Clin Drug Investig. 2026 May 16. doi: 10.1007/s40261-026-01561-z. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: The interventional landscape for psoriasis has expanded considerably with the introduction of systemic and biologic agents, intensifying the importance of comprehensive adverse event (AE) documentation to inform safe clinical practice. While regulatory initiatives such as the Food and Drug Administration Amendments Act Final Rule (FDAAA Final Rule) were designed to enhance clinical trial transparency, disparities between AE data presented in ClinicalTrials.gov and peer-reviewed literature continue to occur, potentially complicating interpretation of publicly available harms information used in evidence synthesis and clinical decision-making. Variability in how serious adverse events (SAEs), other adverse events (OAEs), deaths, and treatment discontinuations due to AE are documented can distort safety perceptions and influence clinical practice. This study compares AE reporting between ClinicalTrials.gov and corresponding peer-reviewed publications for psoriasis clinical trials and evaluates whether completeness and concordance differ before versus after implementation of the FDAAA Final Rule.
METHODS: We performed a cross-sectional analysis using systematic retrieval of psoriasis trials from ClinicalTrials.gov with results posted between 2009 and 2024. Data on AEs-encompassing SAEs, OAEs, treatment discontinuation due to AE, and deaths-were independently abstracted by two reviewers, with disagreements resolved through adjudication. Trials were categorized according to FDA regulatory status, and variations in AE documentation were examined using descriptive statistics, chi-squared tests, Bland-Altman and funnel plots, and regression modeling.
RESULTS: The study’s primary endpoint was completeness and agreement of AE documentation between ClinicalTrials.gov and corresponding peer-reviewed publications across four predefined domains: SAEs, OAEs, discontinuation due to AE, and death. Pre-Final Rule AE reporting patterns were mixed across domains. After implementation of the FDAAA Final Rule, registry entries more consistently reported SAEs, OAEs, and mortality than corresponding publications. Although death documentation in registry entries showed improvement after the rule’s enactment, publications demonstrated persistent inconsistency. Following implementation of the FDAAA Final Rule, SAEs were present in 53% of registry records versus 40% of publications. OAEs were captured in 51% of registry entries but only 22% of publications. Disparities in SAE totals occurred in over 90% of trials, frequently with registry entries recording higher counts. Numerous discrepancies stemmed from incomplete calculations, ambiguous characterizations, or AE information confined to narrative text. Both visual and statistical assessments revealed a pattern of underreporting in publications, with minimal temporal improvement irrespective of trial scale or sponsorship type.
CONCLUSIONS: Notwithstanding current regulatory frameworks, AE documentation for psoriasis trials remains fragmented with substantial inconsistency between registry and published data. These shortcomings undermine rigorous safety assessment and evidence-based clinical recommendations. Improved patient care requires increased integration of registry data into evidence synthesis, better clarification of AE definitions, and standardized AE reporting practices.
REGISTRATION: Preregistered on The International Prospective Register of Systematic Reviews (PROSPERO; CRD420251081207) and Open Science Framework (4jaz3).
PMID:42142276 | DOI:10.1007/s40261-026-01561-z
