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

The International Council of Harmonisation (ICH) E19 guideline (Step 5), which came into effect in 2023, does not specifically mention considerations in the planning phase or analysis methods in the data analysis phase in clinical studies applying selective safety data collection (SSDC). The purpose of this article is to address the above considerations and provide points to note when implementing the four approaches presented in the guideline as examples of SSDC implementation.

We used datasets from an open-source clinical study for all analyses. Treatment-Emergent Adverse Events (TEAEs) were defined as comprehensive safety data collection (CSDC) adverse events (CSDC AEs). The SSDC AEs consisted only of CSDC AEs that met at least one of the conditions described in ICH E19 section 2.4. The SSDC was applied to the overall population (Approach 1), specific age groups (Approach 2), periods (Approach 3), and sites (Approach 4) based on four examples from ICH E19.

An Overview of TEAEs was displayed in the safety tables for each approach. For Approach 2, logistic regression analysis was performed to confirm the interactions with SSDC AEs incidence. In Approach 3, a safety table was presented by Sytem Organ Class using the person-years method. Simulations were performed to address the anticipated considerations and concerns regarding ICH E19 implementation for Approaches 3 and 4.

We provided knowledge to promote discussion, including the feasibility of planning clinical trials using SSDC, and proposed specific safety analyses and table ideas at the data analysis stage.