Re-Analyzing Phase III Bremelanotide Trials for “Hypoactive Sexual Desire Disorder” in Women

Abstract

Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My metaanalysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.

Irrelevancies and Inaccuracies Miss the Target: A Response to Kingsberg et al.

“…Psychology, Metropolitan State University I was disappointed by the response of Kingsberg et al (2021), who failed to seriously engage with the most pressing concerns raised in my re-analysis (Spielmans, 2021). Kingsberg et al (2021)'s commentary included irrelevant statements, inadequate or inaccurate arguments, unsubstantiated concerns regarding my level of knowledge, and mischaracterizations of my re-analysis.…”

“…Table 1 shows the main concerns originally listed in table 1 of my re-analysis (Spielmans, 2021) alongside Kingsberg et al's (2021) response (if any), followed by summaries of my rebuttals to Kingsberg et al's responses. Kingsberg et al responded, more or less directly, to four of my 10 main concerns.…”

“…In any case, readers can rest assured that I am quite aware of Revicki et al (2018). In fact, I cited and discussed it in my re-analysis (Spielmans, 2021). Revicki et al (2018) derived cutoff scores for only the FSFI-D and FSDS-DAO #13, not the bevy of other categorical outcomes reported by Kingsberg et al (2019).…”

“…They stated that I may not understand the pernicious effects of untreated HSDD on individuals and relationships, citing no sources to support these claims. The phase III trials provided Main concern raised in Spielmans et al (2021) Response by Kingsberg et al (2021) My response to Kingsberg et al (2021) Most protocol-specified outcomes are unreported ". .…”

Corrigendum Supports Therapeutic Contribution of Acupoint Tapping to EFTs' Observed Effects

“…As shown by Spielmans et al (Spielmans, 2012(Spielmans, , 2021a(Spielmans, , 2021bSpielmans et al, 2010) and Del Re et al ( 2013) and Allen et al (2012), a primary focus of Spielmans's academic career has been reanalyses, meta-analyses, and critiques of the work of other investigators, as opposed to conducting and publishing his own original research. Primary research might take advantage of Spielmans's considerable statistical talents and advance science in meaningful ways.…”