Module 4
Alerting Users About Risks -
General Considerations
The Adverse Reaction section is commonly considered the CCDS section that is most challenging to design and populate – even if the authors are familiar with the general criteria for identifying an appropriate set of "adverse reactions for the purposes of labeling." Medicine users (patients/consumers, healthcare professionals) expect this section of local labeling to contain useful information. Regulations and regulatory guidelines reflect these expectations. They require meaningful tables and listings, the inclusion of additional information where relevant, and an informative discussion and presentation of important topics (if not provided in other sections of the label).
A CCDS' Adverse Reactions section that has been populated only with "bare bones data" such as tables and lists of terms, sorted by primary MedDRA SOC and enriched by incidence rates and frequency terms, is usually not a sufficient basis for drafting local labeling and achieving "harmonized" section content across markets. Safety labeling harmonization means more than ensuring that the same set of terms/concepts can be considered expected for safety reporting purposes.
A good understanding of the various formats, of content requirements, and of the underlying logic of Adverse Reactions sections in local labeling makes it possible to see commonalities and differences. It therefore can guide the generation of useful CCDS content and optimal presentation of this content. However, CCDS Adverse Reaction section content and layout is also shaped by the role the CCDS plays in driving local labeling content at a specific point of a product’s life cycle and by the degree the company releases additional, other reference documents to address the specific needs of some markets.
Many perceive the provision of information about the probability of adverse reactions ("frequency information") to be a task of particular complexity. There are very different approaches to informing about adverse reaction probability, across markets and even within a market. Understanding the logic, the informational value, and the shortcomings of these approaches is important for deciding which information to include in a CCDS, as is – again – knowledge about alternative ways of meeting the needs of certain affiliates and some company-internal stakeholders.
Topics of this module include:
- Review of current local requirements and guidelines on the content and format of the Adverse Reactions section
- Overview of typical complexities and challenges
- Creating a truly global Adverse Reactions section - Is it possible?
- What exactly should we provide proactively to meet affiliate needs around the globe, and how can we capture this information?
- Should the Adverse Reactions section be limited to risks that are known from use in humans?
- Are there exceptions to the rule that only "adverse reactions for the purposes of labeling" are provided? Is there a place/use for mixed ADR/AE tables in core labeling?
- A simple algorithm for deciding how to "slice and group" information for inclusion in adverse reaction tables
- For CCDS/CCSI: Splitting or not splitting the section in Clinical Studies and Postmarketing subsections/tables
- Appropriate use of SOCs and allocation of adverse reactions - How to make up for the separation of information caused by SOCs?
- Criteria for sorting adverse reaction within a SOC
- Where to put and how to present class reactions
- Which frequency information to provide, and how
- When and how to provide information about the potential severity of adverse reactions
- Use of local standard statements in core labeling
- Can everything in the Adverse Reactions section be mandatory for local submission?