BackgroundUlcerative colitis (UC) often first presents during adolescence and early adulthood. Primary symptoms of UC are well known, yet similarities and differences of disease experience in adults and adolescents are not well characterized.MethodsTo understand the health-related quality of life (HRQoL) and symptomatic experience of UC, in-depth interviews were conducted in the US with 21 adults (20–70 years) and 14 adolescents (12–17 years). Eligibility and medical history were confirmed by clinician report. A previously conducted literature review and resultant conceptual model informed the discussion guide to explore symptoms and HRQoL. Age appropriate creative tasks (“animal” task and collage) were employed to facilitate discussion. Transcripts and collages were subjected to thematic analysis using ATLAS.ti software.ResultsClinician-reported UC severity included 24% mild, 38% moderate, 38% severe among adults; and 64% mild, 29% moderate, 7% severe among adolescents. Among adults, 52% were female, 67% were white. Among adolescents, 50% were female, 71% were white. During analysis it was noted that all participants reported stomach/abdominal pain. Other key symptoms identified were frequent bowel movements, diarrhea, blood in stools, sudden need for bowel movement, stomach cramping, bloating, and feeling gassy/passing gas (≥75% of participants). Key impacts identified were embarrassment, dietary limitations, having to plan around UC, worry/fear, anger, low mood/depression, and relationship with others, (≥75% of participants). In creative tasks, animals were chosen to represent their UC and content included in the collages reflected the most commonly discussed themes from the interviews. Only adults discussed feeling dehydrated, while only adolescents discussed the impact of UC on school life.ConclusionsOpen-ended interviews highlighted the HRQoL and symptomatic experiences of UC from the patient’s perspective, which were similar between adult and adolescent UC patients.

Background Patient-reported outcome measures (PROs) used to measure symptoms of patients with paroxysmal nocturnal hemoglobinuria (PNH) in trials do not measure PNH symptoms comprehensively and do not assess daily fluctuations in symptoms. Following a literature review and consultation with a PNH expert, we drafted the PNH Symptom Questionnaire (PNH-SQ) and a patient-centric conceptual model of PNH symptoms and impacts. We then interviewed 15 patients with PNH to assess comprehensiveness of symptom capture from the patient perspective and to cognitively debrief the PNH-SQ. Patient interview data were also used to finalize the PNH conceptual model. Results Participants mentioned 27 signs or symptoms of PNH spontaneously or after being probed; 93% reported experiencing ≥ 1 PNH symptom. Concept saturation was reached for all PNH symptoms. Further, interviews confirmed the instrument captured the most common PNH symptoms, including fatigue (87%), abdominal pain (60%), and difficulty swallowing (47%), with fatigue ranked as the most bothersome symptom. The interviews demonstrated that participants understood the items of the PNH-SQ (90–100%); considered the symptoms relevant (> 50– > 90%); the recall period appropriate (> 80–100%); and the response options suitable (> 80–100%). Participants also suggested changes regarding item redundancy and relevance; this feedback was used to finalize the instrument. Conclusions The finalized PNH-SQ assesses the presence and severity of 10 symptoms—abdominal pain, chest discomfort, difficulty sleeping, difficulty swallowing, difficulty thinking clearly, fatigue, headache, muscle weakness, pain in the legs or back, and shortness of breath—over 24 h. The PNH-SQ is a content-valid questionnaire suitable for assessing daily symptom presence and severity in PNH clinical trials.

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening blood disease. Frequently reported symptoms of PNH are fatigue, dyspnea, hemoglobinuria, abdominal pain, and chest pain. While PNH-related symptoms can impact quality of life, there are no patient-reported outcome (PRO) measures that assess daily occurrence and severity of PNH-specific symptoms. The objective of this study was to gain a deeper understanding of the patient experience related to symptoms of PNH, and to assess the content validity of the newly developed PNH Symptom Questionnaire (PNH-SQ). Methods. The content and design of the PNH-SQ was informed by a review of the empirical literature, review of COAs used in registrational PNH trials to assess symptoms and impacts of PNH, and through discussions with physicians who have experience treating patients with PNH. The first draft of the PNH-SQ allowed the patient to record, on a daily basis, the presence/absence of 12 symptoms in the past 24 hours (fatigue; shortness of breath; muscle weakness; headache; abdominal pain; leg/back pain; chest discomfort; sexual difficulties; difficulty sleeping; difficulty focusing; difficulty thinking clearly; difficulty swallowing), and the severity of each symptom using a 5-point Likert scale. Trained interviewers conducted telephone, video, or in-person qualitative, semi-structured 60-minute interviews with adult patients with a clinician-confirmed PNH diagnosis. The interviews consisted of two distinct parts: concept elicitation (CE), to assess whether the PNH-SQ captured all important symptoms from the perspective of the patient; and cognitive debriefing (CD), to evaluate the patient's ability to understand and respond to the PNH-SQ. During CE, participants discussed symptoms and impacts of PNH. This was followed by CD, in which participants reviewed and completed the PNH-SQ and asked about each part of the PNH-SQ including the instructions, understanding and relevance of items, recall period, and response options. Interviews were audio-recorded, transcribed, coded, and analyzed. Revisions to the PNH-SQ were considered after interviews were completed and analyzed. Results. A total of 15 participants (mean age of 42.8 years; 53.3% women) from across the United States were interviewed; participants had a mean of 13.4 years since PNH diagnosis, and 66.7%, 13.3%, and 20.0% self-reported very mild/mild, moderate, and severe/very severe PNH, respectively. In the CE part of the interview, participants reported experiencing fluctuations in the presence and/or severity of individual PNH symptoms. The most common symptoms mentioned were fatigue (n=13/15), abdominal pain (n=9/15), and difficulty swallowing (n=7/15). Symptoms spontaneously mentioned by at least 5 participants were: muscle weakness; back pain; cognitive difficulties; and shortness of breath. Fatigue was by far considered the most bothersome symptom (n=8/15); other symptoms had ≤3 mentions as most bothersome symptom. Each symptom included in the PNH-SQ was spontaneously mentioned by two or more participants. Concept saturation, the point at which no new or relevant information is expected to emerge from additional interviews, was reached. In the CD segment of the interview, participants demonstrated understanding of all the symptoms included in the PNH-SQ (90-100%); considered the symptoms relevant (>50 - >90%); the recall period appropriate (80-100%); and the response options suitable (>80-100%). Based on interview analysis, two items were removed from the PNH-SQ: sexual difficulties, because it was of limited relevance to most participants (2/15), and was reported mostly by men; and difficulty focusing, because most participants (n=9/15) considered it interchangeable with difficulty thinking clearly. Minor modifications were also made to accommodate electronic administration of the PNH-SQ. Conclusions. The PNH-SQ was developed according to FDA guidance on PRO measures development. Findings from this study support content validity of the PNH-SQ as an instrument to evaluate the daily presence and severity of PNH symptoms. In addition, the PNH-SQ has the potential to enable the evaluation of day-to-day fluctuations in PNH symptom presence and severity. The next step in instrument development is to conduct psychometric testing of the PNH-SQ using data from an ongoing clinical trial (NCT03946748). Disclosures Daly: Clinical Outcomes Solutions: Employment. Jalbert:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Keith:Clinical Outcomes Solutions: Employment. Symonds:Clinical Outcomes Solutions: Employment. Shammo:Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTI Pharma: Research Funding; Onconova: Research Funding; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Astex Pharma: Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau.

Background: Clinicians treating multiple sclerosis (MS) should consider patient preferences when making treatment decisions. An online mixed-methods approach to elicit patientcentered concepts, group concept mapping (GCM), was used to generate statements reflecting the patient experience in relapsing-remitting MS and identify the most important patient-centered outcomes from patient and clinician perspectives. Patients and Methods: Twenty patients and 12 MS specialists in the United States provided statements describing what an ideal treatment would do to improve symptoms and daily functioning. Statements were sorted by participants into meaningful domains and rated on importance on an 11-point scale.Results: Sixty-four unique statements supporting 6 domains of clustered concepts were generated. Patient and clinician ratings of importance were highly correlated (r=0.82); however, patients rated the domains of Activities of Daily Living, Prevent & Cure, and Address Symptoms as highest in importance, whereas clinicians rated Prevent & Cure, Safe & Effective, and Activities of Daily Living as highest in importance. Statements rated above the domain mean by both patients and clinicians included "Improve cognitive function" and "Improve motor function" in the Activities of Daily Living domain and "Help with memory issues" and "Help preserve cognition" in the Address Symptoms domain. The statement "Improve short term memory" was 1 of 3 statements rated above the domain mean by patients but below the domain mean by clinicians. Conclusion: High levels of agreement of concept importance were found between patients and MS specialists, although certain domains and statements were rated more highly by one group. Overall, concepts such as cognitive function, physical and emotional functioning, and activities of daily living were perceived as having great importance for treatment outcomes versus symptom-focused outcomes like gait or tingling sensations. This comprehensive concept model for the MS patient experience can be used for further development of patientcentered outcome measures in MS treatment.

4.3 (1.4) (1=never, 7=always); Product Avoidance scale 4.6 (1.1) (1=almost none, 7=almost all); and, Social Impact scale 3.9 (1.5) (1=negligibly small, 7=extremely great). High rates of PA-related healthcare use in the previous 12 months were reported: PA-related hospitalization (34.3%); scheduled (84.4%) and unscheduled (55.0%) allergist visit; PA-related general practitioner visit (62.8%); $1 EA injection (58.8%); emergency department/urgent care visit (56.9%); and over-the-counter medication for PA (65.7%). Conclusions: Despite currently available PA management approaches, adolescents have substantial concerns regarding their health risks and frequently require various forms of healthcare to deal with PA reactions. There remains an unmet need for an approved treatment that safely provides certainty of protection to alleviate the constant fear of accidental exposure.