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I was lucky to be privy to early results from research being conducted on Risk-Based Monitoring. Without giving away all the secrets, we have to wait for the white paper report, I can confidently say that it’s going to take awhile to achieve true risk-based monitoring because most large sponsors are looking for actual implementation successes with an approved drug as their model.
Price Waterhouse Coopers, in this article, outlines the following four types of risk-based monitoring: Reduced Monitoring, Targeted Monitoring, Centralized Monitoring and Remote Monitoring. In this scenario, many respondents in the aforementioned research, are doing some sort of RBM. For example, on-site monitoring based on triggers or risks is Targeted or “Triggered” monitoring.
Others report remote monitoring via EDC, however, most are not reducing the monitoring less than 100% SDV. Most large pharma apparently is comfortable with its 100% SDV although studies and research, some cited in the final FDA guidance on this topic, finds 100% SDV not cost effective, or data effective for that matter.
And Centralized Monitoring, the one strategy that is left, the one that the FDA Guidance says “FDA encourages greater use of centralized monitoring practices, where appropriate, than has been the case historically, with correspondingly less emphasis on on-site monitoring”—is on the radar for the respondents, but facing obstacles for implementation.
The FDA Guidance further is listed as the top resource for these industry executives, but many say it’s light on specifics, as well as insight into cutting edge technologies. I find that would be true of most regulatory guidances. The FDA doesn’t really tell you what to do or specifically how to do it, and on the top of each page of the document it says “Contains Nonbinding Recommendations.”
Now for a little more insight into technology, sponsors and CROs could look at the TransCelerate BioPharma Methodology paper also found with the FDA and EMA papers at www.appliedclinicaltrialsonline.com/rbm under Resources. Here they table what the Risk-Based Monitoring Committee found as System Requirements and Preferred System Attributes, but not specific vendors or products.
But if you are looking for hard examples and case studies for RBM, certain companies have them. GSK Vaccines, which was involved in the pilot testing of the algorithms developed into a recently launched intelligent statistical modeling program. Bayer, which I have heard Johann Proeve present at a CBI conference on its centralized data management using signals from EDC to inform monitoring and/or site issues. Mike Luker, on the RBM committee for TransCelerate, is currently piloting its methodology at Lilly. So they will have true-to-life examples coming soon.
But the golden chalice, the assurance that RBM has been used in trial for a drug that has been approved? Not so much. In medical devices, yes. Drugs, no takers.
So the conundrum exists. If you don’t try RBM, you won’t have a case study. If you don’t have a case study, others won’t follow your example. Because even though the FDA says it’s OK to use Centralized Monitoring, it is proving to take some convincing.