Understanding Labelling, Listedness, and Expectedness of Adverse Drug Reactions (ADRs)
Adverse Drug Reactions (ADRs) are a significant aspect of pharmacovigilance and patient safety. Proper categorization and understanding of ADRs are critical for healthcare professionals and regulatory authorities to mitigate risks and improve therapeutic outcomes. Among the key concepts in ADR evaluation are labelling, listedness, and expectedness. This blog aims to clarify these terms and their importance in pharmacovigilance.
What is Labelling in ADRs?
Labelling refers to the official documentation of a drug’s properties, usage, and safety information the manufacturer provides. It includes:
- Package Inserts: Instructions for healthcare providers and patients.
- Summary of Product Characteristics (SmPCs): Comprehensive details about the drug, including pharmacodynamics, pharmacokinetics, indications, contraindications, and potential adverse effects.
Labelling acts as a reference to determine whether an observed ADR is documented and known.
What is Listedness?
Listedness refers to whether a specific adverse reaction is included in the product’s labelling (e.g., package insert or SmPC). Listedness is categorized as:
- Listed ADRs: Reactions already documented in the labelling based on clinical trial data or post-marketing experience.
- Unlisted ADRs: Reactions not mentioned in the product labelling, requiring further evaluation and potential updates to the drug’s safety profile.
What is Expectedness?
Expectedness is closely related to listedness but emphasizes the predictability of an ADR. Regulatory agencies, such as the FDA and EMA, use this concept to classify ADRs as:
- Expected ADRs: Reactions consistent with the drug’s known safety profile and documented in the labelling.
- Unexpected ADRs: Reactions that are not anticipated based on existing safety information, even if pharmacologically plausible.
Key Differences Between Listedness and Expectedness
- Context of Use:
- Listedness applies to the specific drug’s labelling.
- Expectedness considers broader scientific understanding and regulatory definitions.
- Scope:
- Listedness is confined to the product’s labelling.
- Expectedness can extend beyond labelling to include mechanistic plausibility.
Importance in Pharmacovigilance
- Risk Management: Identifying unlisted and unexpected ADRs helps in assessing and mitigating drug-related risks.
- Regulatory Reporting: Regulatory authorities require mandatory reporting of serious and unexpected ADRs for timely safety updates.
- Patient Safety: Clear differentiation between listed, unlisted, expected, and unexpected ADRs enhances clinical decision-making and minimizes risks.
Examples
Listed and Expected ADR:
- Nausea with metformin is a well-documented and anticipated side effect.
Unlisted and Unexpected ADR:
- Severe anaphylaxis with a commonly used vaccine not previously reported in the labelling or literature.
Conclusion
Understanding the labelling, listedness, and expectedness of ADRs is fundamental for healthcare professionals involved in drug safety monitoring. Proper categorization aids in regulatory compliance, enhances patient care, and ensures that drugs are used safely and effectively. Collaboration between manufacturers, regulators, and healthcare providers is essential for maintaining up-to-date and accurate drug safety information.
