Safety reporting in head and neck squamous cell carcinoma clinical Trials: A comparative analysis of ClinicalTrials.gov data and published research

Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) is a debilitating malignancy that requires a multimodal approach in treatment, which is associated with a considerable burden of adverse events (AE). Since the 2007 FDA Amendments Act (FDAAA 801) mandates comprehensive AE reporting on ClinicalTrials.gov, the consistency of these data with corresponding peer‑reviewed publications remains unclear. This study examines the consistency of AE reporting between ClinicalTrials.gov and peer-reviewed publications for HNSCC randomized clinical trials (RCTs) conducted post-FDAAA implementation. Materials and Methods: We retrospectively analyzed AE reporting on Phase II-IV HNSCC RCTs registered on clinicaltrials.gov between September 27, 2009, and January 15, 2025. Data was extracted on participant counts and total events for serious adverse events (SAEs), other adverse events (OAEs), all-cause mortality (ACM), and treatment discontinuation. Discrepancies were defined as any mismatch in counts or reporting. Chi-square and Mann-Whitney U tests assessed differences in reporting frequencies and publication delays between trial and publication data. Results: Overall, 60 trials met inclusion criteria. All 60/60 (100 %) trials reported participants affected by SAEs versus 43/60 (71.7 %) publications (p < 0.05), of which 33/43 (76.7 %) showed discrepant counts. Likewise, 60/60 (100 %) trials versus 22/60 (36.7 %) publications reported participants affected by OAEs (p < 0.05), with 18/22 (81.8 %) mismatches. Among 24/24 (100 %) trials completed post‑2017, ACM was reported on ClinicalTrials.gov versus 15/24 (62.5 %) publications, and 22/24 (91.7 %) of those pairs differed. Participant discontinuations due to AEs appeared in 17/60 (28.3 %) registries versus 39/60 (65.0 %) publications (p < 0.05); of the 15/17 (88.2 %) with both sources reporting, 9/15 (60.0 %) had discordant counts. Conclusion: Substantial inconsistencies in AE, mortality, and discontinuation reporting persist between ClinicalTrials.gov and peer‑reviewed publications of HNSCC RCTs. To uphold transparency and patient safety, enhanced technical safeguards on registry platforms and stricter journal policies, such as mandatory discrepancy checklists, are urgently needed.