Risk-based monitoring (RBM) has long been touted as a way to reduce clinical trial risk and improve data quality. Under ICH E6 guidelines, even if relying on CROs for all trial activities, sponsors are ultimately responsible for quality, safety and efficacy. However, most risk monitoring tools and processes lack the transparency and integration clinical trial sponsors and CROs need to comply with the guidance, proactively manage risks and keep their trials on track and on budget.
In order to drive real-time cost and quality benefits, sponsors and CROs should focus on quality by design throughout the clinical trial and adopt a Risk Based Quality Management (RBQM) approach. This calls for a significant shift from today’s resource-intensive and reactionary mindset, to one that’s more proactive and data-driven.
An effective RBQM strategy requires technology that can provide an integrated view of trial data from multiple sources using risk and performance indicators to drive real-time decision making. With system generated alerts to notify study teams of risk signals at a portfolio, study, country, or site level, study teams can both proactively and efficiently assign action items to the appropriate stakeholders for proactive mitigation, empowering sponsors and CROs to identify and address emerging issues before they become problems that endanger the safety, quality, compliance, or performance of their studies.
The Promise of RBQM
RBQM promises to dramatically reduce site performance and data quality issues by enabling sponsors and CROs to:
⋅Focus on critical data for more focused protocols with lower patient burden
⋅Use data analytics to focus oversight on outlier issues and risk signals
⋅Operationalize and automate risk plans with predictive analytics and prescriptive alerts
Organizations who embrace RBQM will ultimately be able to build on their experience and use benchmarking data to model which interventions improve performance, and incorporate learnings into subsequent risk plans, to increase machine learning and decrease manual assessments. As a result, companies can leverage this insight to model resource allocation, and benefit from prescribed threshold suggestions based on previous outcomes, such as working with a new site, within specific countries, protocol complexity, or indication experience levels.
Getting Started: 4 Key Steps
To make the transition to RBQM, sponsors and CROs need to create a roadmap for transformation, with key milestones for adapting the people, processes, and technologies involved in their risk management strategies (Figure 1). Critical steps include:
1. Implement and document collaborative risk assessment processes with supporting SOPs and configurable responsibility matrices.
The 2016 ICH E6 (R2) Addendum to Good Clinical Practice clearly defines the trial sponsors responsibilities for implementing the processes and technology required to oversee patient safety, data integrity, and compliance with quality management processes across all outsourced service providers, including sub-contracted vendors. This requires sponsors to invest in the resources, technology, and process changes required to implement proactive oversight practices across trial data, geographic regions, investigative sites and service providers using a flexible but consistent process that is data driven, and fully auditable from risk identification through root cause analysis, risk mitigation and resulting outcomes. Success will be contingent upon close collaboration and communication with stakeholders to ensure a single source of truth is being used by all parties to both manage and oversee trial activities.
2. Don’t create KRI’s from scratch.
Begin with Industry Best Practices & Consortiums. While every trial faces a unique set of risks presented by trial complexity, endpoints, site, indication, and country experience, organizations such as TransCelerate, Metrics Champion Consortium, and Clinical Trials Transformation Initiative (CTTI) have published proven risk assessment tools, related KRIs, proven frameworks and other materials that are invaluable resources for organizations looking to implement a quality-by-design approach. Regulatory guidances on risk-based monitoring and implementing quality metrics for study and vendor oversight are also publicly available. Starting with proven standards, organizations can leverage these learnings into the development of reliable KRIs focused on specific risks related to study indications, protocol design, or compound safety profiles.
3. Choose the right technology platform.
An effective RBQM solution will provide the necessary integration, transparency, and analytics capabilities to drive real-time risk identification and mitigation. However, many organizations cite the number of data sources required to centralize risk monitoring as a challenge. Before choosing a system, sponsors and CROs should verify that it has the ability to integrate and aggregate data in real-time, and doesn’t require an internal means of serving up the data to their RBM system. Otherwise, they will be left with a data visualization tool that doesn’t have the right data, or has it too late to be actionable.
4. Retrain staff and fill talent gaps.
Monitors and site staff will need training on how to operate in an RBQM environment, including how risk indicators are defined and configured and the expected mitigation responses when risks do occur. Data and analytics play an important role in supporting these programs, so companies may also benefit from ensuring staff has the data analytics and technical expertise required to navigate the data-driven trial environment.
RBQM: The Time is Now
When implemented effectively, an RBQM approach helps sponsors and CROs mitigate risks before they become costly problems, and ensures the best quality data are captured consistently throughout the trial lifecycle. By following the best practices described above, all organization have the potential to continuously identify study performance improvements and achieve significant cost savings throughout their clinical trials.
For more information on improving clinical trial performance and data quality with real-time management, read ‘Moving Beyond Risk-based Monitoring.’
Brion Regan is the Director of Product Management for Trial Oversight at ERT.