Tracking outcome changes in benign prostatic hyperplasia trials: a version history review of ClinicalTrials.gov...

Benign prostatic hyperplasia (BPH) is a common condition with trials that frequently rely on subjective outcomes. While federal regulations require prospective outcome registration in ClinicalTrials.gov, modifications to these outcomes are permitted and often unjustified, potentially compromising transparency and interpretability. This study examined the frequency, timing, type, and transparency of prespecified outcome modifications in BPH trials.

We conducted a registry-based cross-sectional analysis of interventional BPH trials registered on ClinicalTrials.gov between January 18, 2017, and December 31, 2024. Eligible trials enrolled adult males, reported posted results, contained prespecified outcomes in both original and most recent registry versions, and were linked to peer-reviewed publications. Modifications were categorized by type (e.g., additions, removals, rewordings), timing, and severity. Key variables included the Outcome Load Index (OLI) and a Severity-Weighted Change Score. Statistical analyses included Cochran's Q tests, Kaplan-Meier time-to-event analysis, and correlation tests.

Of 1383 records screened, 36 trials met inclusion criteria. All trials (100%) exhibited at least one outcome modification, none of which were justified. Modifications occurred exclusively after primary completion; half occurred before publication and half after. Minor rewording and broad-to-specific definitional shifts were most common. Changes were significantly more frequent in secondary outcomes (p < 0.01). Severity scores varied widely but were not consistently associated with funder or intervention type. OLI showed weak correlation with modification frequency (r = 0.17).

In this registry-based analysis of BPH clinical trials, outcome modifications were universal, occurred exclusively after primary completion, and were never justified in either the registry or corresponding publications. These findings highlight a persistent gap in transparency that could affect the interpretability of trial results. Greater oversight of registry version histories and stronger disclosure standards are needed to ensure the credibility of outcome reporting in BPH research and beyond.

Registered on the Open Science Framework. The study was additionally submitted to PROSPERO; the OSF registration is the protocol of record. Registered on July 17, 2025.