ICH releases draft GCP annex, MIDD guideline
The International Council for Harmonisation (ICH) recently released new draft annex outlining principles for good clinical practices (GCPs) for sponsors and institutional review boards for collecting clinical data outside the traditional clinical trial setting, including real-world data (RWD) and data collected from decentralized trials. ICH also released a long-awaited draft guideline on model-informed drug development (MIDD).These advances were announced on 13 November following its meeting on 5-6 November in Montreal. (RELATED: ICH touts “significant milestones” reached this year in adopting and advancing guidelines, Regulatory Focus 14 November 2024).
Both guidelines were released for consultation on 6 November; the deadline for commenting is 28 February.
GCPs for decentralized trials, RWD
The ICH E6(R3) Annex 2 expands on some of the principles in the ICH E6(R3) guideline, which was released in draft form in 2023 and aims to modernize GCPs for clinical trials. (RELATED: FDA seeks feedback on ICH E6(R3)guidelines, Regulatory Focus 6 June 2023).
The new draft annex outlines a set of responsibilities and best practices for IRBs and sponsors in conducting trials and collecting data outside of the clinical trial setting.
It also covers decentralized elements in a clinical trial, which are trial-related activities conducted outside the investigator’s location, such as visits in participants’ homes, healthcare centers, or mobile medical units. It also covers data acquisition performed remotely using digital health technologies (DHTs).
Pragmatic elements reflecting trials that closely resemble routine clinical practice, and the use of RWD sources such as registries, electronic health records (EHR), hospital data, pharmacy and medical claims data or wearables are also covered.
The process of obtaining informed consent “should be tailored to reflect the design elements of the trial (e.g., decentralised or pragmatic elements).”
The guideline specifies that sponsors should engage with patients and patient advocacy groups to ensure the “successful integration” of various operational approaches and data sources used in trials. “For example, involving patients early in the design of the trial may help ensure the suitability of DHTs (e.g., mobile apps, wearables) used in trials with decentralised elements. This engagement may bring attention to areas where additional training or support may be needed (e.g., digital literacy, physical ability or lack of access to technology that may require the use of alternative approaches, specialised training or the provision of technology).”
For questions related to missing data due to participants moving to different healthcare systems or the occurrence of events between clinical visits such as discontinuing treatment when using RWD, the guidance refers sponsors to consult the ICH E9(R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials.
ICH releases long-awaited MIDD guideline
Work on ICH M15 has been progressing since May 2020 with the establishment of a discussion group on MIDD. In 2021, the discussion group announced a work plan for MIDD for integrating these approaches to drug development into existing ICH guidelines. (RELATED: ICH: MIDD concept paper coming by year’s end, Regulatory Focus 20 May 2021).
MIDD methods include population pharmacokinetics, physiologically based pharmacokinetics and biopharmaceutics (PBPK), dose-exposure-response and model-based meta-analysis.
The draft M15 guideline harmonizes expectations regarding documentation standards, model development, data used in the analysis, model assessment, and IR applications.
The guideline includes a framework for assessing MIDD evidence; a central part of this framework is developing a question that MIDD is intended to answer. It also discusses the consequences of a wrong decision based on the model.
The guideline has an Appendix I, which includes a table for assessing MIDD evidence, and an Appendix 2, which provides the content typically found in a model analysis report.
ICH E6(R3) Annex 2, ICH M15
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