Challenges in coding adverse events in clinical trials: a systematic review

Area of Science:

• Clinical Trials
• Pharmacovigilance
• Medical Informatics

Background:

• Standardization of adverse event (AE) coding in clinical trials is crucial to minimize interpretation and ensure patient safety.
• Adverse events are categorized using predefined dictionaries like MedDRA, which are updated regularly, introducing new complexities.
• The objective of this study is to investigate interobserver variation and challenges in AE coding.

Purpose of the Study:

• To assess the reliability and reproducibility of adverse event coding in clinical trials.
• To identify challenges associated with the coding of adverse events, including interobserver variation and dictionary updates.
• To highlight the potential impact of coding inconsistencies on clinical trial outcomes and patient safety.

Main Methods:

• A systematic review of relevant literature was conducted using PRISMA guidelines.
• Searches were performed across major databases: PubMed, EMBASE, and The Cochrane Library.
• Eligibility screening of all retrieved studies was independently performed by two authors.

Main Results:

• Only 12 out of 520 unique studies met the inclusion criteria; only one examined interobserver variation, finding 12% code disagreement.
• Independent physicians noted 8% of codes deviated from original descriptions, and dictionary choice significantly impacts study summaries.
• Increased MedDRA categories complicate statistical detection of AEs; lumping techniques are underutilized, and AE censoring methods introduce potential bias.

Conclusions:

• Current evidence suggests AE coding is not consistently reliable, unbiased, or reproducible.
• The growing complexity of AE categories may hinder detection, potentially impacting patient safety.
• Awareness of these coding challenges is vital for readers of medical publications, and further interobserver studies are essential.