Does the Epoch-Making Guideline Need Instructions for Use?: Analyzing Adverse Events Collected through Selective...

Area of Science:

• Clinical pharmacology
• Drug safety
• Regulatory science

Background:

• The International Council of Harmonisation (ICH) E19 guideline provides a framework for selective safety data collection (SSDC) in clinical studies.
• The guideline, effective 2023, lacks specific details on planning and data analysis phases for SSDC implementation.

Purpose of the Study:

• To address considerations for the planning and data analysis phases in clinical studies using SSDC.
• To provide practical guidance for implementing the four example approaches of SSDC outlined in the ICH E19 guideline.

Main Methods:

• Utilized open-source clinical study datasets for analysis.
• Defined Treatment-Emergent Adverse Events (TEAEs) as comprehensive safety data collection (CSDC) adverse events (AEs).
• Applied SSDC to overall population, age groups, periods, and sites, aligning with ICH E19 examples.

Main Results:

• Presented safety tables detailing TEAEs for each SSDC approach.
• Employed logistic regression to analyze interactions with SSDC AE incidence in age-specific groups (Approach 2).
• Utilized person-years method for safety tables by System Organ Class (Approach 3) and conducted simulations for Approaches 3 and 4.

Conclusions:

• Provided insights into the feasibility of planning clinical trials with SSDC.
• Proposed specific safety analyses and data presentation formats for the analysis stage.
• Aimed to foster discussion and practical application of SSDC in regulatory submissions.