Credits
This is a 3-credit course.
Description
Introduction to Model-Informed Drug Development (MIDD) is a 3-credit course that serves as a broad overview of applying modeling and simulation strategies to improve drug development decision-making and trial designs. Examples of applications include translational approaches from preclinical to clinical research, translation from biomarker to clinical endpoint, dose finding during Phase 1 and 2, clinical confirmation during Phase 3, avoiding the need for certain clinical trials, characterizing sources of variability in drug response, regulatory interactions and post-marketing assessment. Upon completion of the course, students will have a basic understanding of how model-based drug development can be applied to help bring new drugs to market more efficiently.
Upon completion of this course, the student will be able to:
- Discuss and appreciate the role of model-informed drug development during the following stages: discovery, preclinical, clinical, regulatory review and post-approval.
- Identify specific drug development questions or issues that can be addressed using MIDD.
- Select and apply pharmacometric method(s) used in MIDD: population PK or PK-PD, clinical trial simulation, meta-analysis, systems pharmacology, PBPK, etc.
- Contrast MIDD applications to support regulatory agency decisions versus drug development decisions within pharmaceutical industry.
- Understand the development strategies for various therapeutic areas and identify the question that needed to be answered using MIDD
- Describe MIDD approaches used to answer the above question: e.g. modeling, simulation, results, key assumptions and uncertainties.
- Explain the impact of MIDD on specific drug development examples and regulatory decisions or interactions.
- Apply MIDD concepts to all Phase(s) of drug development: preclinical, Phase 1, 2, 3, regulatory agency interactions, and post-regulatory approval.
- Explain the critical aspects of conducting clinical trials including human subject protections, Phase 1, 2, and 3 trials, regulatory requirements, and clinical data management.
- Answer specific drug development questions or issues that can be addressed by MIDD: dose selection, trial design for Phase 1, 2, or 3, go/no go, labeling, development strategy, avoiding the need to conduct a clinical trial, selecting between compounds in development, etc.
- Apply MIDD to various therapeutic areas: cardiovascular, neuroscience, metabolic diseases, oncology, rare diseases, etc.
Topics
| Week | Topic |
|---|---|
| Module 1 | |
| Week 1 | Overview of Model-Informed Drug Development; Fundamental Concepts and Basic Pharmacokinetic and Pharmacodynamic Parameters |
| Week 2 | Introduction to PK/PD; Introduction to Population PK/PD |
| Module 2 | |
| Week 3 | Introduction to PBPK; Drug Interactions |
| Week 4 | Preclinical to Clinical Scaling of PK and PD; Model-Based Meta-Analysis (MBMA) to Support Phase 3 Dose selection of Apixaban |
| Module 3 | |
| Week 5 | PBPK of Perampanel (Role in Approval); PBPK of Perampanel (Support of Monotherapy) |
| Week 6 | Model informed Drug Development to Optimize Dosing in Oncology; Model Informed Dosing Recommendation using PBPK and Translation to Prescribing Information |
| Module 4 | |
| Week 7 | MIDD in Drug Development of the anti-PD1 Mono-clonal Antibody Nivolumab; Use of Pharmacometric Approaches to Support a change in Dosing Regimen for Anti-PD-1 monoclonal Antibodies |
| Week 8 | MIDD in Oncology: Rational Dose Selection; Model-Based Meta-Analysis to Replace a Head-to-Head Clinical Trial in Type 2 Diabetes Mellitus |
| Module 5 | |
| Week 9 | MIDD in Phase 2 Development; MID3 Strategies and Antibacterial Drug Development |
| Week 10 | First Exam; Quantitative DDI Analysis for Regulatory Interactions: Case Examples |
| Module 6 | |
| Week 11 | Model-Informed Drug Development for Dose Selection and DDI; Modeling and Simulation Approaches to Support Clinical Drug Development |
| Week 12 | Introduction to IVIVC; Practical Decision Analysis Tools to Enable Key Drug Development Decisions |
| Module 7 | |
| Week 13 | Application of Model Informed Drug Development to RNAi Therapeutics; Pediatric Drug Development |
| Week 14 | Using Nonclinical Data and Physiologically-Based Pharmacokinetic Modelling to Inform on Risk of Victim Drug-Drug Interactions in Discovery’; Role of Biomarkers in Developing CNS Drugs |
| Week 15 | Final Exam |
Note: For a further breakdown of modules and course topics please see the full syllabus.
Prerequisites
There are no prerequisites for this course.
Required Materials
Recommended Textbooks:
- Title: Applied Pharmacometrics
- Authors: S. Schmidt, H. Derendorf
- AAPS Press/Springer
- 2014
- ISBN number: 978-1493913039
- Title: Rowland and Tozer’s Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Application
- Authors:. H. Derendorf, S. Schmidt
- Wolters & Kluwer
- 2019
- ISBN number: 978-1496385048
Additional reading assignments will be made available on the Canvas course site.