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Understanding Model-Informed Drug Development

Jan 10, 2025

Module 4: Foundation of Model-Informed Drug Development (MIDD)

Introduction

  • Focus on foundational knowledge of MIDD
  • Developed by experts from Satara and the Critical Path Institute
  • MIDD: A rational approach to accelerate drug development

Uncertainty in Drug Development

  • Confidence in:
    • Targets
    • Drug in question
    • Chosen endpoints
    • Regulatory decisions
  • MIDD as a method to manage uncertainty

Objectives of MIDD

  • Pathway, target, drug, risk-benefit, payer perspectives
  • Tools and techniques for decision-making:
    • Pathway pursuit
    • Correct targeting
    • Molecule development
    • Dosing
    • Patient enrollment

Drug Development Phases

  • Discovery: Target identification, metabolism, differentiation
  • Preclinical: Compound selection, first human dose, drug interactions
  • Early Clinical: Trial design, dosing, risk-benefit
  • Late Clinical: Development continuation, therapeutic window, pricing
  • Commercial: Approval, launch, lifecycle management

MIDD Strategic Plan

  • Key R&D questions to identify
  • Different levels: Disease, compound, mechanism
  • Seven themes of questions:
    • Medical need/commercial viability
    • Efficacy
    • Safety or tolerability
    • Pharmacokinetics
    • Benefit or risk
    • Clinical viability
    • Study design

Modeling Approaches

  • Types of models:
    • Empirical dose-exposure-time models
    • Semi-mechanistic PKPD models
    • Model-based meta-analysis
    • Quantitative systems pharmacology (QSP)
    • Physiologically based PK (PBPK)
    • Epidemiology models
    • Health economics and outcomes research (HEOR) models

Model Interconnectedness

  • Flow of information through modeling stages
  • Impact on decision-making during R&D
  • Iterative learning and confirming cycle

Model Selection Considerations

  • Purpose, data availability, complexity
  • Top-down vs. bottom-up approaches
  • Time and resource constraints

Types of Data

  • Individual vs aggregate data
  • Real-world data and its applications
  • System and drug property data

Extrapolation and Strategy

  • Minimize unnecessary clinical studies
  • Extrapolation strategies and validation

Conclusion

  • MIDD is integral and expected in drug development
  • Emphasizes removing uncertainty and optimizing information
  • Supported by numerous FDA guidance documents

This session highlighted the integral role of model-informed drug development in the drug discovery and development process, emphasizing its impact on decision-making and its continuous evolution in the regulatory landscape.

Full transcript