Robert Pyke

Reliability and Validity of the Sexual Interest and Desire Inventory–Female (SIDI-F), a Scale Designed to Measure Severity of Female Hypoactive Sexual Desire Disorder

The Sexual Interest and Desire Inventory–Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to quantify the severity of symptoms in women diagnosed with hypoactive sexual desire disorder (HSDD). The present investigation assessed the reliability and validity of the SIDI-F as a measure of HSDD severity. Results show that the SIDI-F exhibits excellent internal consistency, with Cronbachs alpha of 0.9. The validity of the SIDI-F as a measure of HSDD severity was confirmed by a number of observations. Women with a clinical diagnosis (Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR; American Psychiatric Association, 2000]) of HSDD had significantly lower SIDI-F scores than women not meeting diagnostic criteria for any subtype of female sexual dysfunction and women diagnosed with female orgasmic disorder. There was a high correlation between scores on the SIDI-F and scores on the Female Sexual Function Index (FSFI; Rosen et al., 2000) and an interactive voice response version of the Changes in Sexual Functioning Questionnaire (CSFQ; Clayton, McGarvey, & Clavet, 1997; Clayton, McGarvey, Clavet, & Piazza, 1997), two validated measures that assess general female sexual dysfunction. In contrast, there was a poor correlation between SIDI-F scores and scores on a slightly modified Marital Adjustment Scale (Locke, Wallace, 1959; MAS), an assessment of general (nonsexual) relationship satisfaction. Taken together, the results of the present investigation indicate that the SIDI-F is a reliable and valid measure of HSDD severity, independent of relationship issues.

Psychological Treatment Trials for Hypoactive Sexual Desire Disorder: A Sexual Medicine Critique and Perspective.

INTRODUCTION Publications claim efficacy for treatment of hypoactive sexual desire disorder (HSDD) in women with cognitive behavior therapy (CBT) and mindfulness meditation training (MMT). However, no review has evaluated the evidence for these therapies from the rigorous perspective of sexual medicine. AIMS The aim of this study was to evaluate the published controlled trials of CBT and MMT for disorders of sexual desire from the perspective of sexual medicine standards of control paradigms, risk/benefit ratios, and clinical significance. METHODS MEDLINE was reviewed from the last 10 years. Evaluated study quality via 10 metrics and efficacy as mean change, and proportion of responders and remitters. RESULTS Three controlled trials support CBT and two controlled trials support MMT. The reports of the trials each lacked several scientific requirements: a hierarchy of endpoints with a planned primary endpoint, sufficient information on the intervention to reproduce it, randomization, adequate control, accepted measures of benefits and harms, compliance data, and/or outcomes of clinical relevance. CONCLUSIONS Psychological treatments for HSDD are not yet supported by adequate clinical trials. The current scientific and regulatory standards for drug treatment trials should also be applicable to psychological treatment trials.

Validation of the Sexual Interest and Desire Inventory-Female in Hypoactive Sexual Desire Disorder

INTRODUCTION The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to measure hypoactive sexual desire disorder (HSDD) severity in women. AIM To estimate the reliability and validity of the SIDI-F as a measure of HSDD severity. METHODS Women, aged 18-65 years, with primary HSDD, Female Sexual Arousal Disorder (FSAD), or no Female Sexual Dysfunction (no FSD) participated in two nontreatment studies (in North America and Europe). On days 0 and 28, subjects were assessed using the SIDI-F, Female Sexual Function Index (FSFI), Changes in Sexual Functioning Questionnaire-Female (CSFQ-F), Locke-Wallace Marital Adjustment Test (MAT) and the Female Sexual Distress Scale (FSDS). MAIN OUTCOME MEASURES Discriminant validity, convergent validity, divergent validity, test-retest validity, and internal consistency of the SIDI-F. RESULTS The North American study enrolled women with HSDD (N = 113), FSAD (N = 49) and no FSD (N = 61); the European study enrolled women with HSDD (N = 130) and no FSD (N = 124). In both studies, mean SIDI-F total score for women with HSDD was lower than for those with no FSD (P < 0.001, for all) demonstrating discriminant validity. Further, mean SIDI-F total score for women with HSDD was lower than for those with FSAD in the North American study (P < 0.001). Convergent validity with the FSFI and CSFQ-F and divergent validity with MAT were demonstrated. Test-retest reliability and internal consistency were high. CONCLUSIONS The SIDI-F is a valid and reliable measure of HSDD severity in women.

Validity of the Decreased Sexual Desire Screener for Diagnosing Hypoactive Sexual Desire Disorder

The Decreased Sexual Desire Screener is a brief diagnostic instrument for generalized acquired Hypoactive Sexual Desire Disorder in women. During the screening visit of 2 clinical trials, the authors assessed sensitivity of the Decreased Sexual Desire Screener in premenopausal women presenting with decreased sexual desire. The authors compared diagnoses of generalized acquired Hypoactive Sexual Desire Disorder made by clinicians who were not trained or specialized in the diagnosis of female sexual dysfunction using the Decreased Sexual Desire Screener with diagnoses made by expert clinicians after an extensive diagnostic interview. The sensitivity of the Decreased Sexual Desire Screener was 0.946 in a North American trial and 0.960 in a European trial.

Cutoff Score of the Sexual Interest and Desire Inventory-Female for Diagnosis of Hypoactive Sexual Desire Disorder

OBJECTIVE To determine the most appropriate cutoff value for the Sexual Interest and Desire Inventory-Female (SIDI-F) score to discriminate between women with hypoactive sexual desire disorder (HSDD) and those with no female sexual dysfunction (FSD). The SIDI-F is a clinician-rated instrument consisting of 13 items designed to assess HSDD severity in women. The total score ranges from 0 to 51, with higher scores indicating better sexual function. METHODS Data from patients enrolled in a North American nontreatment study and a European nontreatment study were analyzed. Both studies were 4-week, prospective, multicenter trials designed to assess the reliability and validity of the SIDI-F. Only patients with HSDD or no FSD were included in this analysis. Receiver operating characteristics (ROC) analysis was used to determine the ability of the SIDI-F to differentiate between patients with HSDD and those with no FSD at baseline. RESULTS A total of 428 women were included in this analysis: 174 from North America (HSDD 113, no FSD 61) and 254 from Europe (HSDD 130, no FSD 124). In the North American study, a SIDI-F cutoff score of 33 minimized the difference between sensitivity (94.7%) and specificity (93.4%). In the European study, SIDI-F cutoff scores of both 33 and 34 minimized the difference between sensitivity (95.2%) and specificity (94.4%). CONCLUSIONS In appropriately screened women, a SIDI-F score of ≤33 indicates the presence of HSDD.

Standards for Clinical Trials in Male and Female Sexual Dysfunction: II. Patient-Reported Outcome Measures

The second article in this series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, focuses on measurement of patient-reported outcomes (PROs). Together with the design of appropriate phase I to phase IV clinical trials, the development, validation, choice, and implementation of valid PRO measurements-the focus of the present article-form the foundation of research on treatments for male and female sexual dysfunctions. PRO measurements are assessments of any aspect of a patients health status that come directly from the patient (ie, without the interpretation of the patients responses by a physician or anyone else). PROs are essential for assessing male and female sexual dysfunction and treatment response, including symptom frequency and severity, personal distress, satisfaction, and other measurements of sexual and general health-related quality of life. Although there are some relatively objective measurements of sexual dysfunction (ie, intravaginal ejaculatory latency time, frequency of sexual activity, etc), these measurements do not comprehensively assess the occurrence and extent of sexual dysfunction or treatment on the patients symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patients perspective.

Standards for Clinical Trials in Male and Female Sexual Dysfunction: III. Unique Aspects of Clinical Trials in Male Sexual Dysfunction

This series of articles, Standards for Clinical Trials in Male and Female Sexual Dysfunction, began with the discussion of a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for the selection of study population and study duration in male and female sexual dysfunction. The second article in this series discussed fundamental principles in development, validation, and selection of patient- (and partner-) reported outcome assessment. The third and present article in this series discusses selected aspects of sexual dysfunction that are that are unique to male sexual dysfunctions and relevant to the conduct of clinical trials of candidate treatments for men.

What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder

Introduction Counts of satisfying sexual events (SSEs) per month have been criticized as an end point in treatment trials of women with hypoactive sexual desire disorder (HSDD) but grounding improvement in sexual desire by assessing changes in sexual behavior remains of some importance. Methods We conducted a literature review to find validated measurements that are specific sexual behavioral correlates of low sexual desire. We compared expert-proposed criteria for dysfunctional desire, expert-developed sets of scale items, and self-rated scales developed before issuance of, or in accordance with, the Food and Drug Administration’s guidance on developing patient-reported outcomes. Behavioral measurements of HSDD were isolated from these sets of criteria or scales. Main Outcome Measures We outline a plan to evaluate such behavioral measurements of HSDD with reference to SSEs. Results Eleven rating scales, four expert-originated and seven self-rated scales mainly derived from patient input were identified as well validated and relevant to HSDD. Three recent sets of diagnostic criteria for conditions such as HSDD were compared with the scales. Twenty-four different symptoms were found in the scales. Content found relevant to HSDD during development of the rating scales varied highly among measurements, including the self-rated scales developed in conformity with current recommendations for patient-reported outcome measurements. The only item on all sets was desire for sexual activity. Four other items were in approximately at least half the sets: sexual thoughts or fantasies, frequency of sexual activity, receptivity, and initiations. Sexual thoughts or fantasies were in every expert-derived set but in only three of the seven patient-derived sets. Receptivity was in five of the seven expert-derived sets vs two of the seven patient-derived sets. Frequency of sexual activity was in one of the seven expert-derived sets but in five of the patient-derived sets. Initiation was in approximately half the two sets. All other items were on one to three sets each. We identified three sexual behaviors of validated specificity for female HSDD: frequency of sexual activity, receptivity, and initiations. Six or seven items are relevant and informative. The item on frequency of sexual activity in the Changes in Sexual Functioning–Female scale is the only item that covers frequency of dyadic and solitary sexual activity. An item in the Female Sexual Desire Questionnaire (FSDQ) covers the intuitively relevant topic of frequency of sexual activity motivated by the woman’s desire. Three FSDQ items on initiations and two items on receptivity reflect expert opinion on the sexual behaviors of most relevance to HSDD, but the FSDQ has not been validated in women with HSDD. Conclusions SSEs have been discredited as the primary measurement in clinical trials of women with HSDD, but it would be meaningful to include at least one sexual behavioral symptom specific to HSDD as an end point. Expert-recommended sexual behaviors specifically related to HSDD are irregularly represented in self-rating scales whether developed as in the Food and Drug Administration guidance on patient-reported outcomes or not. Six or seven items on sexual behavior in self-rated scales can be recommended for relevance to women with HSDD in clinical trials. Items on female sexual behavior should be tested in comparison with SSEs in women with HSDD for relevance and for treatment sensitivity, and responder and functional and dysfunctional cutoffs should be determined before incorporation into large-scale clinical trials. Pyke R and Clayton A. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder. Sex Med 2017;5:e73–e83.

Is Flibanserin Meaningfully Superior to Placebo

We acknowledge a recent critique by Balon and Segraves (2017) of the efficacy of psychotherapy and of flibanserin for treating hypoactive sexual desire disorder (HSDD). Two points need to be addressed further than we already have (Pyke & Clayton, 2015). One point relates to their onesentence summary, and skeptical question, about the superiority of flibanserin over placebo: “Is one-half additional satisfying sexual events per month clinically significant?” Satisfying sexual events (SSE) has been roundly criticized as an inappropriate measure in HSDD (for a summary, see Kingsberg & Althof, 2011) because it is not part of the disorder’s definition, it is poorly correlated with the definitional constructs of HSDD (loss of sexual desire and distress related to that loss), it has high placebo response, and, as a count of events, it lacks the needed psychometric properties of a valid measure (Food and Drug Administration [FDA], 2014). Worse, its distribution is highly right-skewed (in the flibanserin Phase 3 trials, baseline values varied from 0 to over 30 yet the mean was about 1.5), so the only appropriate statistical analysis is nonparametric, an argument of Boehringer Ingelheim (the original sponsor of the drug) that was accepted by the FDA (FDA, 2010). For SSE, the extreme variation from a normal distribution is poorly captured by using a mean and a standard deviation as expressions of central tendency and variance. Thus, statistics on effect size, such as Cohen’s d, are invalid as expressions of the magnitude of superiority of drug over placebo for this measure. On the other hand, on validated endpoints of the two constructs relevant to HSDD (sexual desire and related sexual distress), the change with drug or placebo from baseline to end of treatment can be used to provide valid information about effect size of treatments. Using baseline standard deviation and mean change in the three flibanserin Phase 3 trials (Table 1), we calculated effect size as Cohen’s d. Values from 0.2 to 0.4 can be designated as small, values 0.5 to 0.7 as moderate, and values of 0.8 or more as large (Cohen, 1992). Pill placebo treatment for 24 weeks was associated with moderate to large treatment effect sizes, namely 0.5 to 1.0 (median of the six values, 0.80). Drug treatment was associated with large effect sizes, from 0.83 to 1.43 (median, 1.16). Drug-placebo differences in effect size were 0.31 to 0.50, with a median of 0.43, showing a small-to-moderate differential effect size. Thus, it is not only statistical significance (arguably based as much on a large sample size as on clinically

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical trial design for women.