Outcome Modification and Disclosure Practices in Sinonasal Clinical Trials: A Registry-Based Cross-Sectional Analysis

To characterize the frequency, nature, timing, and transparency of prespecified outcome modifications in interventional trials for inflammatory sinonasal disease registered on ClinicalTrials.gov.

We identified interventional trials for inflammatory sinonasal disease registered on ClinicalTrials.gov with published primary results. Earliest and most recent registry versions were compared to identify substantive modifications to primary, secondary, and other prespecified outcomes. Modifications were categorized by anticipated interpretive impact (high or moderate), and timing relative to trial completion and publication was recorded. Disclosure of outcome modifications was assessed in registry records, including posted protocol documents when available, and in associated peer-reviewed publications. Descriptive analyses summarized modification patterns, and unadjusted regression analyses explored factors associated with high-impact modifications.

Seventy-two trials met inclusion criteria. Substantive outcome modifications occurred in 68 trials (94.4%), with primary outcomes affected in 59 trials (81.9%). The median number of substantive modifications per trial was seven (interquartile range, 3-10). Common modification types included clarification or increased specification, changes in assessment timing, outcome additions, and complete redefinitions involving changes in measurement instruments or methodologies. All recorded modifications were entered after primary completion or publication. Disclosure was uncommon: 3 of 68 modified trials (4.4%) acknowledged changes in the registry, 1 (1.5%) in the publication, and 4 (5.9%) in either source. Trials prespecifying more than three outcomes and trials completed after implementation of the FDAAA Final Rule had lower odds of high-impact modification.

Outcome modifications are frequent in sinonasal trials but are rarely transparently documented. Given the central role of symptom-based, quality-of-life, and endoscopic outcomes in rhinology, clearer documentation of outcome changes is essential to support interpretability and evidence synthesis.

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