Publicly Available Clinical Trial Safety Data: Review and a Call for Standardization and Improved Reporting Practices.

BACKGROUND AND

objectivesComprehensible reporting of clinical trial safety data is essential for multiple stakeholders, including ongoing safety reporting by sponsors to the health authorities. However, the consistency and completeness of information about safety events of interest (EOIs) in public sources is not well characterized. This study examined the availability and transparency of adverse event (AE) information from public clinical trial data sources, with a focus on their utility in similar patient populations for signal detection and contextualizing rates of anticipated EOI reported as serious or severe (grade ≥ 3).

methodsA structured review of 44 EOI for ten medicinal products approved for different indications in the past 7 years in the United States (US) and European Union was conducted. The selected EOIs were events likely to be reported as serious or severe in clinical trials and additionally were either anticipated AEs or of customary high interest for the patient population. Safety data from journal publications, ClinicalTrials.gov, US Food and Drug Administration (FDA) review documents, European Public Assessment Reports (EPARs), and product labeling (US Prescribing Information, Summary of Product Characteristics) were evaluated. Parameters assessed for availability included demographic data, disease severity measures, serious AE (SAE) frequency, and exposure-adjusted rates. Clarity in approach for EOI identification also was evaluated, specifically whether based on expert adjudication or delineated pre-specified or ad hoc groupings of Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) or alternatively not specified.

resultsOverall, clinical summaries available at Drugs@FDA and EPARs provided the most information about enrolled trial participant characteristics. Greater than 95% of journal publications sampled provided information regarding enrolled participant demographics and disease severity; geography of enrolled participants was available in 43% of instances. The percentage of participants experiencing an SAE was typically available in all sources except product labeling. Information about selected serious/severe EOIs was most often found at Drugs@FDA and in the EPARs, followed by journal publications. Gaps in ClinicalTrials.gov included event adjudication details, if applicable, and lack of exposure-adjusted rates, including for medical conditions that require MedDRA PT grouping for assessment. Significant issues across all sources were frequent omission of patient years of treatment exposure and clear definitions of how EOIs were identified. Published standardized queries (e.g., Standardized MedDRA Queries) were uncommonly used across all sources.

conclusionsPublic clinical trial data sources often lack consistency and sufficient level of detail, hindering their value in contextualizing serious/severe EOI rates for novel drug development and regulatory safety reporting. Better access to treatment exposure data and more clarity in the approach to identification of EOI are essential. Enhancing the availability of key clinical trial safety information would support more robust pharmacovigilance activities and improve benefit-risk assessments in drug development.