Journal Article

Where are the harms? Underreporting of adverse events in clinical trials investigating targeted therapy for endocrine and metabolic disorders: an observational study

Marušić, Ana, Pranić, Shelly, Pavić, Maja

2025

Overview

This study aimed to assess the completeness and consistency of adverse event (AE) reporting in ClinicalTrials.gov and corresponding peer-reviewed publications for clinical trials investigating targeted therapeutics for endocrine and metabolic disorders. On September 12, 2022, a search of ClinicalTrials.gov was conducted to identify completed interventional trials investigating targeted therapeutics for the treatment of endocrine and metabolic disorders registered after September 1, 2009. The main outcome was the completeness of AE reporting in ClinicalTrials.gov and corresponding peer-reviewed journal articles. The completeness of registry reporting for serious AEs (SAEs) and other AEs (OAEs) was also assessed, as well as the all-cause mortality (ACM) data for trials with a primary completion date after January 18, 2017. In addition, the study examined the concordance in AE reporting between the two sources. Out of 7405 trials identified in the ClinicalTrials.gov registry, 92 met the inclusion criteria. All trials reported SAEs and OAEs in the registry, and all eligible trials reported ACM data. In the corresponding peer-reviewed journal publications, SAEs were reported for 86% of trials, OAEs for 91%, and ACM data for 64% of eligible trials. Among the trials with complete AE reporting in ClinicalTrials.gov and journal publications, 38% showed discrepancies in the number of participants experiencing SAEs, 86% for OAEs, and 36% for ACM data. In addition, 18% of journal articles used different terminology for reporting of AEs compared to the registry, and 60% applied different frequency thresholds. Our analysis revealed significant discrepancies between registry data and journal articles regarding AE reporting in clinical trials investigating targeted therapy for endocrine and metabolic disorders. Greater efforts are needed to enhance transparency and harmonization in AE reporting, ensuring accurate risk communication and informed clinical decision-making. Accurate reporting of adverse events (AEs) in clinical trials is essential for evaluating the safety of new therapeutics. This study assessed whether safety data reported in clinical trials investigating treatments for endocrine and metabolic disorders were consistently presented in ClinicalTrials.gov and corresponding journal publications. A total of 92 completed clinical trials registered on ClinicalTrials.gov and their published articles were analyzed. Although all trials reported serious AEs (SAEs), other AEs (OAEs), and mortality data in the registry, journal publications frequently omitted these data. Specifically, 86% of journal articles reported SAEs, 91% reported OAEs, and only 64% provided data on mortality. Even when AEs were reported in both sources, inconsistencies were common. Differences in the number of participants experiencing AEs were found in 38% of trials for SAEs, 86% for OAEs, and 36% for mortality data. In addition, 18% of journal articles used different terminology, and 60% applied different thresholds for reporting AEs compared to the registry. These findings underscore substantial inconsistencies between clinical trial registry data and peer-reviewed publications, highlighting the need for improved reporting practices. Greater transparency and standardization in AE reporting are essential to ensure the reliability of safety data for novel therapeutics. •All trials reported SAEs, OAEs, and ACM data in the registry.•SAEs were reported in 86%, OAEs in 91%, and ACM in 64% of journal publications.•Discrepancies between the sources were seen in 38% SAEs, 86% OAEs, and 36% ACM.•Different AE terminology was used in 18% of journal publications.•Different frequency thresholds were used in 60% of journal publications.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adverse Drug Reaction Reporting Systems - standards / Adverse Drug Reaction Reporting Systems - statistics & numerical data / Adverse events / Clinical trials / Clinical Trials as Topic - statistics & numerical data / ClinicalTrials.gov / Completeness / Decision making / Drug-Related Side Effects and Adverse Reactions - epidemiology / Endocrine disorders / Endocrine System Diseases - drug therapy / Humans / Internal Medicine / Intervention / Medical research / Metabolic Diseases - drug therapy / Metabolic disorders / Mortality / Observational studies / Registries - statistics & numerical data / Reporting completeness / Reporting requirements / Safety / Safety profile / Targeted therapy / Terminology / Thresholds