Pharmacovigilance: Distinguishing and Assessing Labelling, Listedness, and Expectedness
Introduction:
Pharmacovigilance, the science of monitoring drug safety, involves various critical assessments, including those related to labelling, listedness, and expectedness of adverse events (AEs). While they might seem similar, these terms hold distinct meanings and require different assessment methodologies.
Understanding the Differences:
Labelling: Refers to the information included on a drug’s packaging and prescribing
- Definition: Labelling refers to the official information accompanying a drug product, including its approved indications, dosage, warnings, precautions, and known adverse reactions.
- Significance: Assessing labelling is crucial to determine if the reported AE aligns with the known safety profile of the drug.
- Methodology: This involves comparing the reported AE with the listed side effects in the official product labelling.
- Information. This information typically includes details about known and potential AEs.
Listedness: Denotes whether a specific AE is already documented in the official product labelling.
- Definition: Listedness refers to whether the reported AE is already documented in the official product labelling or other regulatory references.
- Significance: Knowing the listedness status helps classify the AE as “*known” or “unknown” and prioritize its investigation based on its novelty.
- Methodology: This involves checking established resources like the official product labelling, drug safety summaries, or regulatory databases to see if the specific AE has been previously reported for the drug.
Expectedness: Indicates whether an AE is anticipated based on the drug’s mechanism of action, known safety profile, or pre-clinical and clinical trial data.
- Definition: Expectedness refers to the foreseeability of an AE based on the drug’s known pharmacology, mechanism of action, and pre-clinical or clinical data.
- Significance: Assessing expectedness helps differentiate between AEs directly related to the drug’s intended action (“on-target” effects) and those caused by unrelated factors (“off-target” effects).
- Methodology: This involves evaluating the reported AE in context with the drug’s known properties and mechanisms, considering available scientific knowledge and clinical experience.
Methodology Used in Assessment:
1. Labelling Assessment:
- This process involves reviewing the official product labelling and identifying described AEs.
- Discrepancies or missing information are noted, and potential updates to the labelling may be recommended if new safety information becomes available.
2. Listedness Assessment:
- This assessment involves comparing an AE reported in pharmacovigilance activities to the existing list of AEs in the product labelling.
- If the AE is not listed, it may be considered “unlisted” and requires further investigation and potential labelling updates.
3. Expectedness Assessment:
- This process involves evaluating the reported AE against the known safety profile of the drug and its mechanism of action.
- Information from pre-clinical and clinical trial data is also considered.
- Expected AEs are generally well-established and typically described in the labelling.
- Unexpected AEs, however, deviate from the expected safety profile and require heightened attention and investigation.
Importance of Distinguishing These Terms:
- Accurately distinguishing and assessing these concepts facilitates a more comprehensive understanding of the AE profile of a drug.
- Identifying unlisted or unexpected AEs can trigger further investigation, potentially leading to revisions in labelling and improving overall drug safety.
Key Differences:
The table below summarizes the key differences between these three concepts:
Conclusion:
Labelling, listedness, and expectedness are distinct yet interconnected components of pharmacovigilance. Understanding their differences and employing appropriate assessment methodologies are crucial for ensuring robust drug safety monitoring and promoting better patient care.
