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Multilevel analyses of on-demand medication data, with an application to the treatment of Female Sexual Interest/Arousal Disorder.

ABSTRACT: Data from clinical trials investigating on-demand medication often consist of an intentionally varying number of measurements per patient. These measurements are often observations of discrete events of when the medication was taken, including for example data on symptom severity. In addition to the varying number of observations between patients, the data have another important feature: they are characterized by a hierarchical structure in which the events are nested within patients. Traditionally, the observed events of patients are aggregated into means and subsequently analyzed using, for example, a repeated measures ANOVA. This procedure has drawbacks. One drawback is that these patient means have different standard errors, first, because the variance of the underlying events differs between patients and second, because the number of events per patient differs. In this paper, we argue that such data should be analyzed by applying a multilevel analysis using the individual observed events as separate nested observations. Such a multilevel approach handles this drawback and it also enables the examination of varying drug effects across patients by estimating random effects. We show how multilevel analyses can be applied to on-demand medication data from a clinical trial investigating the efficacy of a drug for women with low sexual desire. We also explore linear and quadratic time effects that can only be performed when the individual events are considered as separate observations and we discuss several important statistical topics relevant for multilevel modeling. Taken together, the use of a multilevel approach considering events as nested observations in these types of data is advocated as it is more valid and provides more information than other (traditional) methods.

SUBMITTER: Kessels R

PROVIDER: S-EPMC6695215 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Multilevel analyses of on-demand medication data, with an application to the treatment of Female Sexual Interest/Arousal Disorder.

Kessels Rob R Bloemers Jos J Tuiten Adriaan A van der Heijden Peter G M PGM

PloS one 20190815 8

Data from clinical trials investigating on-demand medication often consist of an intentionally varying number of measurements per patient. These measurements are often observations of discrete events of when the medication was taken, including for example data on symptom severity. In addition to the varying number of observations between patients, the data have another important feature: they are characterized by a hierarchical structure in which the events are nested within patients. Traditiona ...[more]

PMID: 31415608

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Project description:BackgroundModels depicting sexual desire as responsive to sexual arousal may be particularly apt for women experiencing arousal or desire difficulties, and the degree to which arousal triggers desire may depend on the relationship context and desire target and timing-yet, these associations have not been directly tested among women with and without sexual interest/arousal disorder (SIAD).AimTo assess the role of SIAD status and relationship satisfaction in the associations between genital arousal and 4 types of responsive desire.MethodsOne hundred women (n = 27 meeting diagnostic criteria for SIAD) in romantic relationships with men viewed a sexual film (pleasurable intimate depiction of oral sex and penile-vaginal intercourse) while their genital arousal was recorded via vaginal photoplethysmography (n = 63) or thermal imaging of the labia (n = 37). Partner and solitary desire was assessed immediately before and after the film (immediate desire) and 3 days later (delayed desire).OutcomesOutcomes consisted of genital response (z scored by method) and associations between genital response and responsive sexual desire.ResultsThe key difference between women with and without SIAD was not in their ability to experience genital arousal but in how their genital responses translated to responsive sexual desire. Women with SIAD actually exhibited greater genital arousal than unaffected women. Associations between genital arousal and desire were significant only for women with SIAD and depended on relationship satisfaction and desire type. For women with SIAD with low relationship satisfaction, higher arousal predicted lower immediate desire for a partner; for those with high relationship satisfaction, arousal was either positively related (vaginal photoplethysmography) or unrelated (thermal imaging of the labia) to immediate desire for a partner. Associations with other desire types were not significant.Clinical implicationsPatterns of genital arousal and partner-specific responsive desire among women affected with SIAD were indicative of an avoidance model in response to heightened genital arousal, unless relationship satisfaction was high; attending to genital arousal sensations could be a means of triggering sexual desire for women with SIAD who are satisfied in their relationships.Strengths and limitationsThis is one of the first sexual psychophysiologic studies to connect relationship factors to patterns of sexual response. The differing arousal assessment procedures and lack of official diagnosis may have attenuated results. The homogeneous sample and in-person session requirement limit generalizability.ConclusionWhen compared with unaffected women, women affected by SIAD may exhibit stronger arousal responses with sufficiently incentivized sexual stimuli, and the connection between their genital arousal and responsive desire for their partners may be stronger and more dependent on relationship context.

Project description:IntroductionFemale Genital Sexual Arousal Disorder (FGSAD) seriously affects women's quality of life and Sexual life, but it still lacks ideal FGSAD animal models for further study.AimTo establish a specific model of female genital sexual arousal disorder and explore the mechanisms resulting in FGSAD.MethodsAfter delivery, female rats were guided by expansions of the vagina and ovariectomy (VD+OVX, n = 10); in VD group female rats were just extended by the vagina (VD, n = 10), in OVX group female rats were treated with ovariectomy (OVX, n = 10);the remaining had 1 longitudinal incision as sham group(n = 10).OutcomesVaginal dilatation combined with ovariectomy in rats may reflect female genital sexual arousal disorder with high reproducibility and stability.ResultsVaginal tissue of female rats in OVX group and VD+OVX group showed an increase in blood flow, decrease in muscle content compared to the sham group. The proportion of collagen fiber I/III decreased and the elastic fiber showed significant rupture and fragmentation; Structural reticular integrity was also significantly separated and broken from the muscle fibers. However, there was no significant difference in vaginal blood flow, fibers and vascular between VD group and Sham group. The damage of vaginal tissue in VD+OVX group was more significant than that in OVX and VD groups.Clinical translationWe have constructed a specific animal model that can provide clinical insights into the mechanism of FGSAD and serves as a good avenue for further research of its treatment.Strengths and limitationsVaginal dilatation combined with ovariectomy in rats is a specific animal model with high reproducibility and stability, but we do acknowledge the shortcomings and limitation present in our study. Since genital arousal disorder has many different etiologies that impact the vagina, the clitoris and surrounding tissues, there is no "gold standard" model that different models attempt to investigate different etiologies.ConclusionThe female genital sexual arousal disorder model established by vaginal dilatation combined with ovariectomy is a novel rat model with simple induction conditions, which pathogenic mechanism of female genital sexual arousal disorders maybe connected with the change of VEGF and MMP-9 in vaginal fibromuscular system and microvascular. Li G, Yu P, Hu Y, et al. Establishment of Rat Model of Female Genital Sexual Arousal Disorder. Sex Med 2022;10:100530.

Project description:Attempts to develop a drug treatment for female sexual interest/arousal disorder have so far been guided by the principle of 'one size fits all', and have failed to acknowledge the complexity of female sexuality. Guided by personalized medicine, we designed two on-demand drugs targeting two distinct hypothesized causal mechanisms for this sexual disorder. The objective of this study was to design and test a novel procedure, based on genotyping, that predicts which of the two on-demand drugs will yield a positive treatment response. In a double-blind, randomized, placebo-controlled cross-over experiment, 139 women with female sexual interest/arousal disorder received three different on-demand drug-combination treatments during three 2-week periods: testosterone 0.5 mg + sildenafil 50 mg, testosterone 0.5 mg + buspirone 10 mg, and matching placebo. The primary endpoint was change in satisfactory sexual events. Subjects' genetic profile was assessed using a microarray chip that measures 300,000 single-nucleotide polymorphisms. A preselection of single-nucleotide polymorphisms associated with genes that are shown to be involved in sexual behaviour were combined into a Phenotype Prediction Score. The Phenotype Prediction Score demarcation formula was developed and subsequently validated on separate data sets. Prediction of drug-responders with the Phenotype Prediction Score demarcation formula gave large effect sizes (d = 0.66 through 1.06) in the true drug-responders, and medium effect sizes (d = 0.51 and d = 0.47) in all patients (including identified double, and non-responders). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the Phenotype Prediction Score demarcation formula were all between 0.78 and 0.79, and thus sufficient. The resulting Phenotype Prediction Score was validated and shown to effectively and reliably predict which women would benefit from which on-demand drug, and could therefore also be useful in clinical practice, as a companion diagnostic establishing the way to a true personalized medicine approach.

Project description:BackgroundFor the treatment of female sexual dysfunction, the most relevant outcome measures are patient-reported treatment effects and changes in symptoms, underscoring the need for reliable, validated patient-reported outcome (PRO) instruments. The aim of this study was to evaluate the psychometric characteristics (validity and reliability) of the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) PRO measure, which was adapted from the validated FSDS-Revised (FSDS-R) questionnaire and added 2 questions involving arousal and orgasm.MethodsPsychometric analyses were based on the data from a multicenter phase 2b dose-finding study that compared the safety and efficacy of bremelanotide versus placebo and were conducted in the evaluable modified intent-to-treat population (N = 325) from that study. Psychometric evaluation of the new items in the FSDS-DAO included confirmatory factor analyses, tests of internal consistency and test-retest reliability, examinations of convergent and discriminant validity, and determination of responsiveness. The validity of the FSDS-DAO was evaluated based on previously developed instruments, including the Female Sexual Function Index (FSFI), General Assessment Questionnaire (GAQ), Women's Inventory of Treatment Satisfaction (WITS-9), and Female Sexual Encounter Profile-Revised (FSEP-R).ResultsConfirmatory factor analyses demonstrated that the FSDS-DAO items fit very well (Bentler's comparative fit index of 0.929). Cronbach's α for the FSDS-DAO total score was ≥ 0.91 at Visits 1, 2, 5, and 12, demonstrating adequate internal consistency reliability. Test-retest reliability was acceptable with an intra-class coefficient of 0.61 and a Spearman's correlation coefficient score of 0.62 between Visits 1 and 2 (4 weeks). Acceptable construct validity was demonstrated by significant correlations with related PRO scales in the expected directions and magnitude. For example, participants reporting the worst levels of sexual function on the FSFI also showed the worst FSDS-DAO scores at Visits 5 and 12. The FSDS-DAO total score was responsive to change.ConclusionsEvidence supports the validity and reliability of the FSDS-DAO for assessing sexually related distress in women with female sexual arousal disorder and/or hypoactive sexual desire disorder; the addition of the arousal and orgasm items did not impact the validity and reliability of the measure. Clinical Trial Registration ClinicalTrials.gov NCT01382719.

Project description:Very little has been elucidated about sexual interest in female-to-male (FtM) transsexual persons.To investigate the sexual interest of FtM transsexual persons vs that of men using an eye-tracking system.The study included 15 men and 13 FtM transsexual subjects who viewed three sexual videos (clip 1: sexy clothed young woman kissing the region of the male genitals covered by underwear; clip 2: naked actor and actress kissing and touching each other; and clip 3: heterosexual intercourse between a naked actor and actress) in which several regions were designated for eye-gaze analysis in each frame. The designation of each region was not visible to the participants.Visual attention was measured across each designated region according to gaze duration.For clip 1, there was a statistically significant sex difference in the viewing pattern between men and FtM transsexual subjects. Longest gaze time was for the eyes of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. For clip 2, there also was a statistically significant sex difference. Longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects, and there was a significant difference between regions with longest gaze time. The most apparent difference was in the gaze time for the body of the actor: the percentage of time spent gazing at the body of the actor was 8.35% in FtM transsexual subjects, whereas it was only 0.03% in men. For clip 3, there were no statistically significant differences in viewing patterns between men and FtM transsexual subjects, although longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects.We suggest that the characteristics of sexual interest of FtM transsexual persons are not the same as those of biological men. Tsujimura A, Kiuchi H, Soda T, et al. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study. Sex Med 2017;5:e169-e174.

Dataset Information

Multilevel analyses of on-demand medication data, with an application to the treatment of Female Sexual Interest/Arousal Disorder.

Publications

Multilevel analyses of on-demand medication data, with an application to the treatment of Female Sexual Interest/Arousal Disorder.

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