Bremelanotide for Low Sexual Desire in Women: Small Effects and Questionable Outcome Measures

8 of 11 clinicaltrials.gov-specified efficacy outcomes were unpublished, including FSDS-DAO total score, FSFI total score, FSFI arousal domain, and FSEP-R items. Analyzed unpublished outcomes showed effect sizes from nil to small. Published categorical response outcomes lacked validity evidence. Nearly all outcomes suggesting modest benefits were likely post-hoc.

Critical review and reanalysis of the Phase III RECONNECT bremelanotide trials. Examined measurement properties and validity evidence for all efficacy outcomes. Obtained and analyzed previously unpublished data from 8 of 11 pre-specified ClinicalTrials.gov outcomes. Evaluated whether published categorical response definitions had supporting validity evidence.

Drug approval should be based on meaningful clinical outcomes measured by validated tools. This analysis raises concerns that bremelanotide was approved based on modest improvements in outcomes that may not actually measure what they claim to measure in the target population. This has broader implications for how drugs for sexual health conditions are evaluated.

The approval of drugs for subjective conditions like sexual desire disorders is particularly challenging because outcomes rely on self-reported questionnaires. This critique highlights a broader issue in pharmaceutical research — selective outcome reporting and the use of unvalidated measures can make modest drug effects appear more clinically meaningful than they are.

This is a secondary analysis that cannot definitively prove the outcome measures are invalid — it can only demonstrate the absence of supporting validity evidence. The authors did not have access to individual patient data, limiting the depth of their reanalysis. Their critical perspective may underestimate clinically meaningful subjective improvements that are difficult to capture with standardized scales.