The Clinical Trials Transformation Initiative (CTTI) held a multi-stakeholder expert meeting on March 6 to discuss strategies for advancing the use and acceptance of disease progression modeling (DPM) in clinical trial design and decision making. Meeting attendees discussed DPM and its current applications; explored opportunities, barriers, and best practices for advancing the use of DPM in clinical trial decision making; and proposed relevant metrics for monitoring and evaluating the recognition, value, and consistent use of DPM. CTTI will be using the ideas generated during this meeting and collecting case examples of DPM application in order to identify and catalog examples of how DPM can provide value for clinical trials – with the ultimate goal of developing and disseminating recommendations that address DPM best practices. 

The maturity and potential impact of model-informed drug development (MIDD) is recognized, but knowledge sharing and clear regulatory expectations are needed to realize its widespread use. FDA’s paired meeting program and the Fit-for-Purpose initiative are examples of programs that foster engagement and transparent communication but additional communication and pre-competitive collaboration is needed between the modeling industry, regulatory agencies, and the clinical community to advance consistent application of MIDD. 

During the meeting, attributes that allow for a successful application of DPM in a given context were discussed, leveraging the results from the CTTI DPM project team scoping review and expert panel presentations.  

• Meeting attendees also discussed essential next steps for advancing the recognition,
  value, and use of DPM approaches, including the need to:
  ► Establish best practices and provide illustrative case examples.
  ► Develop a common language for disease progression modeling.
  ► Highlight the value and impact of DPM for a variety of stakeholders.
  ► Facilitate communication across stakeholders.
  ► Create metrics to monitor the changes in DPM acceptance and use within organizations and across the clinical trials enterprise (CTE). 

Overall, meeting attendees highlighted that the benefit of CTE-wide adoption of DPM would be faster, higher-quality drug development programs, and more diverse clinical trials. 

Modeling and simulations are powerful tools that can be leveraged to inform clinical trial design, support regulatory decision making, and accelerate the process of bringing treatments to patients. Despite the benefits of these methods, their use is still not widely accepted among sponsors, investigators, and regulators. Recently, there has been growing interest across the clinical trials ecosystem in advancing the use of disease progression modeling to improve clinical trial quality and efficiency and inform regulatory decision making. Disease progression modeling leverages data from a variety of sources, improving trial diversity and combining many different models to help inform decision making. 

To promote these methods, CTTI has started a new project engaging a variety of stakeholders and experts in the development of recommendations and resources for the application of disease progression modeling in clinical trials. Through this project, CTTI will generate case studies detailing successful applications of disease progression modeling, a framework for the execution of disease progression modeling in clinical trials, a set of recommendations for the implementation of disease progression modeling in clinical trials, and a review paper detailing relevant disease progression modeling applications. This project aims to improve trial and clinical development efficiency by increasing the recognition, value, and consistent use of disease progression modeling. CTTI’s work in this area will also help to advance the broader application of modeling and simulation for trial design and regulatory decision making. 

To generate recommendations and resources supporting the application of disease progression modeling in clinical trials, CTTI will utilize a variety of iterative evidence generating strategies—including a scoping review assessing the landscape of disease progression modeling applications and an expert meeting discussing the barriers to disease progression modeling application and avenues for advancement. 

Through this work, CTTI will create recommendations and resources for designing clinical trials with a quality approach that maximally leverages available data—in alignment with CTTI’s Transforming Trials 2030 vision.