Establishing the content validity of the confidence in performing sexual intercourse and difficulty in performing sexual intercourse questionnaires

Transcription

1 International Journal of Impotence Research (2013) 25, & 2013 Macmillan Publishers Limited All rights reserved /13 ORIGINAL ARTICLE Establishing the content validity of the confidence in performing sexual and difficulty in performing sexual questionnaires RP Hayes 1, J Henne 2, ML Meldahl 1 and A Sontag 3 The aim of this qualitative analysis was to establish the content validity of two new patient-reported outcome (PRO) measures, Confidence in Performing Sexual Intercourse Questionnaire (CPSIQ) and Difficulty in Performing Sexual Intercourse Questionnaire (DPSIQ). Six separate qualitative studies (interviews/focus groups) were conducted from December 2009 to August 2010 by a single moderator and included 227 men with erectile dysfunction (ED; mean age: 54 years, 58% Caucasian). In the first three studies, concepts about ED and its treatment that were important and relevant to men with ED were identified. They included: getting and controlling ; hardness; maintaining for desired duration; achieving and controlling ejaculation; satisfying partner; changing sexual positions; and frequency and spontaneity of sexual. In the subsequent two studies, concepts were confirmed and transformed into CPSIQ and DPSIQ items. The last study entailed a cognitive interview of the CPSIQ and DPSIQ to ensure that respondents interpretation of the PRO items were consistent with their intended meaning and that both recall periods and response sets were acceptable. After psychometric testing, the CPSIQ and DPSIQ could serve as complementary tools to existing PROs used in ED clinical trials. International Journal of Impotence Research (2013) 25, ; doi: /ijir ; published online 2 May 2013 Keywords: confidence; difficulty; erectile dysfunction; sexual INTRODUCTION Erectile dysfunction (ED) is a complex and multidimensional condition associated with psychological and relationship concerns, including decreased quality of life, self-esteem and interpersonal relationship problems. 1 3 A man s expectation of difficulty and his associated level of confidence (that is, selfefficacy) in his ability to achieve and maintain adequate s for sexual intercrouse significantly impacts sexual performance. 4 5 There are existing instruments that assess confidence and/or difficulty in performing sexual but most include these concepts as a subdomain of a multi-domain instrument (for example, Self-Esteem And Relationship questionnaire, 6 Psychological and Interpersonal Relationship Scale 7 ) or single items as in the the Erectile Function Domain of the International Index of Erectile Functioning-Erectile Function Domain (IIEF-EF). 8 To our knowledge, few, if any, instruments have been developed that are dedicated solely to the assessment of confidence in or difficulty performing sexual. Moreover, most of the existing instruments, while demonstrating evidence of reliability and validity, are missing evidence of the level of patient input in item development required to establish content validity. In 2009, the Food and Drug Administration (FDA) published a guidance to industry on the development of patient-reported outcome (PRO) measures to support product labeling. 9 In this guidance, the agency places strong emphasis on the establishment of content validity and stresses that PRO item content must be developed with patient input and then be evaluated by patients in terms of comprehensiveness and interpretability. 10 Therefore, the overall goal of this study was to establish the content validity of two new PRO instruments, one that assesses the level of confidence men with ED have in performing aspects of sexual and one that assesses the level of difficulty men with ED have in performing sexual. The intent of these measures is to complement existing accepted ED measures while also meeting current FDA standards for PRO measure development. MATERIALS AND METHODS Six separate qualitative studies were conducted from December 2009 to August The objective of the first three studies was concept elicitation (that is, open-ended questioning to elicit concepts related to experiencing ED and its treatment), the objective of the next two studies was to confirm that the concepts elicited in the first three studies were also relevant and important in samples of men with ED and specified characteristics (for example, comorbidities). The objective of the sixth study was cognitive interviewing (that is, testing for understanding and interpretability) of items generated for the two proposed measures, the Confidence in Performing Sexual Intercourse Questionnaire (CPSIQ) and the Difficulty in Performing Sexual Intercourse Questionnaire (DPSIQ). Each of the six studies was conducted in at least two large cities in the United States (US), including Atlanta, Georgia; Boston, Massachusetts; Chicago, Illinois; Hollywood, Florida; Houston, Texas; Los Angeles, California; New York, New York; Philadelphia, Pennsylvannia; Phoenix, Arizona; and San Francisco, California (Table 1). Study participants Participants in all the studies were required to be 421 years of age, heterosexual and report having a regular sexual partner. Efforts were made 1 Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2 The Henne Group, San Francisco, CA, USA and 3 Lilly USA, LLC, Indianapolis, IN, USA. Correspondence: Dr RP Hayes, Global Health Outcomes, Eli Lilly and Company, Lilly Corporate Center, Drop Code 1730, Indianapolis, IN 46285, USA. hayes_clarice@lilly.com Received 9 December 2012; revised 22 March 2013; accepted 4 April 2013; published online 2 May 2013

2 Table 1. Objective, sites, qualitative method, purposive sampling and primary topics of discussion across six qualitative studies 235 Study Objectives Method Sites (methodology) Purposive sampling 1 In a sample of men with ED currently using PDE5 inhibitors, identify topic areas related to the experience of and treatment for ED 2 In a sample of men with ED (including men naive to treatment with PDE5 inhibitors) continue to identify and refine domains and concepts related to the experience of and treatment for ED 3 In a sample of men with ED (including men naive to treatment with PDE5 inhibitors), assess the extent to which saturation was achieved in the identification of domains and concepts related to the experience of and treatment for ED 4 In a sample of men who are incomplete responders to PDE5 inhibitors, confirm saturation in the idenfication of domains and concepts related to the experience of and treatment for ED 5 In a sample of men with ED and comorbid conditions (for example, diabetes, heart disease), confirm saturation in the idenfication of domains and concepts related to the experience of and treatment for ED 6 In a sample of men with ED, test items developed for an assessment of 1) confidence in performing sexual (that is, CPSIQ) and 2) difficulty in performing sexual ( that is, DPSIQ) 18 IDIs 3FGs 24 IDIs 4FGs 3 US cities: Atlanta, GA; Chigago, IL; Los Angeles, CA (6 IDIs and 1 FG per city) 4 US cities: Hollywood, FL; Los Angeles, CA; New York, NY; Phoenix, Az (6 IDIs and 1 FG per city) 40 IDIs 6 US cities: Boston, MA; Chigago, IL; Houston, TX; Los Angeles, CA; New York, NY; Philadelphia, PA (4 7 IDIs per city) All participants: Currently using a PDE5 inhibitor for ED IDI participants Naive to PDE5 inhibitor treatment and IIEF-EF score o26 of ED FG participants 1 FG naive to PDE5 inhibitor 3 FG currently using a PDE5 inhibitor for treatment of ED IDI participants Naive to PDE5 inhibitor treatment and IIEF-EF score o26 of ED IIEF- EF scores 426 in last month when using PDE-5 inhibitors (responder) 33 IDIs 6 US cities: (4 7 IDIs per city) IDI participants Currently using PDE5 inhibitors with IIEF-EF scoreso26 in last month when using PDE-5 inhibitors for treatment of ED (incomplete responder) 4 FGs 2 US cities: Houston, TX; New York, NY (2 FGs per city) 24 cognitive interviews (CIs) 3 US cities: Houston, TX; New York, NY; San Francisco, CA (8 CIs per city) FG participants of men with ED and comorbidities (eg diabetes, heart disease) Naive to PDE5 inhibitor treatment and IIEF-EF scoreo26 of ED CI participants of men with ED and comorbidities (eg, diabetes, heart disease) Naive to PDE5 inhibitor treatment and IIEF-EF scoreo26 of ED Abbreviations: AZ, Arizona; CA, California; CI, cognitive interview; ED, erectile dysfunction; FG, focus group; FL, Florida; IDI, indepth interview; IL, Illinois; IIEF-EF, International Index of Erectile Functioning-Erectile Function Domain; MA, Massachusetts; NY, New York; PA, Pennsylvannia; TX, Texas. to recruit participants who were diverse in race/ethnicity and geographical location. For each study, purposive sampling dictated ED severity and PDE5 inhibitor treatment experience (PDE5 inhibitor user (used at least eight times in the past year) or PDE5 inhibitor treatment naive). An IIEF-EF score o26 was required for participants who were PDE5 treatment naive or not currently using any other physician-prescribed ED treatment (for example, vacuum constriction device). Participants for all the six studies were recruited primarily through newspaper or internet advertisements and physician referrals. Men who showed interest in participating in a study (by providing their contact information to the recruiting agency) were screened using a standard screener and then, if qualified for the study, were scheduled to meet the moderator at a market research facility, a facility equipped with audio-visual equipment and one-way mirrors for conducting qualitative research, in their cities. Participants who reported using PDE5 inhibitors were asked to bring proof of treatment in the form of a physician prescription or a medication container. If men reporting PDE5 inhibitor use were unable to demonstrate proof of treatment on the day of their scheduled interview or focus group, they were disqualified from the study. Institutional Review Board s approval was received from the Ethical and Independent Review Services. Procedure A common procedure was followed for all the six studies. The same moderator (author JH) conducted all focus groups (Studies 1, 2 and 5), individual in-depth interviews (Studies 1 4) and cognitive interviews (Study 6). Participants informed consent was obtained at the market research facility before their participation. In addition, the moderator, at the beginning of each interview/focus group informed the participants of the confidentiality of their responses and their right to refuse to respond to any of the interview/focus group questions and the potential of observation through video streaming (without archiving) by the study sponsor. For concept elicitation (Studies 1 3) and confirmation (Studies 4 and 5), the moderator used a semi-structured discussion guide, which began with a discussion of the men s history and experiences with ED. The moderator asked PDE5 inhibitor users about their treatment history and perceived treatment effects, whereas he asked PDE5 inhibitor treatment-naive participants about why they had not sought treatment and their expectations about benefits/risks of PDE5 inhibitor treatment. The interviews were scheduled to last 1 h and the focus groups 2 h. For cognitive interviewing (Study 6), the moderator used a semistructured interview guide to elicit the following from participants about items generated for the two draft PRO measures: (1) interpretation of items; (2) understanding of response scales; (3) interpretation of recall periods; (4) understanding of general instructions; (5) comments about the format, length and general content of the questionnaire; and (6) suggestions for additional items. Data analysis For the concept elicitation/confirmation studies (Studies 1 5), audiofiles were transcribed and content analysis was conducted based on grounded theory Coders preliminarily reviewed the transcriptions and moderator field notes to identify broad topic areas (domains). To identify concepts, two coders (independent of the authors and study sponsor) first read the transcripts and then tagged text corresponding to the topic areas to form a coding guide. This coding guide functioned as an initial organization of domains (that is, coding framework) on which to base the grouping of concept codes in subsequent studies. As transcripts were coded, the coding framework was adjusted as needed. In addition, for each study, the coders organized transcripts chronologically. By doing this, the coders could evaluate the extent to which saturation, or the point at which new concept identification diminishes over time, was achieved for each domain. 9 ATLAS.ti (ATLAS.ti Scientific Software GmbH, Berlin, Germany), a qualitative data management software, was used to facilitate coding. & 2013 Macmillan Publishers Limited International Journal of Impotence Research (2013),

3 236 The authors (RPH, MLM, JH) used the code book from the five concept elicitation/confirmation studies to hypothesize conceptual frameworks for both the CPSIQ and DPSIQ and subsequently develop a pool of items to correspond to the frameworks. For cognitive interviewing (Study 6), content analysis was performed by coding each transcript for text corresponding to the following six topic areas: (1) interpretation of the meaning of each item; (2) understanding the response scales; (3) interpretation of the recall periods; (4) understanding of general instructions for the questionnaire; (5) comments about the format, length and general content of the questionnaire; and (6) possible concepts to be added to the questionnaire. Summary statistics were calculated for participant demographics. RESULTS Study participants A total of 227 men participated in the six studies. Samples in the six qualitative studies differed as noted below and in Table 1, but as a whole, the majority of the 227 participants were middle aged (60% aged years), Caucasian (58%), currently using PDE5 inhibitors to treat their ED (83%) and had IIEF-EF score of X17 (70%) (Table 2). Concept elicitation Study 1 participants (n ¼ 40) were all current users of PDE5 inhibitors and the majority had mild ED. Analysis of the transcripts from Study 1 resulted in the identification of 36 concepts (that is, codes) related to the ED experience and its treatment, which were grouped into six topic areas (for example, Reactions to ED). Study 2 participants (n ¼ 53) were similar in mean age and IIEF-EF scores as Study 1 participants, but 17 (32%) of the participants were naive to PDE5 inhibitor treatment. Review and coding of the transcripts from Study 2 led to the refinement of the topic areas identified in Study 1 into seven domains and their respective codes: (1) Understanding ED (for example, Dealing with other medical problems caused ED ); (2) Emotional Impact of ED (for example, Lose confidence, self esteem ); (3) Social Impact of ED (for example, She thinks I am not attracted to her or cheating on her ); (4) Impact of ED on Sexual Function (for example, Avoiding sex ); (5) PDE5 inhibitor Impact on Social/Partner Relationships (for example, Improved relationship ); (6) PDE5 inhibitor Impact on Erections (for example, Maintain longer ); and 7) PDE5 inhibitor Impact on Sexual Functioning (for example, Sex lasts longer ). Because the majority of codes for the five domains had emerged during Study 1, the results suggested that saturation was approached for all but two domains, Understanding ED and Impact of ED on Sexual Function. About twothirds of the codes within Understanding ED and one-third of the codes within Impact of ED on Sexual Function were generated in Study 2 (Table 3). To achieve saturation in all the domains, Study 3 was conducted. Study 3 participants (n ¼ 40) were similar in mean age and IIEF-EF scores and included both PDE5 users and those who were treatment naive. Only two new codes emerged, 1 for Emotional Impact of ED and 1 for PDE5 inhibitor Impact on Erections, representing p6% of the total codes for those domains. Therefore, saturation was considered to have been achieved for all the seven domains. Concept confirmation Because new ED treatments, including new PDE5 inhibitors may target men who are incomplete responders to PDE5 inhibitors (defined in this study as men who, when treated with PDE5 inhibitors, fail to score 425 on the IIEF-EF), the objective of Study 4 was to confirm saturation of the seven domains in incomplete responders. Therefore, participants (n ¼ 33) were all PDE5 inhibitor users but had overall lower IIEF-EF scores than participants in Studies 1 3. For four of the domains, no new codes emerged. However, for Emotional Impact of ED, Social Impact of ED and PDE5 inhibitor Impact on Sexual Function, 1 2 new codes emerged. These represented 5, 12 and 5%, respectively, of codes generated for those domains. The number of domains in which new codes were identified suggests that saturation may be less complete for this group of men, yet, the new codes represented only 3% of the 116 codes identified throughout Studies 1 4. The objective of Study 5 was to confirm saturation in a sample of men similar in age and IIEF-EF scores to participants in Studies 1 3 with the exception that a greater effort was made to recruit men with ED and comorbid conditions, such as diabetes. Therefore, Study 5 participants (n ¼ 37) were similar in mean age and IIEF-EF scores to most of the participants in Study 1 3, but nearly one-third reported having diabetes as compared with less than one quarter of participants in Studies 1 3. New codes emerged in only one domain, PDE5 Inhibitor Impact on Sexual Function. The three codes that emerged in this domain represented 15% of the codes generated for that domain but only 3% of the total codes generated across the four previous studies. Item generation After review of the coding book for the five qualitative studies, 10 codes were identified within the domains of ED Impact on Sexual Function, PDE5 inhibitor Impact on Erections and PDE5 inhibitor Impact on Sexual Function on which to base item generation for an assessment of confidence in performing sexual (that is, CPSIQ). In addition, five of these codes were deemed appropriate for item generation for an assessment of difficulty in performing sexual (that is, DPSIQ). The concepts represented by these codes are presented in Table 4 along with quotes supporting their importance and relevance. In keeping with FDA PRO guidance recommendations, 9 the authors generated items with a recall period of currently for the CPSIQ items and last time attempted sexual for the DPSIQ items. In keeping with guidance for the development of instruments designed to be evaluative 13, the response set was a 7-point Likert-type scale for the CPSIQ items and a 5-point Likerttype scale for the DPSIQ items (Table 4). Cognitive interviewing Study 6 participants (n ¼ 24) were similar in mean age and IIEF-EF scores to Study 5 participants. Cognitive interviewing with these participants indicated that their interpretation of the CPSIQ and DPSIQ items were consistent with the intended meanings. However, for two of the DPSIQ items: (1) long sexually satisfy and (2) enough for sexual to last in duration as long as you and would like it to last, some participants stated that their perceived difficulty would be dependent on their partners reactions or desires and that these were hard to judge or vary by partner. Therefore, these two items were deleted for the DPSIQ. Cognitive interviewing also indicated that the instructions, recall periods of the two instruments and the CPSIQ 7-point response set and DPSIQ 5-point response set were easily understood and acceptable. Questions posed to participants about possible additions to the CPSIQ or DPSIQ items did not elicit new items. DISCUSSION The overall goal of this study was to establish content validity for two new PRO instruments, CPSIQ and DPSIQ. Establishing content validity is the essential first step in PRO instrument development. As stated in the FDA guidance, Testing other measurement properties will not replace or rectify problems with content validity. 9 The guidance further stresses the need to demonstrate International Journal of Impotence Research (2013), & 2013 Macmillan Publishers Limited

4 Table 2. Self-reported characteristics of men with ED participating in six qualitative studies 237 Self-reported characteristic Study 1 (N ¼ 40) Study 2 (N ¼ 53) Study 3 (N ¼ 40) Study 4 (N ¼ 33) Study 5 (N ¼ 37) Study 6 (N ¼ 24) Total (N ¼ 227) Age (mean (SD), years) 46.9 (10.5) 50.6 (11.5) 54.5 (8.8) 52.5 (10.7) 59.7 (4.5) 61.0 (4.8) 53.5 (10.3) Age groups (%) Race/ethnicity (%) European descent (Caucasian) African descent Latino descent Asian descent Mixed descent Comorbidities (%) High blood pressure High cholesterol Diabetes Chronic back pain Hernia Heart problems Cardiovascular disease Stroke Cancer (past 5 years) Men s health issues (%) Loss of sexual desire (in the past 2 years) Premature ejaculation Bladder problems (problems urinating or frequent urination) Prostate problems (for example, enlarged prostate) Pelvic surgery or prostatectomy Peyronie s disease o1 PDE5 inhibitor status (%) Currently using with IIEF-EF Currently using with IIEF-EFo Never used (treatment naive) IIEF-EF (Mean (SD)) 24.0 (5.2) 20.6 (5.2) 22.2 (5.4) 14.9 (4.2) 18.3 (6.7) 17.8 (8.2) 20.0 (6.4) IIEF-EF severity groups Severe Moderate Mild/moderate Score (17 21) Mild (Score 22 25) No ED (Score X26) a Abbreviations: ED, erectile dysfunction; IIEF-EF, International Index of Erectile Functioning-Erectile Function Domain. Note: Some groups may not total up to 100% because of rounding error. a All men in this category are treated with PDE5 inhibitor. Table 3. Number of codes generated for each domain during concept elicitation and confirmation (Studies 1 5) Domain Study 1 Study 2 Study 3 Study 4 Study 5 Total number of codes applied 1 Understanding ED 6 (33%) 12 (67%) 0 (0%) 0 (0%) 0 (0%) 18 2 Emotional Impact of ED 15 (79%) 2 (11%) 1 (5%) 1 (5%) 0 (0%) 19 3 Social Impact of ED 12 (71%) 3 (18%) 0 (0%) 2 (12%) 0 (0%) 17 4 Impact of ED on Sexual Function 13 (68%) 6 (32%) 0 (0%) 0 (0%) 0 (0%) 19 5 PDE5 inhibitor Impact on Social/Partner 5 (83%) 1 (17%) 0 (0%) 0 (0%) 0 (0%) 6 Relationships 6 PDE5 inhibitor Impact on Erections 13 (76%) 3 (18%) 1 (6%) 0 (0%) 0 (0%) 17 7 PDE5 inhibitor Impact on Sexual Function 14 (70%) 2 (10%) 0 (0%) 1 (5%) 3 (15%) 20 Total 78 (67%) 29 (25%) 2 (2%) 4 (3%) 3 (3%) 116 Abbreviation: ED, erectile dysfunction. & 2013 Macmillan Publishers Limited International Journal of Impotence Research (2013),

5 238 Table 4. Concepts selected for item generation for assessments of confidence and difficulty in performing sexual, the resulting items and supporting quotes Concepts CPSIQ items DPSIQ items Supporting quote Currently, how would you rate your confidence to do the following: a Thinking about only the last time you and your partner attempted sexual, how difficult was it for you toy b 1 Ability to get an Get an hard enough for you to have sexual Get an hard enough for you to have sexual Q: How would you describe erectile dysfunctiony A: Just can t get it upyyour apparatuses just don t work (Study 2, age 59 years, African American) Q: So tell me about the erectile dysfunctiony A: A lot of times I couldn t either get an or maintain an. (Study 1, age 32 years, Asian) 2 Hardness (firmness) of hard have sexual hard have sexual Q: What s the most impactful symptom (of ED)? A: For me, it s, I call it the half hard. It s, that half hard, it s just, man. Falling out or slipping out, just not there. (Study 1, age 44 years, Caucasian) Q: What psychological benefits (from PDE5 inhibitors)? A: Well, you re not going to be concerned about not having a nice, hard. It s going to happen. (Study 2, age 50 years, Caucasian) 3 Ability to ejaculate or have an orgasm have an orgasm or ejaculate have an orgasm or ejaculate Q: So without the drug, would be over very quickly? A: Yes, quickly. Q: Because you d try to make it happen before you lost your. A: Right. I would actually work harder and harder and it seemed like the physical exertion actually would drain the as much as help it. Q: Because you d be working harder to try to ejaculate. A: Right, right, to try and maintain, exactly, try to maintain the stimulation, exactly. And then I d be worn out and then I d have to sit back, and then after I sit back the would dissipate. (Study 1, age 44 years, Caucasian) Q: How is sex different when you re taking these pills? A: Because, you know, you ve got to understand before I started taking them, it was just like I couldn t penetrate and boom, I had, it was like penetrate and 30 seconds, it was over. Q: So now you re taking longer to ejaculate. A: It allows me, I mean, it allows me to get some satisfaction. Mostly it allows me to get some satisfaction. (Study 2, age 60 years, African-American) 4 Ability to sexually satisfy partner sexually satisfy sexually satisfy c Q: Without the (PDE5 inhibitor), you can get the? A: Right, but it doesn t stay. (Study 2, age 47 years, Latino) A: It s like in archery. It s not really you against an opponent, it s you against that target. You re worried if the would satisfy your woman and then you get that fear that you re not going to be able to really perform the way she wants you to and then it just dies off. (Study 2, age 49 years, Caucasian) Q: How do you feel when this (not getting hard enough to penetrate) happens? A: You don t feel that you re satisfying, obviously. So it s not a great feeling. (Study 4, age 43 years, Caucasian) Q: What would you think benefits (of PDE5 inhibitors) would be? A: Well, she s having satisfying sex instead of being-she s able to achieve orgasm if I can stay erect for a longer time, which before was a problem. (Study 4, age 35 years, Latino) 5 Length of time can be maintained during sexual enough for sexual to last in duration as long as you and would like it to last enough for sexual to last in duration as long as you and would like it to last c Q: So how long does sex last when you re taking (PDE5 inhibitor) and how long does sex last when you re not taking (PDE5 inhibitor)? A:When I m not taking it definitely under five minutes, but sometimes less than one minute. And when I m taking it it s a different story. I mean, it could happen for an hour. (Study 1, age 38 years, Caucasian) Q: So you don t have to worry about losing your. A: Yeah, probably with an early and probably even having climaxing. Q: Without the pills. A: No, with the pills you go longer and can have sex longer. Q: So it kind of delays climax? A: It seems to for me just because you are stiffery(study 2, age 60 years, Caucasian) International Journal of Impotence Research (2013), & 2013 Macmillan Publishers Limited

6 Table 4. (Continued ) 239 Concepts CPSIQ items DPSIQ items Supporting quote Currently, how would you rate your confidence to do the following: a Thinking about only the last time you and your partner attempted sexual, how difficult was it for you toy b 6 Ability to have variety in sexual, such as changing positions 7 Ability to control when to ejaculate 8 Ability to control when getting an 9 Spontaneity of sexual (timing is not a problem) 10 Ability to have sexual as often as you and want to enough to try different sexual positions if you or would like to Have control over when you ejaculate or have an orgasm Have control over when you have an Be spontaneous (not have to plan the time when you and your partner will have sexual ) Have sexual as often as you and want to, given other life demands Q: What kind of impact has ED had on your life? A: But now I mean it seems that now she can and prior (to taking PDE5 inhibitors) she could never get on top, because if I laid on my back, then my would disappear immediately, almost, especially when I m inside her, then that s a real I can just see and feel the disappointment in her... (Study 1, age 44 years, Caucasian) Q: Does that mean that before (using PDE5 inhibitors) you would ejaculate more quickly, or you would just lose the? A: Well you couldn t change positions. I always found I had to keep, at the peak of excitement to keep the, and therefore I couldn t, I just couldn t change different things because I d say oh I m going to lose the excitement and lose the. Now I don t worry about that. Just as the guys were saying, change to a different position it s not going to go away. (Study 1, age 61 years, Caucasian) Q: You ejaculated. So there was no way to stop it. A: I felt that I had to get it done before, and this feels like the way it used to feel where I can just sit or talkyi have control over that. (Study 2, age 61 years, Latino) Q: So what do you think bothers you (about ED) the most? A: yjust the unpredictable, because when you want to make love to a woman, you just want to, you don t want to worry about this... (Study 2, age 48 years, mixed ethnicity) Q: Whereas with (PDE5 inhibitor), it s... LA: You don t have any time schedule. You don t have anything where you have to do anything, or not do anythingyyou re going to be able to have an, but you don t have to have one. You can have sex, but you don t have to have sex, and you can do it for as long as it s just a normal amount. It isn t that you re totally in control because you re never totally in control with sex, but it s like it used to be. (Study 2, age 61 years, Latino) Q: How is sexual different now than it used to be before ED? A: It seems like a job now, like a chore, whereas before it was joy, it was just spontaneous, it was natural. (Study 5, age 66 years, Latino) Q: yany other aspect of erectile dysfunctionyaffected you..? A: Yeah, it s become a timing issue. It s like, you know, in my mind, I have to plan sex, plan when to have sex with it, you know, to maximize my efforts, because I am, you know, on the pill. It s not quite as spontaneous as it was in my younger, you know, younger years. (Study 3, age 61 years, African- American) Q: What about an intensified intimacy (with PDE5 inhibitors)? A: Sequentially there may be some, you know, an hour or two between them. If you re on vacation you go out to dance, whatever, you come back in and you re going at it again. (Study 1, age 70 years, Caucasian) Q: So, how do you make the decision of when you re going to take (your PDE5 inhibitor)? A: My wife and I start playful texts during the course of the day. Q: So, she doesn t say, take the pill, but like what would she text you? A: y I want you, something like that. So, I know later on that night when I get home, we re about to have sexual. Q: So, you re not really talking about it once you get home, even though you re both there, but she s texting you to sort of like say, this is going to happen tonight. A: Yes. (Study 1, age 23 years, African-American) Abbreviations: CPSIQ, Confidence in Performing Sexual Intercourse Questionnaire; DPSIQ, Difficulty in Performing Sexual Intercourse Questionnaire; ED, erectile dysfunction. a Response set is a 7-point Likert-type scale with (1) Extremely low to (7) Extremely high. b Response set ia a 5-point Likert-type scale with (1) Unable to do last time to (5) Not difficult at all to do last time. c Item eliminated based on cognitive interviews. & 2013 Macmillan Publishers Limited International Journal of Impotence Research (2013),

7 240 that the concepts on which items are based are relevant (experienced by many) and important (priority for treatment effect) to the target population. The concept elicitation studies led to the identification of seven domains pertaining to men s experience of ED and its treatment. Although all of these domains clearly capture the impact of ED, four domains (Understanding ED, Emotional Impact of ED, Social Impact of ED and PDE5 inhibitor Impact on Social Partner Relationships) were excluded from consideration for item generation. Although the psychosocial impact of ED as represented by these four domains is important and supported by other qualitative studies, the concepts included in the domains were not amenable to an assessment of confidence in performing sexual or difficulty in performing sexual. It should be noted that the CPSIQ was intended to measure the impact of ED on men s confidence in their ability to perform a certain activity or behavior (that is, self-efficacy) rather than its impact on loss of confidence, self-esteem, a concept code that emerged within the Emotional Impact of the ED domain. From the remaining three domains, Impact of ED on Sexual Function, Impact of PDE5 inhibitors on Erections and Impact of PDE5 inhibitors on Sexual Function, 10 concepts were identified to form the framework of the CPSIQ and, originally, 5 of those 10 concepts for the DPSIQ. These concepts were consistently and frequently mentioned by study participants regardless of participants ED severity, treatment status or comorbidities, thereby demonstrating their importance and relevance. The identification of these concepts also confirmed that while getting and maintaining an hard enough for sexual are key to a perception of treatment benefit, the extent to which men feel they are able (that is, confident that they can perform) to have an orgasm, have control over their and ejaculation, have reasonable frequency, timing and duration of sexual and believe their partner is sexually satisfied are also important considerations in their perception of ED treatment benefit. In the case of rapidly acting treatment such as PDE5 inhibitors, Patrick et al. 17 argue that short, timely and frequent assessments are preferred over those that may ask respondents to average treatment effect over longer periods of time (for example, 4 weeks). The IIEF-EF confidence item has a recall period of 4 weeks, whereas the CPSIQ has a recall period of currently. Cognitive interviewing indicated that men may think about the recent past (for example, last week) to detemine their current status but understood and agreed that the CPSIQ recall period is appropriate. Therefore, data gathered from the CPSIQ may complement and confirm data gathered from existing ED instruments with longer recall periods. The DPSIQ is somewhat similar in content to another event-based PRO instrument that has been used in clinical trials of ED treatment, the Sexual Encounter Profile However, the yes/no response set of the Sexual Encounter Profile limits score interpretation to a quantified measure of success over time, whereas the polychotomous response set (for example, Likert-type response scale) of the DPSIQ potentially provides a meaningful evaluation of men s difficulty in sexual functioning. Limitations A limitation of the study was that for all the six studies, ED was not clinically verified. The diagnosis of ED was based on participants IIEF-EF score. PDE5 inhibitor treatment status was verified by a participant bringing in a prescription or medication bottle to the interview or focus group rather than physician verification. Finally, as with all qualitative research, the results are used primarily for generating hypotheses or new information, in this case, questionnaire items, and not hypothesis testing. For men with ED, confidence and difficulty in performing sexual go beyond simply getting and maintaining an and completing. The extent to which they experience specific elements of normal sexual drives their perception of treatment benefit. The CPSIQ and DPSIQ have been developed according to the regulatory guidelines, but the importance of the CPSIQ and DPSIQ as complementary measures to existing instruments will need to be confirmed in quantitative analyses that test their reliability, validity and responsiveness to ED treatment. CONFLICT OF INTEREST RH and AS are full-time employees and stockholders of Eli Lilly and Company. JH is President and CEO of The Henne Group, which has completed research agreements with Eli Lilly and Company. MM is a former employee of Eli Lilly and Company. ACKNOWLEDGEMENTS We thank Dr Stanley E. Althof, Dr Raymond C. Rosen, and Dr Allen Seftel for valuable input into the development of the Confidence and Difficulty in Performing Sexual Intercourse Questionnaires. This study was funded by Eli Lilly and Company. REFERENCES 1 Althof SE, O Leary MP, Cappelleri JC, Crowley AR, Tseng LJ, Collins S. Impact of erectile dysfunction on confidence, self-esteem and relationship satisfaction after 9 months of sildenafil citrate treatment. J Urol 2006; 176: Althof SE. Quality of life and erectile dysfunction. Urology 2002; 59: Araujo AB, Durante R, Feldman HA, Goldstein I, McKinlay JB. The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from the Massachusetts Male Aging Study. 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