The International Council for Harmonisation (ICH) continues to advance global standards in drug development and clinical practices with its recent guidance documents. This blog explores three newly released or updated guidances—M15: General Principles for Model-Informed Drug Development, E6(R3): Good Clinical Practice (Annex 2), and E11A: Pediatric Extrapolation—detailing their objectives, key principles, and implications for pharmaceutical and clinical research.
What is MIDD?
Model-Informed Drug Development (MIDD) involves the use of mathematical, statistical, or simulation models to inform and enhance drug development decisions. The M15 guidance provides general principles to harmonize the application of MIDD globally, ensuring its effective integration into regulatory submissions.
Objective: Promote the use of MIDD to improve decision-making, reduce development costs, and accelerate timelines.
Scope: Covers pharmacokinetic (PK), pharmacodynamic (PD), disease progression, and exposure-response models.
Best Practices: Encourages transparent documentation, appropriate validation, and context-specific model applications.
MIDD facilitates precision in dose selection, trial design, and benefit-risk assessments, aligning with the industry's push toward data-driven drug development.
For detailed guidance, refer to the M15 Guidance here.
What is GCP Annex 2?
The E6(R3) guideline builds upon the foundational principles of Good Clinical Practice (GCP), introducing Annex 2 to address situations where novel trial designs and digital tools are employed. This annex supports the integration of decentralized trials, adaptive designs, and patient-centric approaches.
Flexibility in Trial Conduct: Provides guidance on accommodating innovative designs like hybrid trials and the use of digital health technologies.
Risk-Based Quality Management: Emphasizes identifying and mitigating risks through early planning.
Investigator and Sponsor Responsibilities: Clarifies roles in novel trial settings, including remote monitoring and e-consent.
Annex 2 ensures the ethical and scientific integrity of trials amidst evolving methodologies, paving the way for more inclusive and efficient clinical research.
For detailed guidance, refer to the E6(R3) Annex 2 Guidance here.
Guidance: E11A: Pediatric Extrapolation
What is Pediatric Extrapolation?
The E11A guidance outlines a structured approach to applying data from adult populations—or other pediatric subgroups—to infer outcomes for pediatric patients. This strategy minimizes unnecessary trials in children while ensuring effective and safe therapies.
Framework for Extrapolation:
Use of existing data to predict safety, efficacy, and dosing in pediatric populations.
Assessment of disease similarity across age groups.
Modeling and Simulation: Encourages leveraging MIDD approaches to strengthen extrapolation efforts.
Data Gaps: Identifies where additional pediatric-specific data are needed.