safety and trial integrity.

Historically, industry best practices for clinical trial monitoring prescribed 100% source data verification (SDV) with monitors dispatched to visit each investigation site regularly to evaluate data and processes that impact protocol compliance.  Risk-based monitoring, in contrast, focuses on centralized and off-site monitoring with an emphasis on partial (or targeted) SDV.

SDV is arguably the most time-consuming activity for monitors on-site, and a risk based approach enables clinical research associates (CRAs) to focus on more critical compliance activities - including patient informed consent, completion of essential documents, and site compliance with study protocol.

While the core concept of risk-based management is not new, its viability as a reliable and feasible methodology is.  Widespread adoption of trial simulation, planning and trial design systems, and the use of advanced data capture technology (including EDC but extended to cater for multiple data sources) is fundamental to this transition.  With electronic case report forms (CRFs) emerging as a de facto standard and coupled with a real-time analytical platform, trial sponsors and CROs can more easily transform this data into a central repository - that would also contain clinical, safety, molecular, quality, and operational data from multiple sites and studies.  In addition, advanced analytics solutions can now provide study managers with critical predictive insight into trends and triggers, as well as the ability to understand which factors correlate with increased risk.

It is important to note that with risk-based monitoring, the role of the monitor and why we monitor does not change.  But, new technology, including electronic systems and mobile applications, will play an expanded role in helping CRAs execute risk-based monitoring strategies.

Core clinical systems should include activity-based study modeling, true end-to-end clinical data management, clinical trial management systems, safety monitoring systems, and operational analytics to inform study design and tie systems together in a single source of truth.  In addition, innovative mobile apps are emerging that provide CRAs with visibility into real-time trial and site operational data that help them determine, based on critical data and process indicators such as screen failure rates, if they can skip a planned visit or make an unplanned visit - all while on the road.  CRAs can leverage this increased mobility to help them manage the on-site visits they do make to be more efficient and productive, and adapt more quickly to changes.

Despite compelling benefits, trial managers have been apprehensive to become early adopters of risk-based monitoring due to overarching concerns about patient safety and absent guidance.  But, with guidance from the FDA, European Medicine Agency (EMA), Medicines and Healthcare Products Regulatory Agency (MHRA), and echoed industry-group support and technology, sponsors and CROs are starting to embrace and implement risk-based monitoring.

Successfully implementing risk-based monitoring comes down to three factors:

• Up-front risk assessment identifying critical data and study processes.

• Consistent and quality design and application of that risk assessment across the organization - people, partners, processes, and investigator sites – and, across trial workflow, including clinical systems, protocol designs, and trial design.

• The ability to quickly and easily track the critical data and processes identified in the risk assessment.

With established regulatory guidance, industry standards, and more advanced technology, the path of risk-based monitoring will no longer be the road less travelled.  We can expect to see more organizations embrace a risk-based monitoring approach to reduce trial time, cost, and risk, while enhancing data quality and patient safety.

Mukhtar Ahmed is global vice president, life sciences strategy, Oracle Health Sciences.