Development and validation of a novel patient-reported outcome measure in people with episodic migraine and chronic migraine: The Activity Impairment in Migraine Diary.

OBJECTIVE: To evaluate the content validity and psychometric properties of the Activity Impairment in Migraine Diary (AIM-D). BACKGROUND: Measuring treatment effects on migraine impairment requires a psychometrically sound patient-reported outcome (PRO) measure developed consistent with U.S. Food and Drug Administration guidance. METHODS: The AIM-D was created from concepts that emerged during qualitative interviews with five clinicians experienced in treating migraine and concept elicitation (CE) interviews with 40 adults with episodic migraine (EM) or chronic migraine (CM). The initial version was refined based on three waves of cognitive interviews with 38 adults with EM or CM and input from a panel of clinical and measurement experts. The AIM-D was psychometrically evaluated using data from 316 adults with EM or CM who participated in a 13-week prospective observational study. Study participants completed PRO assessments including the AIM-D and a daily headache diary. Exploratory and confirmatory factor analysis were used to determine the factor structure. The reliability, validity, and responsiveness of the AIM-D were assessed. Additional PRO measures including the Patient Global Impression - Severity (PGI-S), Migraine Specific Quality of Life Questionnaire, Version 2.1 Role Function-Restrictive domain, and Headache Impact Test were used for psychometric evaluation of the AIM-D. RESULTS: Based on CE interviews with adults with migraine and input from an expert panel, activity impairment was identified as the target in the preliminary conceptual framework, which had two domains: performance of daily activities (PDAs) and physical impairment (PI). Revision of the draft AIM-D through multiple rounds of cognitive interviews and expert panel meetings resulted in a content valid 11-item version. Exploratory factor analysis supported both one- and two-domain structures for the AIM-D, which were further supported by confirmatory factor analysis (factor loadings all >0.90). The AIM-D domains (PDA and PI) and total score showed high internal consistency reliability (Cronbach's alpha 0.95-0.97), acceptable test-retest reliability for weekly average scores (intraclass correlation coefficient >0.60 for participants with no change in PGI-S between baseline and week 2), and good convergent and known-groups validity. There was evidence of responsiveness based on changes in PGI-S score and monthly migraine days. CONCLUSION: The AIM-D is a content valid and psychometrically sound measure designed to evaluate activity impairment and is suitable for use in clinical trials of preventive treatments for EM or CM.

Functionality, satisfaction, and global impression of change with ubrogepant for the acute treatment of migraine in triptan insufficient responders: a post hoc analysis of the ACHIEVE I and ACHIEVE II randomized trials.

BACKGROUND: Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. METHODS: This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. RESULTS: In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. CONCLUSIONS: In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016.

Can Methods Developed for Interpreting Group-level Patient-reported Outcome Data be Applied to Individual Patient Management?

BACKGROUND: Patient-reported outcome (PRO) data may be used at 2 levels: to evaluate impacts of disease and treatment aggregated across individuals (group-level) and to screen/monitor individual patients to inform their management (individual-level). For PRO data to be useful at either level, we need to understand their clinical relevance. PURPOSE: To provide clarity on whether and how methods historically developed to interpret group-based PRO research results might be applied in clinical settings to enable PRO data from individual patients to inform their clinical management and decision-making. METHODS: We first differentiate PRO-based decision-making required at group versus individual levels. We then summarize established group-based approaches to interpretation (anchor-based and distribution based), and more recent methods that draw on item calibrations and qualitative research methods. We then assess the applicability of these methods to individual patient data and individual-level decision-making. FINDINGS: Group-based methods provide a range of thresholds that are useful in clinical care: some provide screening thresholds for patients who need additional clinical assessment and/or intervention, some provide thresholds for classifying an individual's level of severity of symptoms or problems with function, and others provide thresholds for meaningful change when monitoring symptoms and functioning over time during or after interventions. Availability of established cut-points for screening and symptom severity, and normative/reference values, may play into choice of PRO measures for use in clinical care. Translatability of thresholds for meaningful change is more problematic because of the greater reliability needed at the individual-level versus group-level, but group-based methods may provide lower bound estimates. Caution is needed to set thresholds above bounds of measurement error to avoid "false-positive changes" triggering unwarranted alerts and action in clinic. CONCLUSIONS: While there are some challenges in applying available methods for interpreting group-based PRO results to individual patient data and clinical care-including myriad contextual factors that may influence an individual patient's management and decision-making-they provide a useful starting point, and should be used pragmatically.

Content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form with advanced breast cancer patients.

BACKGROUND: The purpose of this study is to evaluate the content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. METHODS: Cognitive debriefing interviews sought to evaluate patients' ability to read, understand, and meaningfully respond to the questionnaires, as well as to evaluate the questionnaires' relevance in the target patient population. Interviews were conducted by telephone and lasted approximately 90 min. Audio recordings were transcribed, anonymized, and analyzed using qualitative data analysis software. RESULTS: Fifteen cognitive debriefing interviews were conducted with women (mean age 66.0 years [standard deviation = 12.4]). Patients reported metastases in the bone (86.7%), liver (20.0%), lung (13.3%), skin (6.7%), and lymph node (6.7%) (not mutually exclusive). All patients for whom data were available demonstrated understanding of the instructions and the recall period of the NFBSI-16 (n = 14/14, 100.0%) and the PROMIS (n = 14/14, 100.0%). Greater than 90% of patients demonstrated understanding of each of the items in the NFBSI-16 and the PROMIS. Greater than 70% of patients demonstrated understanding of the response options of the NFBSI-16, > 90% understood response options of PROMIS Items 1-6, and ≥ 50% understood response options of PROMIS Items 7-10. Conceptual relevance was supported for most items in both questionnaires based on patients' reports of experiencing the concepts as part of their breast cancer experience. CONCLUSIONS: The results of the cognitive debriefing interviews provide evidence that the NFBSI-16 and PROMIS Physical Function Short Form 10b have content validity in the HR+/HER2- advanced breast cancer patient population. Patients may benefit from additional instructions at the point the response options reverse direction in the PROMIS.

Clostridium difficile Infection-Daily Symptoms (CDI-DaySyms™) questionnaire: psychometric characteristics and responder thresholds.

BACKGROUND: The purpose of the current study was to determine the final content validation, psychometric characteristics, clinically meaningful improvement, and responder thresholds of the Clostridium difficile infection (CDI)-Daily Symptoms (CDI-DaySyms™) patient-reported outcome (PRO) questionnaire. METHODS: This validation study was part of two phase III studies (NCT01987895 and NCT01983683) conducted in patients with mild-to-moderate or severe CDI who completed the CDI-DaySyms™ daily throughout the treatment period. The questionnaire was evaluated in three stages: final PRO item content validation (Stage I); psychometric evaluation of reliability and construct validity (Stage II); and determination of clinically meaningful improvement and responder thresholds using distribution-based methods (Stage III). RESULTS: The analysis included 168 patients. Most patients were female and Caucasian with mild-to-moderate CDI. The mean age was 57.1 years. Initial item analysis supported by confirmatory factor analysis demonstrated the relevance of 10 items grouped into three distinct domains (Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms). Domain scores demonstrated acceptable internal consistency and test-retest reliability, were sensitive to change, and correlated in expected directions with other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of - 1.00, - 0.80, and - 0.70 in the Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms domains, respectively. CONCLUSIONS: The CDI-DaySyms™ is a valid measure of patient-reported CDI symptoms, with good measurement properties, which supports its utility as an endpoint in clinical studies. Further studies confirming responder thresholds based on anchor-based methods are required. TRIAL REGISTRATION: NCT01987895 , registered November 20, 2013; NCT01983683 , registered November 14, 2013.

U.K. utility weights for the EORTC QLU-C10D.

The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely used cancer-specific quality of life questionnaire, EORTC QLQ-C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU-C10D. A U.K. online panel was quota-sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice-pairs, each comprising two QLU-C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU-C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is -0.083, which is considered slightly worse than being dead. The U.K.-specific utility weights will enable cost-utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD. METHODS: A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments. RESULTS: The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach's α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified. CONCLUSIONS: The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

Evaluation of options for presenting health-states from PROMIS® item banks for valuation exercises.

PURPOSE: Health status descriptive systems based on item response theory (IRT), such as the Patient-Reported Outcomes Measurement Information System (PROMIS®), have item banks to measure domains of health. We developed a method to present such banks for health-state valuation. METHODS: We evaluated four different presentation approaches: a single item (1S), 2 items presented separately (2S), 2 items presented together (2T), or 5 items presented together (5T). We evaluated these four approaches in three PROMIS item banks (depression, physical function, and sleep disturbance). Adult community members valued health-state descriptions using the visual analog scale and standard gamble methods. We compared the approaches by the range of item bank theta scores captured, participants' assessments of difficulty (1 = very easy to 7 = very hard), and exit interviews. RESULTS: Participants (n = 118) ranged in age from 18 to 71; 63% were female and 54% were white. The 1S approach captured the smallest range of theta scores. A monotonic relationship between theta score and mean standard gamble estimate was found with all approaches except 2S. Across all 3 item banks, mean difficulty assessments were 2.35 (1S), 2.69 (2T), 2.78 (5T), and 2.80 (2S). In exit interviews, participants generally found all four approaches similarly meaningful and realistic. CONCLUSIONS: Creating health descriptions by presenting 2 items maximized the range of theta while minimizing difficulty and maintaining a monotonic relationship with utility estimates. We recommend this approach for valuation of IRT-based descriptive systems such as PROMIS.

Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.

Importance: Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. Objective: To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). Design, Setting, and Participants: The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. Results: The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. Conclusions and Relevance: The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

BACKGROUND: The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. AIM: To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. METHODS: A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. MAIN OUTCOME MEASURES: Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. RESULTS: One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. CLINICAL IMPLICATIONS: The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. STRENGTHS AND LIMITATIONS: Careful consideration was given to the selection of the final HIS-Q-SF items based on quantitative data and clinical expert feedback. Overall, the reduced set of items demonstrated strong psychometric properties. Testosterone levels for the participating men were not as low as anticipated, which could have limited the ability to examine the relations between the HIS-Q-SF and testosterone levels. Further, the analyses used data collected through administration of the full HIS-Q, and future studies should administer the standalone HIS-Q-SF to replicate the psychometric analyses reported in the present study. CONCLUSION: Similar to the original HIS-Q, the HIS-Q-SF has evidence supporting reliability, validity, and responsiveness. The short form includes a smaller set of items that might be more suitable for use in clinical practice or academic research settings. Gelhorn HL, Roberts LJ, Khandelwal N, et al. Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF). J Sex Med 2017;14:1046-1058.

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

The focus of this article, the fourth in the series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, is on aspects of clinical trial design and measurement that are specific to clinical trials for treatments of female sexual dysfunction. Challenges in this area include the limited extent of treatment development and clinical trial research across the spectrum of female sexual dysfunctions, changing regulatory considerations, changing diagnostic criteria for female sexual dysfunction, and the need to articulate assessment procedures to these changes. Discussion focuses on approaches to addressing these challenges in clinical trials in female sexual dysfunction.

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.

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

OBJECTIVES: The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. METHODS: This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. RESULTS: Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. CONCLUSION: The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary.

OBJECTIVE: The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient-reported outcome (PRO) measure for assessing the impact of migraine on physical functioning. METHODS: In a prospective, observational study, adults with episodic migraine (EM) or chronic migraine (CM) used an eDiary to complete the MPFID (assessing daily impacts of migraine on physical function) and a headache diary (capturing migraine days, migraine pain intensity, and migraine interference) each day, and other PRO instruments related to migraine. Item-level evaluation, item response theory (IRT), and exploratory factor analysis (EFA) methods were applied to identify domains, select final MPFID items, and develop scoring procedures. Psychometric properties of the final 13-item MPFID were evaluated using confirmatory factor analysis and tests of reliability (Cronbach's α for internal consistency and intra-class correlation [ICC] for test-retest) and validity (convergent and known-groups). RESULTS: The study enrolled 569 adults with chronic or episodic migraine, mean (SD) age 39.9 (12.0) years and 87.2% female. Item-level analyses based on interim data informed selection of a set of 13 items for the MPFID, through evaluation of floor/ceiling effects, item-to-item correlations, factor loadings, and IRT-based fit/misfit statistics. Two domain scores (EA: Impact on Everyday Activities; PI: Physical Impairment) and a global item score for impact on everyday activities were identified. EA and PI domains exhibited high internal consistency (α = 0.97; α = 0.93) and good test-retest reliability among stable subjects (ICCs = 0.74 and 0.77). Convergent validity was demonstrated by moderate correlations (r = ±0.50-0.68; P < .0001) between MPFID domain scores and number of migraine days, headache days, bed days, and other migraine-related PRO instruments. EA and PI scores differentiated between groups who varied by number of migraine days, migraine interference levels, migraine pain intensity, and median split groups of scores based on other PROs instruments (P < .05). CONCLUSIONS: The MPFID has robust psychometric properties (ie, reliability and validity). Findings supported two distinct domains about the impact of migraine on physical functioning: Impact on Everyday Activities and Physical Impairment. Both domain scores showed evidence of excellent reliability and construct validity in assessing the impacts of migraine on physical functioning.

Selection of key health domains from PROMIS® for a generic preference-based scoring system.

PURPOSE: We sought to select a parsimonious subset of domains from the patient-reported outcomes measurement information system (PROMIS®) that could be used for preference-based valuation. Domain selection criteria included face validity, comprehensiveness, and structural independence. METHODS: First, 9 health outcomes measurement experts selected domains appropriate for a general health measure using a modified Delphi procedure. Second, 50 adult community members assessed structural independence of domain pairs. For each pair, the participant was asked if it were possible to have simultaneously good functioning in domain 1 but poor functioning in domain 2, and vice versa. The community members also rated the relative importance of the domains. Finally, the experts selected domains, guided by community members' judgments of structural independence and importance. RESULTS: After 3 rounds of surveys, the experts agreed on 10 potential domains. The percent of pairs deemed structurally independent by community members ranged from 50 to 95 (mean = 78). Physical Function, Pain Interference, and Depression were retained because of their inclusion in existing preference-based measures and their importance to community members. Four other domains were added because they were important to community members and judged to be independent by at least 67% of respondents: Cognitive Function-Abilities; Fatigue; Ability to Participate in Social Roles and Activities; and Sleep Disturbance. CONCLUSION: With input from measurement experts and community members, we selected 7 PROMIS domains that can be used to create a preference-based score.

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.

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 patient's health status that come directly from the patient (ie, without the interpretation of the patient's 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 patient's symptoms, functioning, and well-being. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient's perspective.

Development of the Hypogonadism Impact of Symptoms Questionnaire Short Form: Qualitative Research.

INTRODUCTION: Hypogonadism in men is often associated with poor libido, erectile dysfunction, irritability, fatigue, and psychological and relationship problems. Many of these symptoms can be best assessed through patient report. The 28-item Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) was developed to evaluate hypogonadism symptoms in men with low testosterone in the context of clinical trials. AIM: To develop a briefer version of the HIS-Q that could be practical for use in treatment settings. METHODS: Participants with low testosterone levels and symptoms consistent with hypogonadism were recruited through clinical sites. Focus groups and interviews were conducted to elicit symptom concepts and identify those that were most relevant to patients, including changes as a consequence of treatment. MAIN OUTCOME MEASURES: Systematic analysis of the qualitative data and expert clinician input were used to develop the HIS-Q short form (HIS-Q-SF). One-on-one cognitive interviews were conducted to confirm the content validity of the HIS-Q-SF. RESULTS: Thirty-five men participated in this qualitative research. Concept elicitation was conducted through focus group discussions (n = 18) and telephone interviews (n = 2); then, the draft HIS-Q-SF was evaluated through cognitive interviews (n = 15). The mean age of total sample was 53.2 ± 6.8 years, and the mean serum total testosterone level was 184.9 ± 55.2 ng/dL. Results suggest that the HIS-Q-SF has demonstrated content validity, including the content coverage, comprehensibility, and the appropriateness of the response options and recall period. The final version of the HIS-Q-SF includes 17 items and is aligned with the original longer version of the instrument. CONCLUSION: The HIS-Q-SF is a comprehensive measurement of hypogonadism symptom severity in men. Content coverage and content validity were confirmed. The instrument will be evaluated further to establish the psychometric characteristics and to assess the utility of the measurement in clinical treatment settings.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire.

INTRODUCTION: The Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) is a patient-reported outcome measurement designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment. AIM: To conduct item analysis and reduction, evaluate the psychometric properties of the HIS-Q, and provide guidance on interpreting the instrument score. METHODS: A 12-week observational, longitudinal study of hypogonadal men was conducted. Participants completed the HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants also completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12 Health Survey, and the Patient-Reported Outcomes Measurement Information System Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (at baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change measurements and a clinical form. MAIN OUTCOME MEASURES: Individual item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. RESULTS: In total, 177 men participated in the study (mean age = 54.1 years, range = 23-83). The original 53-item draft HIS-Q was reduced to 28 items; the final instrument included five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For all domains, test-retest reliability was acceptable (intraclass correlation coefficients > 0.70), construct validity was good (|r > 0.30| for all comparisons). Known-groups validity was demonstrated for all HIS-Q domain scores, subdomain scores, and the total score as measured by the Clinical Global Impression of Severity, and total testosterone level at baseline (P < .05 for all comparisons). All domains and subdomains were responsive to change based on patient-rated anchor questions (P < .05 for all comparisons). CONCLUSION: The final 28-item HIS-Q is reliable, valid, and responsive. The HIS-Q is suitable for inclusion in future clinical trials to help characterize the effects of testosterone replacement therapy.

A PROMIS Measure of Neuropathic Pain Quality.

OBJECTIVES: Neuropathic pain (NP) is a consequence of many chronic conditions. This study aimed to develop an unidimensional NP scale with scores that represent levels of NP and distinguish between individuals with NP and non-NP conditions. METHODS: A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without NP conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a holdout sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. NP scale scores were evaluated in terms of the reliability, validity, and ability to distinguish between participants with and without conditions typically associated with NP. RESULTS: Of the 42 initial items, 5 were identified for the Patient-Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality Scale. T scores exhibited good discriminatory ability on the basis of receiver-operator characteristic analysis. Score thresholds that optimize sensitivity and specificity were identified. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. CONCLUSIONS: The five-item Patient-Reported Outcome Measurement Information System (PROMIS PQ-Neuro) Neuropathic Pain Quality Scale is a short and practical measure that can be used to identify patients more likely to have NP and to distinguish levels of NP. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain).