Transitioning to risk-based monitoring: opportunities and challenges
By Crystal Stone and Amanda Coogan, risk-based monitoring product specialists at Remarque Systems Inc.
For decades, the pharmaceutical industry has relied on a time- and resource-intensive strategy of placing big bets on a small number of molecules with the hope of turning them into blockbuster drugs. However, as the R&D landscape changes, sponsors and contract research organizations (CROs) are under increasing pressure to move drug candidates safely, quickly, and ever more intelligently through clinical trials.
Adoption of a risk-based monitoring (RBM) approach can help enhance the safety, quality, and efficiency of clinical studies while simultaneously supporting compliance. As the FDA encourages drug developers to integrate digital technologies into the development process, biopharmaceutical companies are increasingly considering automated clinical trial management solutions that incorporate RBM.
RBM is gaining momentum
RBM has been a topic of discussion among the clinical research community since the FDA published its industry guidance “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring” in August 2014. However, implementation has been a challenge and adoption has been slow. More recently, there have been a number of factors accelerating the trend toward RBM:
Regulatory environment. Regulatory focus on RBM has intensified with the update to the ICH Guidelines for Good Clinical Practice and the FDA’s April 2019 draft guidance “A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers.” In fact, RBM is becoming the standard for clinical monitoring.
Digitization. An industry-wide emphasis on modernizing and improving the efficiency of clinical trials—from recruitment to data collection and protocol adherence—is driving the digitization of the entire development process.
Data volume. The trend toward precision medicine and biomarker-guided drug development has contributed toward an increase in the volume and complexity of data generated by clinical trials. Nearly 80 percent of data scientist time is spent collecting, cleaning, and organizing data sets, leaving limited time for data analysis and creating a demand for automated solutions.1
Data quality. Exclusive of investigator fees, clinical monitoring is the largest driver of clinical trial costs, accounting for an estimated 30 percent of all expenses and over 60 percent of labor costs.2 However, studies have shown that these expenditures might be disproportionate to returns in terms of data quality.3
Advantages of RBM technology
RBM offers a dynamic approach to clinical trial monitoring and risk management. Beyond offering a way to view risks, a comprehensive RBM solution provides insight into what the data means for the clinical trial and offers actionable steps that make optimal use of that data, all with an audit trail.
Comprehensive implementation of RBM has the potential to bring a number of clear, measurable benefits:
Automation. More advanced RBM software may utilize machine learning to alert decision-makers about potential risks which were not pre-identified during trial set-up. These technologies analyze prospective data collected during the trial on an ongoing basis to find patterns and anomalies.
Improved patient safety and data quality. RBM technology can track trend information and make actionable data readily available to sponsors and CROs so they can both take corrective action and take steps to minimize these issues going forward, which can improve both patient safety and data quality.
Reduction in on-site monitoring. By determining when it makes sense for monitors to perform site visits based on study-specific risk thresholds and site performance, RBM analytics can help reduce unnecessary on-site monitoring.
Efficiency. RBM can help shorten the timelines for evaluating study data. Data cleaning at the end of a study can be time-consuming (typically greater than three months), and each day of delay can be costly. With RBM technology, data is evaluated on an ongoing basis, which helps minimize the time from the end of the study to the reporting of study results.
Compliance. Regulators are seeking more rigorous assurances of patient safety and data quality. With a robust RBM technology, assurance, traceability, and audit should be built in, enabling drug developers to meet current and emerging regulatory requirements.
Overcoming three challenges of transitioning to RBM
RBM technology can help sponsors and CROs implement comprehensive monitoring strategies from a single platform with automated workflows and advanced analytic capabilities. Especially as RBM software solutions become more sophisticated, navigating the transition can be complex. Understanding some of the key challenges associated with adopting an RBM approach can help drug developers make the shift a smooth one:
Challenge 1: Resistance to change
RBM represents a paradigm shift from traditional monitoring, and drug developers may feel cautious of or resistant to this change. This resistance may be due in part to uncertainty about how the FDA will respond to the use of such new techniques. However, sponsors and CROs should also consider how regulatory agencies might respond if RBM modifications are not made. For companies that do not feel comfortable making the shift to RBM, it may be useful to evaluate the factors underlying that hesitation and to determine how to address it.
Even for companies that are ready to transition to RBM, the change can be daunting. The move toward an RBM approach requires change management related to people, process, and technology. Commitment at the leadership level, along with staff training and a clear understanding of each team member’s roles and responsibilities, helps ensure that RBM is incorporated into the DNA of both the company and the clinical trial.
Challenge 2: Differentiating between the RBM technologies available
While a plethora of RBM technologies exist, their features vary and many fall short of delivering the full benefits of RBM. Some RBM technologies only look at risk in isolation, without context or analysis. Others may be limited by their reliance on retrospective data, missing the critical capability to draw insight from emerging issues or placing undue emphasis on irrelevant historical information. An incomplete approach to identifying, managing, and analyzing risk introduces complexity and cost without adding benefit.
In addition, a system that fails to fully assess risk could also introduce a new risk: a false sense of security. Sponsors and CROs may mistakenly believe that they are utilizing RBM, without fully benefiting from all that RBM can offer.
A comprehensive RBM technology approaches risk from all angles—operational, safety, and quality—and includes:
• Risk identification and assessment. The system should allow users to identify and log critical data and processes relevant to the study. It should also enable users to assess and characterize risk both at the start and throughout the course of the study.
• Risk control and mitigation. For each of the risks identified, the RBM technology should have the ability to control and mitigate the risk through a variety of risk management strategies, which may be automated or manual. For example, the software should be able to issue alerts when risks approached predefined thresholds and when safety or data quality is at risk or compromised. Rather than sending clinical monitors to sites at regular intervals, on-site visits can be scheduled only when the RBM technology signals that such visits are warranted.
• Risk communication and action. The RBM technology should allow for streamlined, centralized review of the risks detected by offering statistical models, intuitive data visualization, and the ability to drill down into the data (e.g., by geography, site, patient or type). The software should also enable users to respond to emerging risks through built-in workflows and ticketing functionality.
• Risk review and updating. Finally, the RBM software should allow for regular and ongoing review and modification of risks. This helps sponsors and CROs ensure that risk management activities remain effective and take into account emerging knowledge and experience.
RBM technology that delivers all of these capabilities can truly empower drug developers to conduct trial monitoring more efficiently, while also improving patient safety and data quality.
Challenge 3: Uncertainty about implementation
As clinical trials become more complex, RBM technologies have also become more sophisticated. Unlocking the full value of RBM technology requires proactive planning, thoughtful implementation, and ongoing strategic execution following deployment.
The process of implementation involves requirements gathering, planning, and testing and should cover five areas:
• Project scope. The scope should be aligned with the needs of the end user(s) and should include clear definitions of roles and responsibilities. Most sponsors benefit from starting with a pilot of the technology, which allows them to familiarize themselves with the implementation process, test the system, and validate internal processes on a small scale.
• SOP/plan impact. This involves review of existing procedures and plans, and updating them or creating new processes if necessary. This is also an opportunity to document how issues identified by the system will be escalated internally.
• Communication. How will the sponsor communicate with both the technology vendor and the end user(s)?
• User acceptance testing (UAT) plan. This is an area many sponsors overlook. UAT should be performed at both the system level and the study-specific level.
• Oversight plan. This involves outlining not only how success and value will be measured, but also how these metrics will be communicated to all stakeholders.
Making the switch to RBM
The transition to RBM requires proactive planning and alignment of the right people, processes, and technology. For companies that are considering integrating RBM into their organizations, there are a variety of external resources, ranging from online training to risk/quality management consultants and RBM software vendors, that can help them navigate the decisions needed for a successful RBM technology implementation. medadnews
1 Forbes. Cleaning Big Data: Most Time-Consuming, Least Enjoyable Data Science Task, Survey Says. Available at https://www.forbes.com/sites/gilpress/2016/03/23/data-preparation-most-time-consuming-least-enjoyable-data-science-task-survey-says/#15c1f8e66f63.
2 Ray S. Clinical Teams Should Re-Think Risk-Based Monitoring Costs to Improve Their Bottom Line. Cutting Edge Information, 2013. Available at https://www.cuttingedgeinfo.com/2013/risk-based-monitoring-costs.
3 Young S. eCRF Data Correction Rates Still a Surprise to Many. Available at http://blog.mdsol.com/ecrf-data-correction-rates-still-a-surprise-to-many.