Empowering Clinical Development With Disease Progression Modeling: Recommendations From the Clinical Trials Transformation Initiative.

Evaluating the benefit-risk profile of a medical product requires comprehensive evidence that integrates information across development stages. Technological advances and broader use of real-world data are enabling innovative quantitative paradigms characterized by greater efficiency, patient centricity, and sustainability. Despite regulatory recognition of model-informed drug development, disease progression modeling (DPM) remains underutilized compared with more established pharmacokinetic/pharmacodynamic modeling and simulation approaches. To inform adoption decisions by clinical, regulatory, and portfolio leaders, the Clinical Trials Transformation Initiative (CTTI) developed evidence-based, cross-sector recommendations that describe when and how to use DPM in medical product development and how to effectively communicate its impactful implementation across functions. In this article, we (i) define DPM and summarize its unique value in clinical development, (ii) describe CTTI's collaborative process to generate a set of nine DPM recommendations and a practical considerations framework, and (iii) present examples of strategic development questions showing how DPM can answer high-value questions about indication, population, endpoints, and dose selection. By providing a shared vocabulary and structured questions for decision makers and modelers, these recommendations may lower barriers to DPM implementation, support fit-for-purpose use of existing and new models, and enable more efficient, patient-focused, and sustainable clinical development.