Model-Based Drug Development: A FDA Critical Path Opportunity
Donald R. Stanski, MD
Stanford University
The unprecedented growth over the past decade in public and private investment in biomedical science has yielded a rich harvest of scientific discovery and technological advancement. However, there is growing concern (FDA white paper “Innovation or Stagnation: Crisis on the Critical Path to New Medical Products” http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.pdf) that there has not been a corresponding increase in the number of novel therapeutic agents produced by the pharmaceutical and biotechnology industries for diseases that do not have good therapies. The causes of this “dry pipeline” are complex and most likely arise from our still incomplete understanding of many diseases, but as well as from our inability to speed the translation of basic science information into therapeutic benefits through clinical research and drug development.
One factor that certainly plays a role in slowing the rate of appearance of novel therapeutic agents is the drug development process itself. Despite broad progress in the scientific and technical areas that underlie this important enterprise, the development of novel candidate molecular entities into safe and effective new drugs remains a laborious, inefficient, time-consuming and expensive process that has not changed appreciably in decades. To the extent that systemic inadequacies in the drug development process result in excessive risks, costs, and prolongation of safety and efficacy evaluation, society as a whole is adversely affected.
The presentation will review the role that drug regulatory science can play in the needed change in the drug development process. Specifically, the focus of the presentation will review current approaches and concepts at the Food and Drug Administration involving the concept of “Model-based Drug Development”.
Model-based drug development uses drug and disease models to aggregate and integrate knowledge, over time, for the drug effect(s), disease progression, dose response, relevant covariates and efficacy/safety/toxicity. This model-based approach becomes the basis of clinical trial simulation. The role of these concepts to improved decision-making in clinical drug development and regulatory review will be highlighted.