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 pharmacometrics 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 the 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 MIDD can address: 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 |
|---|---|
| Week 1 | Course Overview and Overview of Model-Informed Drug Development |
| Week 2 | Introduction to Population PK-PD; The usage of monoclonal antibody models for the expansion of the Xolair (omalizumab) dosing table to support an unmet medical lead |
| Week 3 | How technical pieces of MIDD are included in submissions for an IND/CTA/NDA/MAA, and best practices for including this information |
| Week 4 | MIDD for New Drug Development |
| Week 5 | TBD; MIDD to support regulatory concerns in pediatrics |
| Week 6 | Streaming approval for generic drug inhalation |
| Week 7 | MIDD Dose Optimization Oncology; MI Dosing Recommendation using PBPK and Translation to Prescribing Information |
| Midterm Exam | |
| Week 8 | Translational drug development using MIDD |
| Week 9 | MIDD Approaches for Vaccine Development; Model-Based Approach to Select the Dose Regimen of GBT021601, a Next-Generation Sickle Hemoglobin Polymerization Inhibitor in Healthy Volunteers and Patients With Sickle Cell Disease |
| Week 10 | Translation Modeling: How to predict FIH dose for clinical trials?; Using Clin. Pharm. and PMX to accelerate cell therapeutics development: A Patient’s CAR-T journey |
| Week 11 | MIDD applications when organ impairment is a determinant of dose; Pharmacometric Approaches for change in Dosing Regimen for Anti-PD-1 monoclonal Antibodies |
| Week 12 | TBD |
| Week 13 | No classes – Thanksgiving Break |
| Week 14 | Model-Based Meta-Analysis (MBMA) to Support Phase 3 Dose Selection of Apixaban; Decision-making in Pharma R&D with a focus on MIDD |
| Week 15 | Optimizing efficacy and minimizing toxicity through data-driven drug dose and schedule selection; Course closure and overall discussion |
| Final Exam |
Note: For a further breakdown of modules and course topics please see the full syllabus.
Prerequisites
Introductory knowledge of PK modeling and simulation.
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 Applications
- Authors:. H. Derendorf, S. Schmidt
- Wolters & Kluwer
- 2020
- ISBN number: 978-1496385048
Additional reading assignments will be made available on the Canvas course site.