Adverse Event Reporting in Early-Phase Benign Urology Clinical Trials Using Methods Borrowed From Oncologic Clinical Trials May Inadequately Represent Tolerability

Purpose: Although most trial design features can be borrowed from oncological trials, benign urology clinical trial design has not been well described. The purpose of this study was to compare serious adverse events (SAEs) and other study characteristics of benign vs malignant lower urinary tract clinical trials to understand safety and tolerability metrics as they apply to clinical trials of benign diseases. Methods: A search was performed on ClinicalTrials.gov for phase 1 benign lower urinary tract and bladder cancer studies from 2000 to 2024. The primary end point was SAE rates. Secondary endpoints were adverse event (AE) rates, all-cause mortality, and AEs requiring therapy termination. Results: A total of 52 clinical trials were included: 18 in the benign group and 34 in the malignant group. The malignant group had significantly higher number of SAEs and AEs. At the subject-level analysis, 284/987 subjects (28.77%) in the malignant group experienced a SAE compared with 16/554 subjects (2.89%) in the benign group ( P < .001). AEs occurred in 818 subjects (82.88%) in the malignant trials and 222 subjects (40.07%) in the benign trials ( P < .001). Despite these dissimilarities, there was no significant difference in the rate of AEs requiring therapy termination. Conclusions: There are significantly higher rates of SAE, AE, and mortality in malignant bladder phase 1 trials, but no difference in therapy termination in comparison with benign trials. More specifics in AE severity, reasons for therapy discontinuation, and study dropout need to be reported to guide future benign urology clinical trials.