Integrating Risk-Based Monitoring Into Your Clinical Organization
Site monitoring is compulsory in the life sciences industry. For every single clinical trial conducted, sponsors are required to monitor investigative sites for adherence to protocol and protection of trial subject safety according to the applicable regulations, such as those from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Until recently, the industry standard practice has been to provide generalized quality control based on a prescribed monitoring visit schedule with the same frequency for all clinical trials and investigative sites, regardless of the risk associated with each site.
The old standard is changing. The life sciences industry is moving toward a risk-based monitoring (RBM) approach to achieve regulatory compliance of clinical trial sites. The reality is that some sites and clinical trials require much more oversight than others. Current assessment models give equal attention to all investigative sites and clinical trials. This current method wastes a great deal of time and resources without even effectively assessing risk. RBM is designed to focus on the investigative sites that present the greatest potential risks to human subjects and data quality rather than wasting undue efforts on sites that require minimal monitoring.
A Move Toward RBM
Earlier this year, the FDA published industry guidance on RBM in clinical trials, titled Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring. EMA published a reflection paper titled Reflection paper on risk-based quality management in clinical trials, which includes details on RBM. These papers detail what these agencies believe are the best approaches to RBM, and carry considerable weight with life science companies. The FDA and EMA have made some game-changing recommendations. Rather than rout review of every last piece of data from clinical investigator sites, they recommend that clinical trial teams take an approach that focuses attention on the investigative sites with the highest risk.
This risk-based approach starts with a thorough assessment and documentation of the risk profile for each individual study. From this risk assessment, a plan can be derived to assess quality indicator signals from the conduct of the trial. Including RBM shifts the monitoring emphasis from on-site monitoring to centralized monitoring. This does not necessarily reduce the amount of monitoring for a clinical trial, but it changes the emphasis of how monitoring is conducted. Instead of countless hours spent by a clinical trial monitor poring over clinical trial and source documents, technology will be used in new ways by the clinical trial monitor and study team to conduct clinical trial monitoring.
National Institutes of Health (NIH), oncology cooperative groups and ISIS (International Study of Infarct Survival) clinical trials have successfully conducted RBM according to the FDA. The initial site visit continues to be conducted, but subsequent site monitoring visits are based on the objective, design, complexity, size and endpoints of a clinical trial.
What This Means for Your Organization and the Investigative Sites
Developing efficient, effective, risk-based approaches to site monitoring is in everyone’s best interests. There are many factors to consider when it comes to monitoring investigative sites for clinical trials, though. The outcome affects more than just the site monitors. It affects a team of internal experts at the clinical trial sponsor and the investigative sites. To ensure the quality and compliance of investigative sites, clinical trial sponsors can rely on field-based monitoring, or look to more centralized (remote) monitoring. This centralized option may enable the clinical trial sponsor to streamline monitoring, shift more resources inside and take more control over the process.
For centralized monitoring to realize the full potential of its efficiencies, the clinical data must be entered in an Electronic Data Capture system (EDC) by the investigative sites in a timely manner. The longer a site delays data entry into the EDC, the greater the potential risk to the human subjects and data quality. Additionally, the quality of the data entry into EDC is also important. The fewer data entry errors in EDC, the fewer data corrections will be required during the data clean-up process. The timely, quality data entry to the EDC can be a contracted incentive for both an investigative site and a Contract Research Organization (CRO) if the trial monitoring is outsourced.
Likewise, the timely quality data clean-up process can be an incentive for the data management group. The data management group will need to process the data from the EDC to the clean clinical database management system (CDMS) in less time – 100 days to clean clinical data will no longer be acceptable.
There are many different operating models to choose from when taking this RBM approach. A team of experts working together to collect regional data into a central repository can often make more diverse kinds of assessments by looking at statistics as well as qualitative data. It is important to consider the unique structure, history and goals of the organization and the clinical trials in question before deciding whether to utilize distributed assessments, restructure the roles and organization of the trial team or make any other major changes to the monitoring approach.
The stakes are high for implementing more efficient and effective approaches to the monitoring of investigative sites. The average clinical trial costs approximately $100 million to manage and implement, and as much as $30 million of that is typically spent on oversight and monitoring. Cutting the costs of site monitoring can make a big impact, leaving more money to invest in developing and releasing better products to the public. The challenge is doing so while protecting the human subjects and preserving the integrity of the clinical trials without unnecessarily impeding the trial team in any way.