James Streeter, Senior Director, Oracle Health Sciences01.29.15
Clinical trials cost 60% more today than they did just five years ago. This is due to the added complexity of new studies and the cost to manage and monitor multiple trial sites that enhance recruitment. And, while late-stage costs have leveled off in the last few years, early-stage clinical trials have experienced a triple-digit increase since 2008.
There is no question that driving down the cost of clinical trials, while grappling with intense pressure to accelerate time-to-market for new therapies, presents a formidable challenge. It is also abundantly clear that a viable solution will require a fundamental rethinking of the way clinical trials are managed.
Increasingly, trial sponsors and their contract research organization (CRO) partners are turning to risk-based monitoring as the new frontier for clinical trial productivity and efficiency. While the core concept is not new, its emergence as a viable, reliable and feasible methodology is giving health sciences organizations reason for careful consideration and, in some instances, outright optimism.
Just as with any major initiative, success is not assured. It requires careful planning and a cultural shift, as well as an infrastructure that can support new requirements, and ultimately, reduce risk.
A Better Way Forward
Risk-based monitoring represents a smarter path forward. That is, it is a holistic, dynamic approach founded on trial risk factors. This approach enables researchers to conduct clinical trials more efficiently and more cost effectively, while ensuring patient safety, data integrity and compliance.
Historically, industry clinical trial best practices for monitoring required 100% source data verification (SDV), with monitors dispatched to visit each investigation site for regular evaluation of data and processes that impact protocol compliance. This was a costly proposition and an approach that was not guaranteed to produce superior results. In contrast, risk-based monitoring focuses on centralized and off-site monitoring and employs partial, or targeted SDV.
Due to overarching concerns about patient safety, trial managers have been apprehensive to become early adopters of risk-based monitoring, despite attractive cost and efficiency benefits. However, in 2013, the U.S. Food and Drug Administration (FDA) released new guidance on clinical trial oversight and this began to pave the way for a new era of clinical trial management.
The FDA called for expanded use of risk-based monitoring. This encouraged sponsors to use electronic systems and focus clinical trial oversight on preventing risks to data quality and the critical processes that ensure patient safety and trial integrity.
We’ve also seen new guidance from the European Medicines Agency (EMA) and Medicines and Healthcare Products Regulatory Agency (MHRA), as well as widespread industry-group support and tools, such as TransCelerate’s Risk Assessment Categorization Tool. All of these encourage sponsors and CROs to actively implement risk-based monitoring initiatives.
Time to Be Strategic
With risk-based monitoring, the fundamental role of the monitor doesn’t change, but there is significant opportunity for added value. SDV is arguably the most time consuming activity for monitors on-site. A risk-based approach enables these clinical research associates (CRAs) to focus on more critical compliance activities, such as: patient informed consent; completion of essential documents; site compliance with study protocol; and Good Clinical Practice (GCP) principles.
Achieving this transformation, however, requires careful focus that is not just on the SDV, KPIs and KRIs, but holistically looks at how you plan, design, execute, analyze, and report on implementing risk-based monitoring for a trial.
Planning
Planning encompasses initial risk assessment, including identification and prioritization of risks for the specific product. Organizations also require the flexibility to adapt strategies that meet the needs of individual trials and program requirements for risk-based monitoring. These requirements may vary by development phase, therapeutic areas, previous trial experience, risk experience across the industry, and many other areas.
Design
Design involves defining parameters/key risk indicators needed for monitoring the trial under a risk-based monitoring approach. It involves quality design and workflow creation, as well as understanding the criteria, such as defining the risk areas of how sites will follow the inclusion/exclusion criteria. The importance of the planning and design phases cannot be overstated, as they form the foundation for a successful, risk-based monitoring initiative. Allotting insufficient time and resources for these initial phases is a common pitfall.
Execution
Execution requires consistent application of risk assessment factors—people, partners, processes and investigator sites—across the organization and trial workflow—clinical systems, protocol designs and trial design. This phase puts planning and design into action and requires significant data integration capabilities.
Analysis
One must ensure the capacity for quick and easy tracking of the critical parameters and processes identified in the risk assessment and for transforming this information into immediately actionable insight. For example, identifying trends of sites not following inclusion/exclusion criteria.
Report
The report closes the loop in terms of regulatory compliance with the ability to rapidly, accurately and automatically document adherence and validity of executing the risk-based monitoring approach identified during the planning/design.
Getting Connected
Technology and access to data—as well as insight into processes—play a critical role in enabling successful risk-based monitoring strategies. Widespread adoption of advanced data capture technology—electronic data capture, but extended to accommodate multiple data sources like patient devices and electronic medical records—is fundamental to enabling approaches to risk-based monitoring.
In addition, access to all the data collected across all the systems, studies and sites with advanced analytics solutions provide study managers with critical, predictive insight into trends and triggers. These advanced tools also provide study managers with the ability to understand which factors correlate with increased risk at a particular site, in a particular study, or even systemically, as the foundation for a best-practice moving forward.
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, centralized source.
To be truly successful, however, these systems need to bring site monitors (CRA) into the picture, giving them anywhere, anytime access to real-time trial data so that they can make faster and more informed decisions about potential risk and corrective actions.
Fortunately, new innovative mobile apps developed solely for this purpose, now provide CRAs with real-time trial and site operational data. These new apps, using critical data and process indicators from core systems, such as screen failure rates, help CRAs determine if they can skip a planned visit or make an unplanned visit, all while on the road. CRAs can then leverage this increased mobility to adapt more quickly to changes and make the on-site visits they do conduct more efficient and productive. The result? Better risk management, higher-quality data and processes, and enhanced patient safety—all at lower cost and with less manual effort.
The New Year brings new potential to drive greater efficiency throughout the clinical development process. Risk-based monitoring is poised to play a pivotal role in this important industry priority. With established regulatory guidance, evolving best practices and more advanced technology, the path of risk-based monitoring is no longer perilous.
References
James Streeter is Senior Director of Life Sciences Product Strategy within Oracle’s Health Sciences Global Business Unit. He previously held leadership roles at PPD as the Global Head of Global Clinical Technical Operations and EDC, and in IT as Global Head of Systems Development, Business Operations Teams, and eClinical Strategy and Innovation.
There is no question that driving down the cost of clinical trials, while grappling with intense pressure to accelerate time-to-market for new therapies, presents a formidable challenge. It is also abundantly clear that a viable solution will require a fundamental rethinking of the way clinical trials are managed.
Increasingly, trial sponsors and their contract research organization (CRO) partners are turning to risk-based monitoring as the new frontier for clinical trial productivity and efficiency. While the core concept is not new, its emergence as a viable, reliable and feasible methodology is giving health sciences organizations reason for careful consideration and, in some instances, outright optimism.
Just as with any major initiative, success is not assured. It requires careful planning and a cultural shift, as well as an infrastructure that can support new requirements, and ultimately, reduce risk.
A Better Way Forward
Risk-based monitoring represents a smarter path forward. That is, it is a holistic, dynamic approach founded on trial risk factors. This approach enables researchers to conduct clinical trials more efficiently and more cost effectively, while ensuring patient safety, data integrity and compliance.
Historically, industry clinical trial best practices for monitoring required 100% source data verification (SDV), with monitors dispatched to visit each investigation site for regular evaluation of data and processes that impact protocol compliance. This was a costly proposition and an approach that was not guaranteed to produce superior results. In contrast, risk-based monitoring focuses on centralized and off-site monitoring and employs partial, or targeted SDV.
Due to overarching concerns about patient safety, trial managers have been apprehensive to become early adopters of risk-based monitoring, despite attractive cost and efficiency benefits. However, in 2013, the U.S. Food and Drug Administration (FDA) released new guidance on clinical trial oversight and this began to pave the way for a new era of clinical trial management.
The FDA called for expanded use of risk-based monitoring. This encouraged sponsors to use electronic systems and focus clinical trial oversight on preventing risks to data quality and the critical processes that ensure patient safety and trial integrity.
We’ve also seen new guidance from the European Medicines Agency (EMA) and Medicines and Healthcare Products Regulatory Agency (MHRA), as well as widespread industry-group support and tools, such as TransCelerate’s Risk Assessment Categorization Tool. All of these encourage sponsors and CROs to actively implement risk-based monitoring initiatives.
Time to Be Strategic
With risk-based monitoring, the fundamental role of the monitor doesn’t change, but there is significant opportunity for added value. SDV is arguably the most time consuming activity for monitors on-site. A risk-based approach enables these clinical research associates (CRAs) to focus on more critical compliance activities, such as: patient informed consent; completion of essential documents; site compliance with study protocol; and Good Clinical Practice (GCP) principles.
Achieving this transformation, however, requires careful focus that is not just on the SDV, KPIs and KRIs, but holistically looks at how you plan, design, execute, analyze, and report on implementing risk-based monitoring for a trial.
Planning
Planning encompasses initial risk assessment, including identification and prioritization of risks for the specific product. Organizations also require the flexibility to adapt strategies that meet the needs of individual trials and program requirements for risk-based monitoring. These requirements may vary by development phase, therapeutic areas, previous trial experience, risk experience across the industry, and many other areas.
Design
Design involves defining parameters/key risk indicators needed for monitoring the trial under a risk-based monitoring approach. It involves quality design and workflow creation, as well as understanding the criteria, such as defining the risk areas of how sites will follow the inclusion/exclusion criteria. The importance of the planning and design phases cannot be overstated, as they form the foundation for a successful, risk-based monitoring initiative. Allotting insufficient time and resources for these initial phases is a common pitfall.
Execution
Execution requires consistent application of risk assessment factors—people, partners, processes and investigator sites—across the organization and trial workflow—clinical systems, protocol designs and trial design. This phase puts planning and design into action and requires significant data integration capabilities.
Analysis
One must ensure the capacity for quick and easy tracking of the critical parameters and processes identified in the risk assessment and for transforming this information into immediately actionable insight. For example, identifying trends of sites not following inclusion/exclusion criteria.
Report
The report closes the loop in terms of regulatory compliance with the ability to rapidly, accurately and automatically document adherence and validity of executing the risk-based monitoring approach identified during the planning/design.
Getting Connected
Technology and access to data—as well as insight into processes—play a critical role in enabling successful risk-based monitoring strategies. Widespread adoption of advanced data capture technology—electronic data capture, but extended to accommodate multiple data sources like patient devices and electronic medical records—is fundamental to enabling approaches to risk-based monitoring.
In addition, access to all the data collected across all the systems, studies and sites with advanced analytics solutions provide study managers with critical, predictive insight into trends and triggers. These advanced tools also provide study managers with the ability to understand which factors correlate with increased risk at a particular site, in a particular study, or even systemically, as the foundation for a best-practice moving forward.
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, centralized source.
To be truly successful, however, these systems need to bring site monitors (CRA) into the picture, giving them anywhere, anytime access to real-time trial data so that they can make faster and more informed decisions about potential risk and corrective actions.
Fortunately, new innovative mobile apps developed solely for this purpose, now provide CRAs with real-time trial and site operational data. These new apps, using critical data and process indicators from core systems, such as screen failure rates, help CRAs determine if they can skip a planned visit or make an unplanned visit, all while on the road. CRAs can then leverage this increased mobility to adapt more quickly to changes and make the on-site visits they do conduct more efficient and productive. The result? Better risk management, higher-quality data and processes, and enhanced patient safety—all at lower cost and with less manual effort.
The New Year brings new potential to drive greater efficiency throughout the clinical development process. Risk-based monitoring is poised to play a pivotal role in this important industry priority. With established regulatory guidance, evolving best practices and more advanced technology, the path of risk-based monitoring is no longer perilous.
References
- “Clinical Development and Trial Operations,” Cutting Edge Information, 2013. http://www.cuttingedgeinfo.com/research/clinical-development/trial-operations/
James Streeter is Senior Director of Life Sciences Product Strategy within Oracle’s Health Sciences Global Business Unit. He previously held leadership roles at PPD as the Global Head of Global Clinical Technical Operations and EDC, and in IT as Global Head of Systems Development, Business Operations Teams, and eClinical Strategy and Innovation.