Model‐Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development

  title={Model‐Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development},
  author={P A Milligan and Marilyn J. Brown and Byron Marchant and S W Martin and Piet H. Graaf and Neil Benson and Germana de Nucci and D J Nichols and Rebecca A. Boyd and Jaap W. Mandema and Sriram Krishnaswami and S. H. Zwillich and David Gruben and Richard J. Anziano and Thomas C. Stock and Richard L. Lalonde},
  journal={Clinical Pharmacology \& Therapeutics},
The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful. In today's… 
Model-Based Drug Development: Basics and Its Application
Basic of Model-Based Drug Development is introduced from the theoretical and the practical point of view with some examples and its application for the clinical drug development of the anti-diabetes drug is shown.
Pharmacokinetic characterization of drugs and new product development
Model‐based clinical drug development in the past, present and future: a commentary
A historical account of the use of model‐based drug development in clinical drug development, the current challenges and further opportunities for its application in the pharmaceutical industry are presented.
Model‐Informed Drug Development: A Regulatory Perspective on Progress
A recent history of Modelinformed drug development at the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) is described, important developments are highlighted, and nearterm focus areas to ensure progress are described.
Acceleration of Drug Development: A Collaboration of Many Stakeholders
  • K. Reynolds
  • Medicine
    Clinical pharmacology and therapeutics
  • 2013
Collaboration of stakeholders and the use of new science and knowledge management can reduce late‐phase failure and accelerate drug development.
Why Drugs Fail in Late Stages of Development: Case Study Analyses from the Last Decade and Recommendations
This work analyzes recent late-stage failures to identify drugs where failures result from inadequate scientific advances as well as drugs where pitfalls could have been avoided.
Model‐Informed Drug Development: Current US Regulatory Practice and Future Considerations
Model‐informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision‐making process and can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy.


Model‐based Drug Development
What constitutes the key elements of MBDD and how these elements should fit together to inform drug development strategy and decision‐making are discussed.
Comparative Efficacy and Effectiveness: An Opportunity for Clinical Pharmacology
Over the past 10 or more years, the drug development paradigm has shifted radically as a consequence of the availability of generic formulations for many important drugs and the growing influence of
A Mechanistic, Model-Based Approach to Safety Assessment in Clinical Development
A generic systems pharmacology approach integrating prior physiological and pharmacological knowledge, preclinical data, and clinical trial results is presented, which allows predicting adverse event rates related to drug exposure.
Impact of Pharmacometric Analyses on New Drug Approval and Labelling Decisions
The results of a survey evaluating the impact of pharmacometric analyses on regulatory decisions for 198 submissions to the US FDA during the period from 2000 to 2008 are presented.
Has the Time Come for Predictive Computer Modeling in CNS Drug Discovery and Development?
It is suggested that an improved understanding of neuronal circuit interactions using a humanized computer‐based integration of physiology and pharmacology knowledge can substantially de‐risk new CNS projects.
A Semi‐Mechanistic Model of CP‐690,550‐Induced Reduction in Neutrophil Counts in Patients With Rheumatoid Arthritis
A semi‐mechanistic model was developed to characterize the time course of drug‐induced absolute neutrophil count (ANC) reduction in a phase 2a study and predicted the incidence of neutropenia at different doses reasonably well.
The Role of Modeling and Simulation in Development and Registration of Medicinal Products: Output From the EFPIA/EMA Modeling and Simulation Workshop
This manuscript summarizes the plenary discussion on modeling and simulation (M&S) focusing on the European perspective within plenary and breakout sessions (BOS).
Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor.
Compound 23 has exquisite selectivity for FAAH relative to other members of the serine hydrolase superfamily as demonstrated by competitive activity-based protein profiling and is being evaluated in human clinical trials.
Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects.
FAAH1 activity and fatty acid amide concentrations returned to baseline within 2 weeks following cessation of dosing at doses up to 4 mg, and there was no evidence of effects of PF-04457845 on cognitive function.