ABSTRACT

Efficacy outcomes are only informative to the extent that they are validated. We examined the measurement properties of efficacy measures from the phase III (“RECONNECT”) bremelanotide trials for hypoactive sexual desire disorder (HSDD) in women. Continuous efficacy outcomes, including a) the Female Sexual Function Index (FSFI) and its Desire domain (FSFI-D) and b) the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) and its item assessing distress due to low desire (FSDS-DAO #13) have questionable, at best, validity evidence for women with HSDD. We found no validity evidence for previously published categorical treatment response outcomes from the RECONNECT trials. All efficacy results should be reported, but results on 8 of the 11 clinicaltrials.gov-specified efficacy outcomes were heretofore unpublished (including FSDS-DAO total score, FSFI total score, FSFI arousal domain, and items from the Female Sexual Encounter Profile-Revised). We analyzed these outcomes, upon which effect sizes ranged from nil to small. Several other continuous and categorical outcomes generated modest apparent benefits, though nearly all of these outcomes were likely derived post-hoc. Across RECONNECT trial data from two prior publications and the current study, bremelanotide's benefits are statistically modest and limited to outcomes for which scant evidence of validity among women with HSDD exists.

摘要

疗效结果仅在经过验证的范围内提供信息。我们检查了 III 期（“RECONNECT”）布雷默浪肽试验中针对女性性欲减退症 (HSDD) 的疗效测量的测量特性。连续疗效结果，包括 a) 女性性功能指数 (FSFI) 及其欲望域 (FSFI-D) 和 b) 女性性困扰量表-欲望/唤醒/性高潮 (FSDS-DAO) 及其评估因以下原因引起的困扰的项目低欲望 (FSDS-DAO #13) 对于 HSDD 女性的有效性证据充其量是有疑问的。我们没有发现 RECONNECT 试验先前发表的分类治疗反应结果的有效性证据。应报告所有疗效结果，但结果来自 11 项临床试验中的 8 项。政府规定的疗效结果迄今尚未公布（包括 FSDS-DAO 总分、FSFI 总分、FSFI 觉醒领域和女性性遭遇概况-修订版中的项目）。我们分析了这些结果，其影响大小从零到很小不等。其他几个连续和明确的结果产生了适度的明显好处，尽管几乎所有这些结果都可能是事后得出的。纵观之前两篇出版物和当前研究的 RECONNECT 试验数据，bremelanotide 的益处在统计学上是适度的，并且仅限于在患有 HSDD 的女性中存在有效性证据不足的结果。其他几个连续和明确的结果产生了适度的明显好处，尽管几乎所有这些结果都可能是事后得出的。纵观之前两篇出版物和当前研究的 RECONNECT 试验数据，bremelanotide 的益处在统计学上是适度的，并且仅限于在患有 HSDD 的女性中存在有效性证据不足的结果。其他几个连续和明确的结果产生了适度的明显好处，尽管几乎所有这些结果都可能是事后得出的。纵观之前两篇出版物和当前研究的 RECONNECT 试验数据，bremelanotide 的益处在统计学上是适度的，并且仅限于在患有 HSDD 的女性中存在有效性证据不足的结果。