Module 2
Company Core Safety Information: Recommendations of the CIOMS Working
Groups & Current Regulatory Expectations –
An Overview
The CIOMS Working Groups III, V, VI, and VII published a series of suggestions and points to consider for authors of core safety labeling. Many of these suggestions are still in line with current regulatory requirements, guidelines, and expectations. One of the most important contributions of the Working Groups is having acknowledged, and drawn attention to, the principle that labeling should alert users about the existence of risks the sooner (ie, lower level of confidence that there is a causal association), the higher the relevance of the risk. The CIOMS III/V report lists several factors that are expected to lower the threshold for inclusion of safety information in core labeling. Although the CIOMS group provides detailed advice on relative threshold differences based on the relevance of risk information, its information on absolute thresholds for including safety information is less substantial than some more recent [draft] guidelines released by regulatory authorities.
While the CIOMS reports provide valuable food for thought and general advice, they cannot be used as a "cookbook" for core labeling.
The CIOMS reports provide a description of the evolution of core safety information from early clinical development (Development Core Safety Information; DCSI) to the set of Company Core Safety Information (CCSI) for a marketed product, along with suggested rules for the use of this information for determining listedness.
This module provides an overview of items in the CIOMS reports that are relevant for core labeling, as well as a first discussion of these rules vis-à-vis current labeling regulations, guidelines, expectations, and practices. Later modules contain a section-specific, in-depth discussion of the various guidelines and points to consider.
Curriculum topics of this module include:
- CIOMS' description of the "absolute" threshold for including safety information in labeling
- CIOMS' understanding of the concept "adverse reaction" for the purposes of labeling
- CIOMS' description of relevance factors that may lead to threshold modifications
- CIOMS' model of the end-user of core safety information, when implemented in local labeling
- CIOMS' suggested rules for determining expectedness – contrasted with labeling practice
- CIOMS' advice on describing the probability of adverse reactions
- The suitability of the CCDS/CCSI structure presented in the CIOMS III report