RBM is essential in clinical trials, where sponsors monitor clinical investigations and determine any problems or risks involved with their studies that could impact participants or the general public. The FDA wants to improve this monitoring system to make it quicker and more cost effective.
On July 17th, there was a public workshop at Duke University to discuss the subjects of RBMs. Clinical investigations are conducted to make sure participants are treated ethically, and that the data is not corrupted. These investigations could include areas involving human drugs, biological products, and medical devices. Previously, to monitor these trials, a sponsor would visit every few weeks to investigate the site, but this approach cost a lot of money, resources, and was not effective in improving the quality of the investigations.
In the RBM guidance drafted in March 2019, the FDA would like sponsors to use centralized monitoring, whenever they can. The difference between centralized monitoring and on-the-site monitoring is that centralized monitoring is done in another location other than where the clinical testing is occurring. This would help sponsors gather and identify unusual data and errors, in which they can then send out sponsors on-site to the location of the clinical tests to investigate and identify any concerns. This process is called risk-based monitoring, where sponsors identify any unusual data to determine if there are any risks involved in the study that would put subjects in harm. If they do not find any errors or unusual trends, there would be no need to waste resources and time to send out on-the-site sponsors.
Risk-Based Monitoring Approach
When doing investigations, sponsors are encouraged to:
- Identify processes that are critical for participant protection, the reliability of test results, and any risks involved
- Determine the likelihood of risks, how detectible they are, and if they are acceptable or should be reduced
In the March 2019 guidance, the FDA lists some elements a monitoring plan should have such as:
- Synopsis of the study, and its objectives
- Trial-specific risks
- Any protocol deviations that would affect the integrity of the study
- Reporting of any monitoring issues
- A description of the issues found in the study
For more details, you can find the March 2019 Guidance draft here
The Public Workshop
The participants of the July 17th workshop debated if RBM even needed to be improved. Some were concerned that the change of the RBM system would delay review times, but David Burrow, the FDA OSI director, emphasized that the change in plans would not delay any reviews. Delays would cost everyone time and money. Camelia Mihaescu, the EMA Scientific Administrator, emphasized that the monitoring plan should connect with risk assessment and mitigation plans. Mihaescu also states that RBM is effective for manufacturers to understand any risks their products might have, which will make them better prepared for application submissions as well as when their products are available to consumers.