Introduction: Although alopecia areata (AA) profoundly impacts patients' physical appearance, emotional state, and daily activities, no treatment approved for AA currently exists. Patient-reported outcome (PRO) instruments currently used to capture patients' AA experiences do not meet the requirements to support claims of treatment benefit as described in the US Food and Drug Administration's 2009 PRO guidance. Our objective was to explore the consequences and priority treatment outcomes among individuals with AA and develop a PRO measure consistent with regulatory requirements that assesses these priorities and represents clinical benefit from the AA patient perspective. Methods: Targeted literature and instrument reviews informed an initial concept set. Concept elicitation interviews with 20 adults with AA confirmed the relevance and importance of the initial concepts, identified additional relevant concepts, and informed an AA consequence model. Thematic analysis yielded a draft item pool, which was evaluated through two iterative rounds of cognitive debriefing interviews with 16 patients with AA (9 adults; 7 adolescents). Results: Hair loss was the primary consequence of importance to patients with AA. Patients emphasized the need to differentiate hair loss by location: scalp, eyebrows, eyelashes, and body. Consequences of AA include difficulty conducting daily activities, particularly outdoor activities and exercise, and emotional impacts such as sadness, frustration, and negative selfimage. Following cognitive debriefing interviews, 11 items were included to form the Alopecia Areata Patient Priority Outcome (AAPPO), assessing AA-related symptoms and impacts over the past week. Conclusions: The AAPPO is a novel, contentvalid PRO that captures the consequences of AA of the highest priority to patients.

Introduction: Individuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA. Methods: Scoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged C 18 years, 36 adolescents aged 12-17 years) with Severity of Alopecia Tool (SALT) C 25% scalp hair loss. Results: Exploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (a C 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients C 0.78). All HL item scores demonstrated strong construct validity (r C 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r C 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25-49% SALT subgroup versus those with highest SALT scores (76-100%); however, ES mean domain scores were better in the SALT 76-100% subgroup in the same comparison (p \ 0.0001). Using AASIS and MCS score-created subgroups, ES and AL mean domain scores demonstrated hypothesized differences across subgroups (all p values \ 0.0001). Conclusion:The AAPPO questionnaire is a reliable, valid disease-specific measure of hair loss severity and impact in individuals with AA.

BackgroundMetastatic castration-resistant prostate cancer (mCRPC) and its treatment significantly affect health-related quality of life (HRQOL). Our objectives were to evaluate and compare patient-reported outcome (PRO) claims granted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 5 recently approved mCRPC treatments and to examine key characteristics, development, and measurement properties of the PRO measures supporting these claims against current regulatory standards.MethodsFive products approved for treatment of mCRPC by the FDA and the EMA (2010–2013) were examined: enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and radium Ra 223 dichloride. United States (US) drug approval packages and European Public Assessment Reports were reviewed. PRO claims in the US labels and European Summaries of Product Characteristics and supporting measures were identified. For PRO measures supporting claims, a targeted literature review was conducted to identify information on key characteristics and measurement properties; this information was compared against FDA PRO guidance criteria.ResultsNine PRO “claims” were granted across 4 of 5 products reviewed. The EMA granted more claims (7 claims—4 for pain, 3 for HRQOL) than the FDA (2 claims, both for pain). The Brief Pain Inventory–Short Form (BPI-SF) worst pain item supported most pain claims and was the only measure supporting US claims. EMA pain claims were supported by BPI-SF worst pain (n = 2) and average pain (n = 1) items and the McGill Pain Questionnaire Present Pain Intensity component (n = 1). EMA HRQOL claims were supported by the Functional Assessment of Cancer Therapy–Prostate Module (n = 2) and the EuroQol 5 Dimensions with visual analogue scale (n = 1). Pain and prostate cancer–specific HRQOL measures supporting claims met US regulatory standards for construct validity, reliability, and responsiveness; these properties were strongest for the BPI-SF worst pain item. Only the BPI-SF worst pain item has documented content validity in mCRPC.ConclusionsPRO label claims were commonly granted across the mCRPC products reviewed. Among the measures reviewed, only the BPI-SF worst pain item supported US label claims. The BPI-SF worst pain item is recommended for pain assessment for the evaluation of new mCRPC treatments.

PurposeTo conduct an initial psychometric evaluation of the reliability and validity of the Hypoparathyroidism Symptom Diary (HPT-SD).Patients and methodsData were collected during a cross-sectional, observational study. Participants with self-reported hypoparathyroidism (HPT) completed the HPT-SD, the Functional Assessment in Cancer Therapy–Cognitive Function (FACT-Cog), the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), and the Hospital Anxiety and Depression Scale (HADS) measures. Item- and scale-level internal consistency reliability, known-groups validity, and construct validity were evaluated. Subscales were identified and preliminary scoring algorithms were developed.ResultsThe study included 52 participants (mean age, 51 years). Overall, the measurement properties of the HPT-SD were very good. Item-level response frequency distributions showed evidence of possible floor effects for four muscle-related symptom items. Inter-item correlations revealed a pattern of relationships among symptom items (r=0.3–0.8) and among impact items (r=0.5–0.7) and provided evidence for two HPT-SD subscales: Symptoms and Impacts. Construct validity correlations supported a priori convergent validity hypotheses (|r|≥0.4) between HPT-SD subscales and the FACT-Cog, FACIT-Fatigue, and HADS. Mean HPT-SD Symptom and Impact scores were in the expected direction and significantly different between subgroups of patients with high and low HPT disease severity.ConclusionResults indicate that the HPT-SD is an appropriate measure of HPT-related symptoms and impacts. Floor effects may be attributed to the observational study design: participants manage symptoms with calcium and active vitamin D supplements prior to an escalation in severity. Future studies should assess the HPT-SD measurement properties using longitudinal study designs.

IntroductionA patient-reported outcome (PRO) measure specific to chronic hypoparathyroidism is lacking to facilitate the evaluation of treatment. A PRO measure that followed the recommendations of the US Food and Drug Administration (FDA) PRO guidance was created to address key hypoparathyroidism symptoms.MethodsA literature review was conducted to identify symptoms of hypoparathyroidism and any existing PRO measures appropriate for evaluating these symptoms, followed by concept elicitation interviews involving six individuals with hypoparathyroidism. On the basis of the results of the literature review and interviews, a draft item pool was developed and refined through two sets of cognitive debriefing interviews with six additional patients. A translatability assessment was also conducted to evaluate concepts, phrases, or components of the items that could be problematic in future translations and to identify culturally specific phrasing.ResultsNo PRO measures appropriate to address hypoparathyroidism symptoms documented in the literature were identified. Qualitative research participants included 11 women and one man, with an average age of 49 years; the majority (10) of these participants were white. Concept elicitation interview results were generally consistent with the results of the literature review; the most commonly reported symptoms included issues with cognition, often described as “brain fog” (n = 6), muscle cramping (n = 5), tingling (n = 5), and muscle spasms or twitching (n = 4). The initial draft item pool included 20 items; based upon participant feedback, the final Hypoparathyroidism Symptom Diary comprised 13 items and was found to be easily understood and relevant to the participants. No significant issues were identified by the translatability assessment.ConclusionThe Hypoparathyroidism Symptom Diary was developed following the recommendations of the FDA’s PRO guidance. The measure addresses a comprehensive set of symptoms, as well as key impacts of hypoparathyroidism deemed important by patients.FundingShire Human Genetic Therapies, Inc., Lexington, MA, USA, a member of the Takeda group of companies.