In March 2019 I had the opportunity to interview Jennifer Newman, Global Project Leader, Regulatory Affairs/Clinical Operations for Celldex Therapeutics. Newman was once part of the largest implementation of RBM and was able to share insights from her experience. Specifically, she was able to discuss the benefits and challenges of RBM and what companies should be prepared for when adopting the technology. In this video, Newman discusses how companies might want to implement an RBM solution.
Ed Miseta: For a company that wants to get into risk-based monitoring, there are many ways to do it and different solutions they can incorporate. Are you able to give an overview of what those different solutions are and how they would work?
Jennifer Newman: There is no prospective way of doing this. There are tools out there from industry, particularly TransCelerate. There are very large spreadsheets available to anybody, not just TransCelerate company members, that are basically laundry lists for companies to use.
They basically pulled all their ideas and what could possibly go wrong in a clinical trial and tried to capture it. For most people, I think this approach would be a little daunting. If your goal is to implement a quality management system, you first need to convince management that it is important. Then you have to show them how you’re going to do it. Then you need to open that spreadsheet, have a meeting, and bring everyone in go through the items and rank every single piece of data according to their importance for that particular study. Then, for every future study, you’re going to have to do that all over again. It’s not easy.
I think the size of those documents, the sheer volume of information, and confusion over where to even begin is giving people pause. That’s not necessarily a bad thing, because I’m not a firm believer in throwing everything into a spreadsheet and managing it that way.
I was involved in one of the very first studies that was part of TransCelerate’s effort to implement risk-based monitoring. It was a very large study in diabetes. The study was ongoing when it was implemented, and the decision came from the top-down. The implementation decision was made because it was expected to cut 50 percent of the monitoring costs from this huge clinical study.
The budget for the study was in the hundreds of millions, so you can imagine how that got everyone’s attention. The system was very rudimentary, especially compared to the more sophisticated systems we have today. It was a system where things were flagged, and there were algorithms and you hit certain percentages within your metrics. It’s all very calculated. Your spreadsheet would turn red in certain fields, and the team would focus on those red flags. In retrospect, I don’t know if it was a very interesting experience, because people will march in whatever direction you tell them.
For example, if you say, “Here’s a spreadsheet that shows you the issues in your study – take care of them,” they are going to start to focus on getting those red cells out of that spreadsheet. Unfortunately, I don’t think it’s that simple and I don’t think that you really want to rely on something like that.
Today, solutions are a bit more sophisticated, and we now have dashboards, for example. I think the takeaway for me is that you still have to be looking at things, holistically and qualitatively in addition to quantitatively, and really understand the drivers of your particular study. That is how you will get the most cost benefit from your time and effort.
I think, for implementing these kinds of systems, it really starts with the beginning of the study and doing a very, very thorough risk evaluation. You need to take what you learned from past studies and past experiences and use that knowledge to build what we’re going to look at and what we’re going to act on, especially if things start to go south.
To me, that is good, effective risk-based monitoring, and it’s not just about necessarily reducing source data verification. It’s about bringing the intelligence of quality management into a centralized point and making sure that the study team leadership is having those important discussions.
Miseta: I think one of the concerns a lot of people have is quality, and it seems like if you do this the right way, if you plan it correctly and implement it correctly, that you could actually have more quality built into the system than you did in the past, even with less monitoring.
Newman: Yes, and I think that’s what ICH is trying to get at. I think the translation of it is people are struggling, and I understand that. But really, it’s all about the quality.