Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. OBJECTIVES: To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. METHODS: Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. RESULTS: Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75-0.94; FACIT-Fatigue range, 0.11-0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test-retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001-0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001-0.0002). CONCLUSIONS: Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP.

Psychometric validation of the generalized pustular psoriasis physician global assessment (GPPGA) and generalized pustular psoriasis area and severity index (GPPASI).

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and life-threatening skin disease often accompanied by systemic inflammation. There are currently no standardized or validated GPP-specific measures for assessing severity. OBJECTIVE: To evaluate the reliability, validity and responder definitions of the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) and Generalized Pustular Psoriasis Area and Severity Index (GPPASI). METHODS: The GPPGA and GPPASI were validated using outcome data from Week 1 of the Effisayil™ 1 study. The psychometric analyses performed included confirmatory factor analysis, item-to-item/item-to-total correlations, internal consistency reliability, test-retest reliability, convergent validity, known-groups validity, responsiveness analysis and responder definition analysis. RESULTS: Using data from this patient cohort (N = 53), confirmatory factor analysis demonstrated unidimensionality of the GPPGA total score (root mean square error of approximation <0.08), and GPPGA item-to-item and item-to-total correlations ranged from 0.58 to 0.90. The GPPGA total score, pustulation subscore and GPPASI total score all demonstrated good test-retest reliability (intraclass correlation coefficient: 0.70, 0.91 and 0.95 respectively), and good evidence of convergent validity. In anchor-based analyses, all three scores were able to detect changes in symptom and disease severity over time; reductions of -1.4, -2.2 and - 12.0 were suggested as clinically meaningful improvement thresholds for the GPPGA total score, GPPGA pustulation subscore and GPPASI total score respectively. Anchor-based analyses also supported the GPPASI 50 as a clinically meaningful threshold for improvement. CONCLUSIONS: Overall, our findings indicate that the GPPGA and GPPASI are valid, reliable and responsive measures for the assessment of GPP disease severity, and support their use in informing clinical endpoints in trials in GPP.

Qualitative study of patients with venous malformations: symptom experiences and content validity of patient-reported outcome measures.

PURPOSE: To determine important symptoms and functional effects of venous malformations (VMs) to assess the content validity of commonly used patient-reported outcome (PRO) measures for use with VM patients. METHODS: This cross-sectional, qualitative study involved cognitive interviews with participants with VM aged ≥ 14 years. From February to June 2016, 11 participants (8 female) with a mean (± standard deviation) age of 31 ± 15 years were recruited from three clinical sites. The following subgroups were evaluated: 5 adults (aged ≥ 18) with trunk/extremity VMs; 3 adolescents (aged 14-17) with trunk/extremity VMs; and 3 adults with head/neck VMs. We evaluated the content validity of the Worst Pain Numeric Rating Scale (NRS), Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Interference 8-item short form, and PROMIS Physical Function 8-item short form. RESULTS: The most common participant-reported VM symptoms were swelling (n = 10), skin discoloration (n = 8), acute episodic pain (n = 8), chronic pain (n = 7), numbness (n = 7), and tingling/burning (n = 6). Participants reported that VMs affected their physical function (n = 10), appearance (n = 10), relationships/social activities (n = 7), and emotional health (n = 3). The Worst Pain NRS and PROMIS Pain Interference measures were relevant to all participants' VM experience. Only adults with head/neck VMs found the PROMIS Physical Function measure to be irrelevant. The assessed PRO measures did not address several symptoms commonly reported by VM patients (swelling, skin discoloration, numbness, and appearance). CONCLUSION: These results suggest that several VM symptoms are not assessed fully by commonly used PRO measures, and that the relevance of functional limitation questions may vary by VM location.

Development and validation of a primary sclerosing cholangitis-specific patient-reported outcomes instrument: The PSC PRO.

Primary sclerosing cholangitis (PSC) is a chronic liver disease associated with inflammation and biliary fibrosis that leads to cholangitis, cirrhosis, and impaired quality of life. Our objective was to develop and validate a PSC-specific patient-reported outcome (PRO) instrument. We developed a 42-item PSC PRO instrument that contains two modules (Symptoms and Impact of Symptoms) and conducted an external validation. Reliability and validity were evaluated using clinical data and a battery of other validated instruments. Test-retest reliability was assessed in a subgroup of patients who repeated the PSC PRO after the first administration. One hundred two PSC subjects (44 ± 13 years; 32% male, 74% employed, 39% with cirrhosis, 14% with a history of decompensated cirrhosis, 38% history of depression, and 68% with inflammatory bowel disease [IBD]) completed PSC PRO and other PRO instruments (Short Form 36 V2 [SF-36], Chronic Liver Disease Questionnaire [CLDQ], Primary Biliary Cholangitis - 40 [PBC-40], and five dimensions [5-D Itch]). PSC PRO demonstrated excellent internal consistency (Cronbach alphas, 0.84-0.94) and discriminant validity (41 of 42 items had the highest correlations with their own domains). There were good correlations between PSC PRO domains and relevant domains of SF-36, CLDQ, and PBC-40 (R = 0.69-0.90; all P < 0.0001), but lower (R = 0.31-0.60; P < 0.001) with 5-D Itch. Construct validity showed that PSC PRO can differentiate patients according to the presence and severity of cirrhosis and history of depression (P < 0.05), but not by IBD (P > 0.05). Test-retest reliability was assessed in 53 subjects who repeated PSC PRO within a median (interquartile range) of 37 (27-47) days. There was excellent reliability for most domains with intraclass correlations (0.71-0.88; all P < 0.001). CONCLUSION: PSC PRO is a self-administered disease-specific instrument developed according to U.S. Food and Drug Administration guidelines. This preliminary validation study suggests good psychometric properties. Further validation of the instrument in a larger and more diverse sample of PSC patients is needed. (Hepatology 2018;68:155-165).

Development of a New Tool for Evaluating the Benefit of Preventive Treatments for Migraine on Functional Outcomes - The Migraine Functional Impact Questionnaire (MFIQ).

OBJECTIVE: The objective of this study was to develop a method for evaluating patient-relevant outcomes of interventions for preventing migraine attacks, followed by an assessment of the content validity of a new patient-reported outcome (PRO) instrument: the Migraine Functional Impact Questionnaire (MFIQ). BACKGROUND: The aim of preventive treatments for migraine is not only to reduce migraine frequency, but also to restore patients' ability to function and improve quality of life. METHODS: A multi-stage process based on best practice methods and regulatory guidelines for ensuring content validity of PRO instruments for evaluating treatment benefit was followed. Qualitative concept elicitation interviews conducted to understand the experiences of adults with migraine underpinned the development of the instrument. The initial stage included the development of a conceptual disease model (CDM) based on information from these interviews. This CDM was used to identify the concepts of interests (COI) to evaluate outcomes of preventive treatments. The results of the interviews were also used in stage 2, to develop a measurement framework for collecting data about these COI. In the third stage, existing instruments were reviewed for coverage of the concepts in the framework and evidence of concept elicitation to the point of saturation, to support content validity. In the fourth stage, an instrument was drafted to evaluate concepts in the framework, based on the qualitative data collected from the interviews. Following a review by clinical and translation experts, the new instrument was tested in adults with migraine in the fifth stage using 2 rounds of cognitive interviews, and was modified based on interview feedback. In the last stage, the instrument was linguistically adapted, using methods recommended for PRO instruments, to ensure conceptual equivalence of language versions for use in international studies. Each language version was tested in at least 5 native speakers using cognitive interviews. RESULTS: Results from the concept elicitation interviews suggested that migraine had an impact on various aspects of functioning. A conceptual framework for evaluating functional outcomes was developed for the concept selected based on a review of the CDM - physical and emotional functioning, every day activities, and social/leisure activities. Existing PROs lacked coverage of some concepts in the conceptual framework, had recall periods that were inappropriate for capturing the experience of COI or did not have evidence of content validity. A novel PRO instrument, the MFIQ, was developed to address these gaps. Cognitive interviews with 9 adults with migraine resulted in minor changes to the items of the MFIQ, and a final round of 8 interviews confirmed the changes were acceptable and supported its validity. The interviews conducted to test linguistic adaptations confirmed conceptual equivalence in the 25 countries evaluated. CONCLUSIONS: Development of the MFIQ followed best measurement practices to ensure content validity and followed regulatory guidelines for PRO instruments to evaluate benefits of treatments. The MFIQ was developed for use in clinical trials or clinical practice settings to track outcomes of preventive treatments that are most relevant to adults with migraine.

Content validity and electronic PRO (ePRO) usability of the Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso) in mesothelioma patients.

PURPOSE: Obtaining qualitative data directly from the patient perspective enhances the content validity of patient-reported outcome (PRO) instruments. The objective of this qualitative study was to evaluate the content validity of the Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso) and its usability on an electronic device. METHODS: A cross-sectional methodological study, using a qualitative approach, was conducted among patients recruited from four clinical sites. The primary target population included patients with pleural mesothelioma; data were also collected from patients with peritoneal mesothelioma on an exploratory basis. Semi-structured interviews were conducted consisting of concept elicitation, cognitive interviewing, and evaluation of electronic patient-reported outcome (ePRO) usability. RESULTS: Participants (n = 21) were interviewed in person (n = 9) or by telephone (n = 12); 71% were male with a mean age of 69 years (SD = 14). The most common signs and symptoms experienced by participants with pleural mesothelioma (n = 18) were shortness of breath, fluid build-up, pain, fatigue, coughing, and appetite loss. The most commonly described symptoms for those with peritoneal mesothelioma (n = 4) were bloating, changes in appetite, fatigue, fluid build-up, shortness of breath, and pain. Participants with pleural mesothelioma commonly described symptoms assessed by the LCSS-Meso in language consistent with the questionnaire and a majority understood and easily completed each of the items. The ePRO version was easy to use, and there was no evidence that the electronic formatting changed the way participants responded to the questions. CONCLUSIONS: Results support the content validity of the LCSS-Meso and the usability of the electronic format for use in assessing symptoms among patients with pleural mesothelioma.

Development and exploration of the content validity of a patient-reported outcome measure to evaluate the impact of migraine- the migraine physical function impact diary (MPFID).

BACKGROUND: Adults with migraine experience substantial reductions in quality of life during and in-between migraine attacks. Clinical and regulatory guidelines encourage the inclusion of patient reported outcomes for the evaluation of benefits of interventions for migraine. METHODS: The conceptual framework and items for a new patient-reported outcome (PRO) instrument, the Migraine Physical Function Impact Diary (MPFID), were developed using scientific methods recommended to ensure content validity of PRO instruments. The MPFID was developed to measure the impact of migraine on physical functioning based on themes raised in concept elicitation (CE) interviews (conducted previously) with adults with migraine. Cognitive interviews were conducted with adults with migraine to further explore content validity. The instrument was modified following an interim analysis of a first round of cognitive interviews, to assess comprehensiveness and clarity of items, instructions, and response options. Refinements were subsequently tested in additional cognitive interviews. RESULTS: The conceptual framework included impacts on physical functioning experienced by most adults with migraine and deemed clinically relevant for measuring the outcome of an intervention for migraine. Concepts in the framework included the impact of migraine on physical impairments (acts) and ability to complete day-to-day activities and perform everyday activities (tasks). MPFID items were generated to evaluate functioning over the past 24 h and to collect data daily, to capture experiences on days with migraine as well as the days in-between migraines. Items asked about needing to rest or lie down; ability to get out of bed, stand up, bend over, walk, perform household chores, do tasks outside the home, keep routines or schedules, get ready for the day, do activities that require concentration or clear thinking; difficulty moving head and body, doing activities requiring physical effort; avoiding interacting with others. Initial modifications based on the first round of cognitive interviews (n = 8) included clarifying instructions, updating three items to enhance specificity and clarity, and revising one item to include gender-neutral language. The second round of interviews (n = 9) confirmed acceptability of revisions and supported content validity. CONCLUSIONS: The results provide qualitative evidence supporting the content validity of the MPFID for evaluating outcomes of interventions for migraine.

Measuring the impact of migraine for evaluating outcomes of preventive treatments for migraine headaches.

BACKGROUND: Migraine is characterized by headache with symptoms such as intense pain, nausea, vomiting, photophobia, and phonophobia that significantly impact individuals' lives. The objective of this study was to develop a strategy to measure outcomes from the patients' perspectives for use in evaluating preventive treatments for migraine. METHODS: This study used a multi-stage process. The first stage included concept identification research through literature review, patient-reported outcome (PRO) instrument content review, and clinician interviews, and resulted in a list of concepts relevant to understand the migraine experience. These results informed the design of the subsequent concept elicitation stage that involved qualitative interviews of adults with migraine to understand their experiences. Information from these two stages was used to develop a conceptual disease model (CDM) of the migraine experience. This CDM was used to identify concepts of interest (COI) to evaluate patient-relevant outcomes for assessing treatment benefit of migraine prophylactics. In the final stage, existing PRO instruments were reviewed to assess coverage of concepts related to the selected COI. RESULTS: Nine articles from 563 screened abstracts underwent full review to identify migraine-relevant concepts. This concept identification and subsequent concept elicitation interviews (N = 32; 21 episodic migraine; 11 chronic migraine) indicated that people with migraine experience difficulties during and between migraine attacks with considerable day-to-day variability in the impact on movement, ability to perform every day and social activities, and emotion. The CDM organized concepts as proximal to and more distal from disease-defining migraine symptoms, and was used to identify impact on physical function as the key COI. The item level review of PRO instruments revealed that none of the existing PRO instruments were suitable to collect data on impact of migraine on physical functioning, to evaluate treatment benefit. CONCLUSIONS: The impact of migraine includes impairments in functioning during and between migraine attacks that vary considerably on a daily basis. There is a need for novel PRO instruments that reflect patients' migraine experience to assess treatment benefit of migraine prophylactics. These instruments must evaluate the concepts identified and be able to capture the variability of patients' experience.

Perceived health status and cardiometabolic risk among a sample of youth in Mexico.

PURPOSE: To examine differences in self-reported perceived mental and physical health status, as well as known cardiometabolic risk factors in a sample of normal weight, overweight, and obese Mexican youths. METHODS: Cross-sectional analysis of 164 youths aged 11-18 years recruited in Cuernavaca, Mexico. Participants completed a self-administered questionnaire that included measures of generic and weight-specific quality of life, perceived health, physical function, depressive symptoms, and body shape satisfaction. Height, weight, and waist circumference were measured, and body mass index (BMI) was determined. Fasting blood samples from participants yielded levels of glucose, triglycerides, and cholesterol (total, HDL, and LDL). RESULTS: Nearly 50 % of participants were female, 21 % had a normal BMI, 39 % were overweight, and 40 % were obese. Obese youths reported significantly lower measures of perceived health status (PHS) and showed an increase in cardiometabolic risk, compared with normal weight youths. Physical functioning, generic and weight-specific QoL were inversely associated with BMI, waist circumference, and glucose. Depressive symptoms were positively correlated with BMI, waist circumference, glucose levels, and HDL cholesterol. No correlation was found between PHS and cardiometabolic risk measures after controlling for BMI. CONCLUSIONS: In this sample of Mexican youths, obesity was associated with a significantly lower PHS and increased cardiometabolic risk.

Patient experience of medication administration and development of a Patient Experience and Preference Questionnaire (PEPQ) for patients with advanced or metastatic cancer.

Introduction: A better understanding of patient experience of intravenous (IV) or subcutaneous (SC) routes of administration is fundamental to providing optimal administration of medical therapies to oncology patients. The objective of this study was to examine patient experiences of IV and SC treatment with nivolumab and confirm the relevance of item concepts in the Patient Experience and Preference Questionnaire (PEPQ). The PEPQ is a clinical outcomes' assessment instrument developed to obtain patient-centric data and understand the experience with IV and SC treatment administration. Methods: Embedded qualitative interviews were conducted with a subset of participants from three treatment cohorts with metastatic non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), unresectable or advanced metastatic melanoma, hepatocellular carcinoma (HCC), or colorectal cancer (CRC) from the CA209-8KX clinical trial. Concept elicitation interviews were conducted within 14 days of the initial treatment cycle and patient experiences with IV and SC treatment administration were assessed. Concepts from interviews were mapped to the PEPQ version 1.0 questions to assess relevance and convergence of concepts. Results: Interviews were conducted with 43 trial participants from clinical sites opting to participate from six countries (Argentina, France, the Netherlands, Poland, Spain, and New Zealand). The mean age of sub-study participants was 66 ± 11.3 years (range 24-80 years), and 67.4% (N = 29) were male. Sub-study participants with experience of SC most frequently reported symptoms or signs of injection-related redness (27.9%), itching (14.0%), and pain (of needle), and described the pain as pricking, stinging, or tingling (11.0% each). The amount of pain and time burden were widely endorsed as important factors for satisfaction and related to the route of medication administration. For 11 sub-study participants with experience with both IV and SC treatments, 10 (90.9%) preferred SC over IV treatment administration. Conclusion: This study summarizes the experience and satisfaction of receiving IV or SC treatment and confirms the relevance of the PEPQ in a subgroup of CA209-8KX clinical trial participants with metastatic NSCLC, RCC, melanoma, HCC, and CRC. Participant treatment experience and satisfaction with the route of medication mapped to the PEPQ question content support the relevance of PEPQ v2.0 in clinical trials as a self-report measure.

School placement and perceived quality of life in youth who are deaf or hard of hearing.

In the education of students who are deaf and hard of hearing (DHH), there is much debate about how placement affects educational outcomes and quality of life. This study examined the relationship between quality of life and educational placement that include and do not include other DHH youth. Participants included 221 DHH youth, ages 11-18 with bilateral hearing loss. Results showed that there were few differences in quality of life related to school placement (with age, gender, depression symptoms, and hearing level as covariates). For both participation and perceived stigma, there was an interaction between school placement and parent hearing status, with no single school placement showing the best results. DHH youth with hearing parents in schools specifically for DHH students scored lower than DHH with deaf parents in some domains (Participation and Perceived Stigma). When the DHH youth were compared with the general population, those in schools that included DHH students scored lower in some aspects of quality of life, particularly Self and Relationships. This study demonstrates that DHH students may not differ much in terms of quality of life across schools placements, but that there may be differences in subsets of DHH youth.

The Severity of Chronic Cough Diary (SCCD): development and content validation of a novel patient-reported outcome instrument for evaluating the symptom experience of chronic cough.

BACKGROUND: Refractory chronic cough (RCC), a cough lasting longer than 8 weeks with an unexplained underlying etiology and unresponsive to conventional treatment, can have substantial effects on patients' quality of life. For assessment of the efficacy of antitussive medication in clinical trials in RCC, patient-reported outcome (PRO) instruments should be fit for purpose with appropriate content validity. Here we describe the qualitative testing of a newly developed PRO instrument: the Severity of Chronic Cough Diary (SCCD). METHODS: The SCCD was developed to assess patients' symptom experience of cough in patients with RCC. A preliminary version was tested and refined based on an iterative process in a qualitative study. In total, three rounds of interviews were conducted with adult participants diagnosed with RCC in the USA (n = 19) and UK (n = 10). Rounds 1-3 consisted of hybrid concept elicitation (CE) interviews and cognitive interviews (CIs), with Round 3 also including interviews in a subset of participants (n = 5) about the usability of the SCCD as administered on an electronic handheld device. RESULTS: The CE interviews identified concepts important to patients' experiences related to RCC that were broadly in line with the concepts in the preliminary version of the SCCD. Participants provided positive feedback on the draft SCCD across all CI rounds, reporting the instrument to be relevant and straightforward to complete, and containing a comprehensive set of concepts to evaluate their symptom experience of RCC. Participants demonstrated a good understanding of proposed item wording, response options, and the 24-hour recall period, and thought completion of the SCCD on the electronic device was easy. Following revisions based on results from each interview round, the SCCD at the end of this qualitative research study had 14 items assessing the concepts of: cough symptoms (five items), symptoms related to cough (four items), disruption to activities due to cough (three items), and disruption to sleep due to cough (two items). CONCLUSIONS: The results of this study provide qualitative evidence supporting the content validity of the SCCD as a PRO instrument for evaluating outcomes of therapies for RCC in clinical trials.

Perceived body shape, standardized body-mass index, and weight-specific quality of life of African-American, Caucasian, and Mexican-American adolescents.

PURPOSE: To examine associations among perceived body shape, standardized body-mass index (zBMI), and weight-specific quality of life in African-American, Caucasian, and Mexican-American adolescents, aged 11-18 years. METHODS: Self-report questionnaires were administered to 454 adolescents between 11 and 18 years of age, of whom 53% were females, 33% were Caucasians, 30% were African-Americans, and 37% were Mexican-Americans. Thirty-four percent had a healthy zBMI, 20% were overweight, and 46% were obese. RESULTS: In examining the adjusted R-square and R-square changes among stepwise regression models, the model with depressive symptoms (adjusted R-square = 0.34), perceived body shape (adjusted R-square = 0.49), and female sex (adjusted R-square = 0.53) appears to be the most parsimonious and explanatory model for these data. Race/ethnicity and age did not enter the equations, due to their significance levels being greater than the probability of removal (0.1). CONCLUSIONS: This study demonstrates the importance of including the perceptual measures of weight-specific quality of life and perceived body shape in studies of and interventions with overweight and obese adolescents. Including these perceptual measures may provide increased insight into the motivations and values of overweight and obese youth and thus be useful for designing more effective weight interventions.

Validation of the EQ-5D in a general population sample in urban China.

PURPOSE: To evaluate the reliability and validity of the EQ-5D in a general population sample in urban China. METHODS: Thousand and eight hundred respondents in 18 communities of Hangzhou, China were recruited by multi-stage stratified random sampling. Respondents self-administered a questionnaire including the EQ-5D, the SF-36, and demographic questions. Test-retest reliability at 2-week intervals was evaluated using Kappa coefficient, the intraclass correlation coefficient. The standard error of measurement (SEM) was used to indicate the absolute measurement error. Construct validity was established using convergent, discriminant, and known groups analyses. RESULTS: Complete data for all EQ-5D dimensions were available for 1,747 respondents (97%). Kappa values were from 0.35 to 1.0. The ICCs of test-retest reliability were 0.53 for the EQ-5D index score and 0.87 for the EQ VAS score. The SEM values were 0.13 (9.22% range) and 4.20 (4.20% range) for the EQ-5D index and EQ VAS scores, respectively. The Pearson's correlation coefficients between the EQ-5D and the SF-36 were stronger between comparable dimensions than those between less comparable dimensions, demonstrating convergent and discriminant evidence of construct validity. The Chinese EQ-5D distinguished well between known groups: respondents who reported poor general health and chronic diseases had worse HRQoL than those without. Older people, females, people widowed or divorced, and those with a lower socioeconomic status reported poorer HRQoL. Respondents reporting no problems on any EQ-5D dimension had better scores on the SF-36 summary scores than those reporting problems. CONCLUSIONS: The Chinese version of the EQ-5D demonstrated acceptable construct validity and fair to moderate levels of test-retest reliability in an urban general population in China.

Symptom Experience and Content Validity of the Psoriasis Symptom Scale (PSS) in Patients with Generalized Pustular Psoriasis (GPP).

INTRODUCTION: We sought to understand key symptoms of generalized pustular psoriasis (GPP) and to confirm the relevance to patients and content validity of the Psoriasis Symptom Scale (PSS) in GPP. METHODS: A targeted literature review and clinical expert interviews were conducted as background research. Patients were interviewed individually (involving concept elicitation and cognitive interviews), and a separate patient workshop was conducted to determine disease-specific symptoms of importance. RESULTS: Seven participants with moderate (n = 4), severe (n = 2), and mild (n = 1) GPP and clinician diagnosis were interviewed. During concept elicitation, all participants indicated that pustules may underlie other symptoms. Symptoms reported by all patients were pain, redness, itch, burning, and discomfort. The PSS symptoms of pain, itching, burning, and redness were reported by ≥ 86% of patients as most frequently experienced. Upon debriefing, the PSS was well understood. Relevance and importance of these symptoms was confirmed in the GPP patient workshop. CONCLUSION: Participant feedback found the PSS measure to be relevant and easy to understand. The symptoms included in the instrument, pain, redness, itch, and burning, were most frequently reported, important, and well understood by patients. Study results provided support for the content validity of the PSS for use as endpoints in GPP clinical trials.

Generalized pustular psoriasis (GPP) is a severe rare disease, including redness and boils that sometimes come with fever and other general symptoms. This study asked patients with GPP about their key symptoms, and whether the Psoriasis Symptom Scale (PSS) is relevant to them as patients. The PSS is a questionnaire with the symptoms pain, itching, burning, and redness. We searched the literature and interviewed clinical experts to guide the patient interviews. Patients were recruited through clinical sites and the National Psoriasis Foundation (NPF). The interviews discussed GPP symptoms and the PSS questionnaire. Patients with GPP were also asked about commonly experienced symptoms in a workshop. Most patients had moderate to severe GPP. Patients in both the interviews and workshop described experiencing pain, redness, itch, burning, and discomfort with their boils. During interviews, the patients said the PSS questionnaire was easy to understand. Patients in the workshop also found the PSS to be relevant and easy to understand. Patients agreed the symptoms in the PSS, pain, redness, itch, and burning, were common and important. Study results support the PSS for use with patients in clinical trials.

Development of the SMA independence scale-upper limb module (SMAIS-ULM): A novel scale for individuals with Type 2 and non-ambulant Type 3 SMA.

BACKGROUND: The amount of assistance required to perform daily activities for individuals with Type 2 and non-ambulant Type 3 spinal muscular atrophy (SMA) is often cited as meaningful for quality of life, and important to routinely assess. METHODS: The SMA Independence Scale (SMAIS), a patient-reported outcome measure for individuals with SMA aged ≥12 years, and an observer-reported outcome measure for caregivers of individuals aged ≥2 years, was developed and evaluated in two phases. In Phase 1, 30 draft items were developed following review of the literature. Semi-structured interviews were then conducted with individuals with SMA and caregivers to establish content validity, resulting in a 29-item measure. In Phase 2, classical test theory and Rasch measurement theory methods were used to examine the cross-sectional and longitudinal measurement performance of the SMAIS in two independent datasets. RESULTS: Phase 1 qualitative findings supported the relevance, acceptability, and comprehensibility of 29 items. In Phase 2, psychometric analyses indicated that the five response options were poorly discriminated and were thus collapsed to three options for subsequent analyses. Items showed statistical misfit, implying that the SMAIS was not assessing a single underlying construct. Based on conceptual evaluation of the items, and assessment of item performance, a more targeted 22-item upper limb score was derived. Reliability and validity analyses confirmed acceptable measurement properties of this score. CONCLUSIONS: Qualitative and quantitative analyses support the use of the 22-item SMAIS-Upper Limb Module in individuals with Type 2 and non-ambulant Type 3 SMA, aged ≥2 years.

Development and content validation of the Satisfaction and Experience Questionnaire for Granulocyte Colony-Stimulating Factor (SEQ-G-CSF).

BACKGROUND: Several options for granulocyte colony-stimulating factor (G-CSF) prophylaxis of chemotherapy-induced febrile neutropenia are available to patients worldwide. We have developed a novel patient-reported outcome measure, the Satisfaction and Experience Questionnaire for G-CSF (SEQ-G-CSF), to help understand patients' perspectives of and satisfaction with different G-CSF options. RESULTS: Three oncology nurses and 40 adult oncology patients in the United States were enrolled and participated in focus group discussions to develop and refine the SEQ-G-CSF. Nurses had ≥ 5 years of experience treating oncology patients and were currently involved in the management of oncology patients receiving G-CSF prophylaxis. The patients had breast cancer, lung cancer, non-Hodgkin lymphoma, or prostate cancer (10 patients in each group) and were receiving G-CSF prophylaxis via injection or the on-body injector (OBI) device. The preliminary SEQ-G-CSF contained an item relevance questionnaire and three SEQ modules (sociodemographic, medical history, and G-CSF-related healthcare characteristics questionnaires). Twenty-one patients (53% of total sample size) discussed their experience and satisfaction with G-CSF. Their most common experiences were G-CSF effectiveness, convenience and benefits of the OBI, and relationships with healthcare providers. Side effects and having to undergo additional treatment were also reported. Satisfaction with aspects of G-CSF included the OBI and effectiveness of G-CSF treatment; dissatisfaction included inconvenience (having to return to the clinic the next day and administration of the injection) and the insurance approval process. The SEQ-G-CSF was finalized after three rounds of cognitive interviews and includes five domains related to general satisfaction (one item), treatment burden (four items), travel burden (two items), time burden (four items), and treatment compliance (two items). CONCLUSIONS: The SEQ-G-CSF is a novel instrument that quantifies a patient's experience and satisfaction with different G-CSF options using 13 easy-to-understand items. This study provides evidence for the content validity of SEQ-G-CSF. Although further psychometric testing is required, the SEQ-G-CSF may be a useful addition to clinical trials, observational studies, and clinical practice.

Measuring health-related quality of life in patients with rare disease.

BACKGROUND: There has been a growing emphasis on health-related quality of life (HRQoL) as an important outcome in rare disease drug development, although its assessment may be useful outside the drug development context, including in clinical applications or natural history studies. Central to assessing quality of life in health research is utilizing outcome measures that capture symptoms and impacts of the disease and treatment that are important and relevant to patients. Identifying and implementing valid and reliable tools to measure HRQoL in rare diseases poses unique challenges that often require creative solutions. MAIN BODY: In this commentary, we explore some of the challenges in HRQoL assessment in rare disease, propose solutions, and consider regulatory issues. Some of the solutions discussed entail the use of item banks, adapting existing measures from phenotypically similar disease contexts, use of multi-domain measurement indices, and adapting methods for assessing content validity of existing measures. Current regulatory considerations are discussed and resources outlined. CONCLUSION: Quality of life may be the most important endpoint for patients with rare diseases, and the challenges of valid assessment require effort and innovative thinking specific to each context to improve measurement and clinical outcomes.

A non-interventional observational study to identify and validate clinical outcome assessments for adults with phenylketonuria for use in clinical trials.

INTRODUCTION: Current clinical outcome assessments (COAs) are not effectively capturing the complex array of symptoms of adults with phenylketonuria (PKU). This study aimed to identify concepts of interest relevant to adults with PKU. Based on these concepts, COAs for patient-reported outcomes (PROs), observer-reported outcomes (ObsROs), and clinician-reported outcomes (ClinROs) were selected or developed and content validity was assessed. MATERIALS AND METHODS: Concept-elicitation interviews were conducted with an international cohort of adults with PKU (n = 30), family member observers (n = 14), and clinical experts (n = 8). Observers and clinical experts were included to overcome the risk of lack of self-awareness among adults with PKU. The concepts of interests endorsed by ≥30% of patients, observers, and/or clinical experts were selected, mapped to items in existing COAs, and used to develop global impression items for patients, observers, and clinicians. Next, the content validity of the COAs and global impression items was evaluated by cognitive interviews with patients (n = 22), observers (n = 11), and clinical experts (n = 8). All patients were categorized according to blood phenylalanine (Phe) levels (i.e., <600 µmol/L, 600-1200 µmol/L, and >1200 µmol/L). RESULTS: Concepts of interests were identified across four domains: emotional, cognitive, physical, and behavioral. After mapping, eight existing COAs were selected based on the concept coverage (six PROs, one ObsRO, and one ClinRO). The six PRO measures were considered as potentially fit-for-purpose. The ObsRO measure was not deemed relevant for use in observers of adults with PKU and only a subscale of the ClinRO measure was considered valid for assessing adults with PKU by clinicians. Due to the lack of existing COAs covering all concepts of interests, global impression items for symptom severity and change in symptoms were developed, which were limited to one question covering in total 14 concepts. Upon validation, some of the patient and observer global impression items were excluded as they were subject to lack of insight or could not be reported by observers. Due to the limited interaction time between clinician and patient, use of the clinician global impression items was not supported. CONCLUSION: Existing COAs relevant to adults with PKU were selected and PKU-specific global impression items were developed by mapping the most frequently identified concepts of interests from internationally-conducted in-depth interviews. Future studies should address the appropriateness of the selected COAs and global impression items to assess if these can be used as efficacy endpoints in PKU clinical trials.

Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications.

INTRODUCTION: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. METHODS: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts' clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). RESULTS: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). CONCLUSIONS: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.