Patient-Reported Outcome Measures for Severe Recurrent Bilateral Nasal Polyps: Psychometric Evaluation and Content Validity.

Objective: To date, no patient-reported outcome measures have been specifically developed to assess pharmacological treatment effect in participants with severe chronic rhinosinusitis (CRS) with recurrent bilateral nasal polyps (NP). These studies aimed to assess (1) the psychometric properties and (2) content validity of Visual Analogue Scales (VAS) assessing NP symptom severity. Study Design: (1) Retrospective psychometric validation study using clinical trial data and (2) cross-sectional qualitative patient interview study. Setting: (1) Multicentre trial; (2) real-world. Methods: (1) Psychometric validation was performed using data from a randomized, double-blind, placebo-controlled, Phase II study (NCT01362244) investigating the effect of mepolizumab in 105 participants with severe, recurrent bilateral NP currently needing polypectomy surgery. (2) Content validity was explored through cognitive debriefing interviews in 27 adults with severe CRS with recurrent bilateral NP who had received NP surgery in the past 10 years (NCT03221192). Results: (1) Acceptable reliability, validity, and responsiveness were shown for individual VAS items, although the loss of smell VAS item performed poorly in several analyses, suggesting further evaluation of this item is needed. (2) All individual VAS items were well understood, considered relevant and were consistently interpreted by most participants, providing evidence for their content validity. Conclusion: These findings support the use of symptom VAS measures to evaluate disease experience and treatment effect in clinical trials of participants with severe CRS with recurrent bilateral NP.

Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O).

BACKGROUND: Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium's Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary-Child (PAD-C) for children 8-11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD-O) for caregivers of children 4-11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O. METHODS: Semi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8-11 y.o. and 30 caregivers of children 4-11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications. RESULTS: Concept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item. CONCLUSIONS: Findings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures.

Pediatric asthma is one of the most common chronic diseases in children. However, there are problems of underdiagnosis, poor disease management, and undertreatment for many pediatric asthma patients, pressuring healthcare systems worldwide. Evaluating asthma symptoms is an important part of the development of treatments for pediatric asthma. However, there are few clinical outcome assessments (COAs) developed in line with regulatory guidance to directly assess symptom severity and evaluate the benefit of new treatments in children with asthma. In this study, we continued the development of the Pediatric Asthma Diary­Child (PAD-C) and the Pediatric Asthma Diary­Observer (PAD-O), according to regulatory guidance, to assess asthma signs and symptoms in children 4 through 11 years old and address this unmet need. The study aimed to explore the experience of pediatric asthma and assess how well-understood and relevant the measures are. Three rounds of qualitative interviews were conducted with 15 children 8 through 11 years old and 30 caregivers of children 4 through 11 years old with asthma. Results show that both measures are well-understood and assess the relevant and important aspects of pediatric asthma reported by children and caregivers. Findings provide evidence supporting the PAD-C and PAD-O as measures of symptom severity and their future use in pediatric asthma treatment trials. Further research is underway to evaluate their measurement properties and assess the user experience and feasibility of electronic completion, to ultimately support the PAD-C and PAD-O in an ongoing COA qualification process by the United States Food and Drug Administration.

A qualitative study to explore the symptoms and impacts of Crohn's disease and to develop the Crohn's Disease Diary.

PURPOSE: To explore symptoms and disease impacts of Crohn's disease and to develop a new patient-reported outcomes (PRO) measure according to industry best practices. METHODS: A conceptual model of relevant symptoms experienced by patients with Crohn's disease was developed following a literature review. Three rounds of combined qualitative semi-structured concept elicitation and cognitive debriefing interviews with 36 patients (≥ 16 years) with Crohn's disease and 4 clinicians were conducted to further explore the most commonly reported and most bothersome symptoms to patients. Interview results were used to update the conceptual model as well as items and response options included in The Crohn's Disease Diary, a new PRO measure. RESULTS: All patients (N = 36) reported abdominal pain, loose or liquid bowel movements, and high or increased frequency of bowel movements, with most reporting these symptoms spontaneously (100%, 92%, and 75%, respectively). All patients reported bowel movement urgency, but 61% reported this symptom only when probed. Most also reported that symptoms impacted activities of daily living, work/school, and emotional, social, and physical functioning (overall, 78%-100%; spontaneously, 79% - 92%). Data regarding core symptoms of Crohn's disease from clinician concept elicitation interviews supported patient data. The 17-item Crohn's Disease Diary assesses core symptoms and impacts of Crohn's disease over 24 h, and extraintestinal manifestations over 7 days. The content validity of the diary was confirmed during cognitive debriefing interviews. CONCLUSION: The Crohn's Disease Diary is a new PRO measure for the assessment of Crohn's disease symptoms and impacts, developed according to industry best practices.

Qualitative Research with Patients and Physicians to Assess Content Validity and Meaningful Change on ESSDAI and ESSPRI in Sjögren's.

INTRODUCTION: European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) is a clinician-reported outcome (ClinRO) instrument, assessing Sjögren's disease activity from the physician perspective. EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported outcome (PRO) instrument, assessing patient-defined Sjögren's symptom severity. Both instruments are commonly used as clinical trial endpoints and have been psychometrically validated. However, qualitative evidence supporting content validity and what constitutes a meaningful change is limited. Qualitative evidence supporting Physician/Patient Global Assessment of disease activity and symptom severity (PhGA/PaGA) items used within anchor-based analyses for ESSDAI/ESSPRI is also lacking. METHODS: Qualitative, semi-structured, telephone/video interviews were conducted with patients with Sjögren's (n = 12) and physicians who specialise in Sjögren's (n = 10). Interviews explored: appropriateness of ESSDAI domain weights and meaningful improvements on domain/total scores from the physician perspective, appropriateness of ESSPRI's 2-week recall period from the patient/physician perspective, patients' perspectives on meaningful improvements in ESSPRI total scores, and patients'/physicians' interpretation of PhGA/PaGA items. RESULTS: Most ESSDAI domain weights were considered clinically appropriate. Generally, a one-category improvement in domain-level scores and a 3-point improvement in total ESSDAI scores were considered clinically meaningful. Most patients/physicians considered ESSPRI's 2-week recall period appropriate, and patients considered a 1-to-2-point ESSPRI total score improvement meaningful. PhGA/PaGA items developed for use as ESSDAI/ESSPRI anchors were consistently interpreted. CONCLUSIONS: The findings support use of ESSDAI and ESSPRI as Sjögren's clinical trials endpoints, as well as in clinical practice and other research settings. Qualitative data exploring meaningful change supports existing minimal clinically important improvement (MCII) thresholds.

European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) is an assessment used by physicians to measure how active Sjögren's is in individuals with the condition. EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is a questionnaire completed by individuals with Sjögren's to assess the severity of their symptoms. It is important to show that ESSDAI and ESSPRI are considered appropriate by physicians and individuals with Sjögren's, respectively, and that ESSPRI is well understood by individuals with Sjögren's completing the questionnaire. Therefore, interviews were conducted with physicians who specialise in Sjögren's to explore the appropriateness of ESSDAI, the level of improvement on the assessment that would be important to individuals with Sjögren's, and the appropriateness of the ESSPRI recall period (i.e. whether it is acceptable to ask individuals to remember their symptoms over the past 2 weeks). Interviews were also conducted with individuals with Sjögren's to explore their understanding and relevance of ESSPRI (including the 2-week recall period) and the level of improvement on the questionnaire that would be important to them. Most physicians and patients considered ESSDAI and ESSPRI appropriate, supporting their use in a range of settings including Sjögren's clinical trials, clinical practice and other research settings. Most physicians reported that a 3-point improvement in ESSDAI total score would be meaningful to individuals with Sjögren's. Individuals with Sjögren's reported that a 1-to-2-point improvement in ESSPRI total score would be meaningful.

Generation of evidence supporting the content validity of SF-36, FACIT-F, and LupusQoL, and novel patient-reported symptom items for use in patients with systemic lupus erythematosus (SLE) and SLE with lupus nephritis (LN).

OBJECTIVE: SLE and lupus nephritis (LN) have significant impacts on the health-related quality of life of patients living with the condition, which are important to capture from the patient's perspective using patient-reported outcomes (PROs). The objectives of this study were to evaluate the content validity of PROs commonly used in SLE and LN (36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Lupus Quality of Life (LupusQoL), as well as novel PRO symptom severity items measuring skin rash, joint pain, joint stiffness and swelling of the legs and/or feet, in both populations. METHODS: Qualitative, semi-structured, cognitive interviews were conducted with 48 participants (SLE=28, LN=20). Understanding and relevance of symptom and impact PRO concepts from existing PROs were assessed, alongside novel PRO symptom severity items with different recall periods (24 hours vs 7 days) and response scales (Numerical Rating Scale (NRS) vs Verbal Rating Scale). Interviews were conducted in multiple rounds to allow for modifications to the novel PRO items. Analysis of verbatim interview transcripts was performed. RESULTS: Symptom and impact concepts assessed by the SF-36, FACIT-F, and LupusQoL were well understood by both participants with SLE and LN (≥90.0%), with most considered relevant by over half of the participants asked (≥51.9%). All participants asked (100%) understood the novel PRO symptom severity items, and the majority (≥90.0%) considered the symptoms relevant. Minor modifications to the novel PRO items were made between rounds to improve clarity based on participant feedback. The selected 7-day recall period and NRS in the final iteration of the PRO items were understood and relevant. No differences in interview findings between the SLE and LN samples were identified. CONCLUSIONS: Findings provide evidence of content validity for concepts assessed by the SF-36, FACIT-F, LupusQoL and the novel PRO symptom severity items, supporting use of these PROs to comprehensively assess disease impact in future SLE and LN clinical trials.

Qualitative evaluation of the symptoms and quality of life impacts of long-chain fatty acid oxidation disorders.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare autosomal-recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy. To date, however, there is limited understanding of the patient experience of LC-FAOD. METHODS: The symptoms, observable signs, and quality of life (QoL) impacts associated with LC-FAOD were explored via a focus group (n = 8) and semi-structured interviews (n = 6) with patients and caregivers of patients with LC-FAOD, and interviews (n = 4) with expert clinicians. Data were analyzed via thematic analysis and summarized in a conceptual model. RESULTS: Participants reported a wide range of signs and symptoms associated with LC-FAOD, broadly categorized as musculoskeletal, endocrine/nutritional/metabolic, neurological, gastrointestinal/digestive, sensory, cardiovascular, respiratory, urological, and constitutional. LC-FAOD were reported to have a significant impact on various aspects of patients' lives including physical functioning, participation in daily activities, emotional/psychological wellbeing, and social functioning. Lifestyle modifications (such as diet and exercise restrictions) were necessary because of the condition. Symptoms were typically episodic in presentation often arising or exacerbated during catabolic conditions such as prolonged exercise, fasting, physiological stress, and illness/infection. Symptoms were also commonly reported to lead to emergency room visits, hospitalization, and clinical complications. CONCLUSION: LC-FAOD have a considerable impact on patients' lives. There is a high degree of concordance in the signs, symptoms, and impacts of LC-FAOD reported by patients, caregivers, and clinicians; however, there were many symptoms and impacts that were only reported by patients and caregivers, thus demonstrating that insights from patient/caregiver experience data are integral for informing medical product development and facilitating patient-centered care.