Landscape analysis for a neonatal disease progression model of bronchopulmonary dysplasia: Leveraging clinical trial experience and real-world data

Abstract

The 21st Century Cures Act requires FDA to expand its use of real-world evidence (RWE) to support approval of previously approved drugs for new disease indications and post-marketing study requirements. To address this need in neonates, the FDA and the Critical Path Institute (C-Path) established the International Neonatal Consortium (INC) to advance regulatory science and expedite neonatal drug development. FDA recently provided funding for INC to generate RWE to support regulatory decision making in neonatal drug development. One study is focused on developing a validated definition of bronchopulmonary dysplasia (BPD) in neonates. BPD is difficult to diagnose with diverse disease trajectories and few viable treatment options. Despite intense research efforts, limited understanding of the underlying disease pathobiology and disease projection continues in the context of a computable phenotype. It will be important to determine if: 1) a large, multisource aggregation of real-world data (RWD) will allow identification of validated risk factors and surrogate endpoints for BPD, and 2) the inclusion of these simulations will identify risk factors and surrogate endpoints for studies to prevent or treat BPD and its related long-term complications. The overall goal is to develop qualified, fit-for-purpose disease progression models which facilitate credible trial simulations while quantitatively capturing mechanistic relationships relevant for disease progression and the development of future treatments. The extent to which neonatal RWD can inform these models is unknown and its appropriateness cannot be guaranteed. A component of this approach is the critical evaluation of the various RWD sources for context-of use (COU)-driven models. The present manuscript defines a landscape of the data including targeted literature searches and solicitation of neonatal RWD sources from international stakeholders; analysis plans to develop a family of models of BPD in neonates, leveraging previous clinical trial experience and real-world patient data is also described.

Opportunities and Challenges of Disease Progression Modeling in Drug Development – An IQ Perspective

“…11 The workshop covered a range of topics of particular interest to the International Consortium for Innovation & Quality Disease Progression Modeling Working Group (IQ DPM-WG) from an initial session focusing on their public health utility with an overview of disease drug trial/disease progression modeling at the FDA with an outline and sponsor-regulator pathways that may involve utilization of disease progression modeling (DPM). 6,[12][13][14] Other session presenters overviewed quantitative models for disease progression, disease/organ on a chip microfluidic cellular tissue system, controlled human infection models and epidemiological model of disease transmission/progression, 15 and how DPMs could be leveraged as a component of a real-world data (RWD) Analytics Platform in subpopulations, focusing on data sources, predictive model landscape, and the connection of RWD to the DPM. 16 Speakers from the EMA framed the impact of DPMs on regulatory decision making, touching on models as a method to answer regulatory questions within the Credibility Framework.…”