TransCelerate Launches Quantitative Metrics Toolkit and Discusses RBM Advancement

TransCelerate recently released an interactive guide on Risk Based Monitoring (RBM), and has also announced the launch of a Quantitative Metrics Toolkit that suggests metrics for use in clinical trials. Moreover, the RBM paradigm continues to transform clinical operations and risk management, and there are synergies between the evolving areas of quality management and mHealth and the RBM methodology. In this interview, Justin Stark, Head and Director of Risk-Based Monitoring and Standards at UCB will discuss the RBM toolkit, and advancements in RBM.

Moe Alsumidaie: How is the RACT being utilized in practice to enable risk-based approaches, and what feedback is coming out of TransCelerate member companies, now that the biopharmaceutical industry has had several years to utilize RACT?

Justin Stark

Justin Stark: The general consensus and feedback that we hear amongst our Member Companies is that the adoption and use of RACT helps facilitate risk assessment, planning and evaluating opportunities for quality by design to avoid risks in clinical trial planning and set up. There seems to be consensus that either early on, or as companies get more experienced, the RACT evolves to become better contextualized to a company’s own particular clinical development operational model. The RACT becomes supplemented with additional questions as companies discover more about how to use the tool, which makes the tool more robust over time. It also helps study teams think about relevant risks that are important to the study and to patients as they begin to plan for their clinical trials.

MA: Can you elaborate on feedback you’ve received regarding change management associated with RBM implementation?

JS: The change management across a variety of stakeholders cannot be understated, particularly with clinical monitoring personnel. One of the areas where companies are trying to change the paradigm and help these stakeholders navagate these changes by ensuring cross-functional awareness that provides the bigger picture of how risk is effectively being managed across the study. Companies are trying to avoid risk through quality by design or ensure robust plans are in place to enable effective, proactive and ongoing data surveillance that can detect these risks. This enables timely proactive intervention to prevent risks from turning into an issue that compromises patient safety, or the objectives of a trial. Similarly, another area where change management is important is consideration of study sites and helping investigators and site staff to better understand what RBM is as well as what it is not.

MA: How is RBM impacting study operational outcomes?JS: TransCelerate member companies that are implementing RBM are voluntarily sharing what they observe across their trials on a regular basis. Several metrics have been defined: metrics that tie to patient safety, overall quality of the study, data flow and ensuring timeliness of data. Those metrics are key performance indicators for RBM’s impact thus far. Generally, in the majority of cases, you see pretty favorable results across all of those metrics from the Transcelerate member companies that are implementing RBM. There are some studies for each of these metrics where member companies report worse performance compared to their relevant benchmarks but these cases are in the minority and unfortunately we don’t have the context to evaluate what might be driving those particular trends. However, RBM is still evolving, becoming better understood, and we definitely are seeing improvements in our metrics and increasing adoption of the RBM methodology.

MA: Why has TransCelerate developed the interactive RBM guide? How is it expected to help biopharmaceutical organizations better implement RBM?JS: It is to everybody's benefit to have some level of common understanding and a framework as to what RBM is and what it isn’t. The intention behind the RBM interactive guide is to provide the broader community of stakeholders (including other sponsors that are not members of TransCelerate) additional context for what has been learned and developed by TransCelerate over the last few years. It is also there to help facilitate the adoption and implementation of RBM, and it’s easy to reference. With some of what's happening in the regulatory landscape, regulators are indicating these risk-based types of approaches are what they expect. Putting the RACT, RBM interactive guide and other RBM assets into the public domain and making it easily accessible enables stakeholders to access a lot of information. Also, there is a level of credibility because the information has been vetted and informed by the experiences of TransCelerate member companies who have been working in this space, and piloting and implementing RBM over the last several years.

MA: There are several RBM technologies that are offering free RACT workflows in their systems. Is this the type of progress that TransCelerate has been expecting from its initiatives?JS: Part of the intention behind this initiative was to build and scale a risk-based methodology with the foundation of consistency, and that allows us to partner well with other enterprises in the industry, whether they are a CRO, other service provider, or technology platform. There is still continued evolution that needs to occur, and we are also going to begin to see convergence with a lot of the other key enablers, like the work coming out of the TransCelerate QMS workstream, CTTI and other initiatives across the industry. This will continue to transform the clinical development paradigm to the extent that we can build off some common frameworks to benefit all of us, because it gives consistency that allows there to be scalable enablers, which can then help us transform the way we run clinical trials.

MA: What is going to happen in the future with RBM?JS: I believe that RBM is going to be the de facto way that we run our clinical trials and plan for them in the future. As RBM gains maturity, we need to heed the convergence between quality by design and quality management systems supported by robust knowledge management, to enable us to effectively identify risks and proactively plan for them. Not just based on the experience of individual stakeholders that might be within a study team or working on clinical development program, we need to also more effectively harness the experience of the institution and broader industry. We need to draw from our lessons learned in addressing similar issues many times over. Technology and the capability to effectively harness data and metadata and using it as an asset will also enable us to transform that paradigm. It makes me quite optimistic for where we will go as an industry from here.

MA: Do you think mHealth will contribute towards risk reduction strategies in clinical trials?JS: mHealth's emergence will be very complementary to the RBM methodology. The more we can collect data directly at the source, pick up signals, and have that data available in near real-time, the better positioned we will be to identify and manage risk with proactive interventions. When that capability is enabled and supported by a robust framework, leveraging quality by design, effective risk assessments and planning upfront, we ensure that we are vigorously leveraging technology and our capability to acquire and analyze the data effectively. By doing so we can use this data to more optimally manage and respond to what is important to our trials; ensuring patient safety and rights along with the validity of the data important to evaluating the primary and secondary objectives of our trials.

Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.