Although cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, research describing the patient experience is limited. This study sought to create a conceptual model of non-metastatic disease, to assess patient-reported outcome (PRO) instruments commonly used in CSCC against this model, and to develop a patient-relevant measurement strategy for evaluating the benefit of new therapies. Researchers conducted a literature review, a review of patient blogs, and interviews with dermatologists to draft the conceptual model. A total of 22 patients with CSCC participated in 60-min phone interviews, which were subsequently transcribed, coded, and analyzed; the conceptual model was then updated. PRO instruments used in CSCC were assessed for content validity on the basis of this. The CSCC patient experience includes physical symptoms, psychological impacts, and behavior changes. Existing PRO instruments were assessed against the conceptual model using targeted subdomains considered to be relevant for assessing clinical benefit. Four modules of the FACE-Q® Skin Cancer instrument, plus de novo items developed for concepts not assessed by the FACE-Q® [lesion symptoms, negative treatment effects (including symptomatic), and experience of care], provide the best coverage for the concepts of interest hypothesized to show the benefit of novel treatments. This research provides a comprehensive understanding of the experience of patients with non-metastatic CSCC, and the effects of its treatment. It also identifies unmet needs in a subgroup of patients reporting negative treatment experiences. Further cognitive debriefing and psychometric analysis of de novo items are warranted for applications in clinical research.

**Background:** People living with hemophilia A face challenges impacting their daily lives despite treatment innovations. Previous studies have explored perceptions and treatment experiences; however, there is a lack of an evidence-based, comprehensive model to identify concepts (clinical, physical, and psychological functioning) relevant for people with hemophilia A (PwHA). **Objectives:** The aim of this qualitative study was to address the question: What is the humanistic and symptomatic experience of adolescents, adults, and children living with hemophilia A and what is the impact of hemophilia A on their quality of life? **Methods:** Participants, identified through patient associations in the UK, were male PwHA and caregivers of male PwHA receiving prophylactic treatment. Qualitative research was conducted involving semistructured telephone interviews with PwHA and caregivers between April 2020 and September 2020 in the UK. Standard analytical techniques of conceptual model development were used. **Results:** Of 30 participants, 23 were PwHA and 7 were caregivers. A conceptual model was produced describing patient experience of symptoms, physical functioning, treatment experiences, and the impact of symptoms and treatment on daily lives. Participants reported hemophilia-related symptoms, including bleeding, pain, and joint stiffness, as well as difficulties engaging with social and leisure activities. They also reported protection from bleeds provided by their treatment, relief from symptoms, and the resultant sense of normality. Concepts were broadly relevant across all age groups; however, psychological impacts were reported only by adult PwHA, and caregivers reported impacts related to outdoor activities, play, and education. Participants indicated that their ideal treatment would be delivered orally. **Discussion:** This study highlights the range of symptoms experienced by PwHA across a broad range of age groups, thus enabling the evaluation of relevant concepts across different stages of life. The research supports development of a conceptual model documenting symptoms, impacts, and treatment experience relevant to PwHA. **Conclusion:** Insights gathered through the interviews and resulting conceptual model support development of new therapies to address the physical and social challenges identified by PwHA and highlight a need for novel hemophilia A treatments that can ease treatment administration, provide adequate level of protection, and enable life to be lived normally.

INTRODUCTION:Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves.METHODS:This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit.RESULTS:Concept elicitation interview data from 26 participants with SCLC were used to develop a conceptual model of clinical treatment benefit that organized 28 patient-reported concepts into two domains: disease-related symptoms (organ-specific and systemic) and impacts. Organ-specific symptoms included cough, chest pain, and difficulty breathing. Systemic symptoms included pain, fatigue, appetite loss, and dizziness. Impacts included physical functioning, role functioning, reduced movement, impact on sleep, and weight loss.CONCLUSION:As evidenced by this study, people with SCLC experience considerable and significant symptoms and impacts, including physical and role functioning challenges, that affect their quality of life. This conceptual model will inform the design of a patient-reported outcome (PRO) questionnaire for a future SCLC clinical trial, helping to establish the content validity of the items and questionnaires used in the trial and ensuring that the questionnaires and items selected are appropriately targeted to the population. This conceptual model could also be used to inform future SCLC clinical trials.

Introduction: Following a review of patient-reported outcome (PRO) instruments in the literature, existing PRO instruments may not adequately capture the experience of receiving treatment for proliferative diabetic retinopathy (PDR). Therefore, this study aimed to develop a de novo instrument to comprehensively assess the patient experience of PDR. Methods: This qualitative, mixed-methods study comprised item generation for the Diabetic Retinopathy-Patient Experience Questionnaire (DR-PEQ), content validation in patients with PDR, and preliminary Rasch measurement theory (RMT) analyses. Adult patients with diabetes mellitus and PDR who received aflibercept and/or panretinal photocoagulation within 6 months of study initiation were eligible for participation. The preliminary DR-PEQ comprised four scales: Daily Activities, Emotional Impact, Social Impact, and Vision Problems. DR-PEQ items were generated using existing knowledge of patient experiences in PDR and conceptual gaps identified from existing PRO instruments. Patients indicated the level of difficulty conducting daily activities and frequency experiencing emotional impacts, social impacts, and vision problems attributed to diabetic retinopathy and its treatment in the past 7 days. Content validity was evaluated in two rounds of in-depth, semi-structured patient interviews. Measurement properties were investigated via RMT analyses. Results: The preliminary DR-PEQ comprised 72 items. Overall, mean (SD) patient age was 53.7 (14.7) years. Forty patients completed the first interview; of these, 30 completed the second interview. Patients reported that the DR-PEQ was easily understood and relevant to their experience. Minor revisions, including removal of the Social Impact scale and addition of a Treatment Experience scale, were implemented to generate 85 items spanning four scales: Daily Activities, Emotional Impact, Vision Problems, and Treatment Experience. RMT analyses provided preliminary evidence that the DR-PEQ performed as intended. Conclusion: The DR-PEQ evaluated a broad spectrum of symptoms, functional impacts, and treatment experiences relevant to patients with PDR. Additional analyses are warranted to evaluate psychometric properties in a larger patient population.

Objectives There is little in-depth qualitative evidence of how symptoms manifest themselves in outpatients with COVID-19 and how these in turn impact outpatients’ daily lives. The objective of the study was therefore to explore the experience of outpatients with COVID-19 qualitatively, concerning the symptomatic experience and its subsequent impact on daily life. Setting Qualitative research study comprising virtual in-depth, open-ended interviews with outpatients and clinicians. Participants Thirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. Patients were 60% female and 87% white, who had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Five independent clinicians were also interviewed about their experience treating outpatients. Primary and secondary outcome measures Transcripts were analysed thematically to organise symptoms and impacts of daily life into higher-order overarching categories, and subsequently propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis. Results Patient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, and physical, emotional, professional and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied by patient. Clinicians endorsed all patient-reported symptoms. Conclusions The manifestation of symptoms in outpatients is heterogeneous and affects all aspects of daily life. Outpatients offered new detailed insights into their symptomatic experiences, including heterogeneous experiences of smell and taste, and the impacts that symptoms had on their daily lives. Findings of this research may be used to supplement existing knowledge of the outpatient experience of mild-to-moderate COVID-19, to further inform treatment guidelines and to provide an evidence base for evaluating potential treatment benefits.

Introduction Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents’ perspectives. Methods We conducted a qualitative research study comprising in-depth, open-ended interviews with children and adolescents with FOP and their parents. Semi-structured interviews were conducted via phone call or Microsoft Teams with parent-child dyads ( n = 11), adolescents ( n = 6), and two clinicians. Children/adolescents and their parents were asked open-ended questions to elicit their daily experience of FOP. Results Concepts were organized into two major themes: symptoms of FOP and the impact of FOP on daily life. Symptoms of FOP reported by children/adolescents, parents, and clinicians were pain, swelling, redness, and stiffness. Functional impacts of flares and FOP in general included accommodations, mobility, activities of daily living, daily activities, and social activities. Impacts were attributed to the difficulties children and adolescents faced living with a disease that prohibited common activities. Conclusions This research documented the experience of children and adolescents with FOP and its effects on their daily lives. It provides a conceptual model for further exploration of the symptoms and impacts important to children and adolescents with FOP and their parents. Children and adolescents and their parents offered novel insights into life with the disease that have not previously been discussed in published literature. Future studies should build upon our conceptual model to create a holistic view of the patient experience of FOP, to inform clinical practice, and the assessment of the patient experience in clinical trials for the disease.

Introduction: Few qualitative studies have explored the patient experience of daily life with proliferative diabetic retinopathy (PDR) and associated treatments. Herein, a conceptual model was developed to comprehensively examine symptoms, functional impacts, and treatment experiences in PDR.Methods: A qualitative, mixed-methods study comprising a literature search and semi-structured interviews with clinicians and patients was conducted. Published literature and online patient resources were searched to identify concepts relevant to patients, including symptoms, functional impacts, and treatment experiences of PDR. Semi-structured interviews with experienced clinicians were conducted to identify symptoms and impacts reported by patients with PDR and to receive feedback regarding concepts identified from the literature search. A preliminary conceptual model was then developed based on findings from the literature search and clinician interviews. Patients with PDR participated in two rounds of semi-structured interviews to identify additional concepts relevant to the patient experience in PDR and associated treatments, which informed revisions to the conceptual model. Saturation of patient interviews was assessed.Results: Findings from the literature search and clinician interviews yielded 109 concepts that were included in a preliminary conceptual model with three overarching domains: symptoms, impacts, and managing the disease. Clinicians confirmed concepts identified from the literature search. During interviews, patients reported a broad spectrum of symptoms (e.g., red vision); functional impacts relating to activities of daily living (e.g., reading), emotional functioning (e.g., loss of independence), and social functioning (e.g., problems recognizing faces); and treatment experiences (e.g., improves eye problems, no change) associated with PDR. Additional concepts elicited in patient interviews informed revisions to the conceptual model. Saturation was achieved in the patient sample.Conclusions: A wide variety of symptoms, functional impacts, and treatment experiences that significantly affect health-related quality of life were identified in patients with PDR. These insights are critical for understanding PDR symptomology and assessing treatment response.

Introduction: Patient-centered outcome measurement (PCOM) is essential to capture the outcomes important to patients. However, it presents unique challenges in rare diseases, particularly those that are "young" (not diagnosed before the twenty-first century), with limited literature, lack of disease-specific patient-reported outcome (PRO) measures, and difficult sampling and data collection. One example of this is NUT (nuclear protein in testis) carcinoma (NUTca), a rare and rapidly progressing cancer, with tumors preliminary in the head, neck, and lungs. The published literature on NUTca is scarce. The limited number of case reports focus primarily on the clinical development and presentation of tumors. Currently, there are no publications describing the patient experience of NUTca and no specific PRO measures to assess the patient experience. We conducted mixed-methods research, including concept elicitation interviews, cognitive debriefing, and quantitative data analyses, to fill this evidence gap and describe challenges and solutions in the context of NUTca. Methods: As published previously, our conceptualization of NUTca was based on elicitation interviews with 27 participants (n = 10 patients; n = 17 caregivers) using a semi-structured format; this framework formed the basis for a bolt-on strategy to develop a bespoke PRO measure based on the EORTC QLQ-C30, supplemented by targeted items from the EORTC Item Library and new items. In this publication, 20 participants were interviewed (n = 10 patients; n = 10 caregivers) to debrief items. Given the variety of tumor locations and related symptoms, and the small sample of patients providing responses to location-specific symptom items, we used response option endorsement frequencies to illuminate the variability of response for the concepts measured. Results: This study highlights the challenges in implementing patient-centric research to inform and develop PRO measures in rare diseases. Conclusions: Our mixed-methods research used pragmatic solutions to collect patient experience data and provides an evidence base to inform PCOM in clinical programs in this rapidly progressing rare cancer with high unmet need.

Introduction Fatigue is one of the most important symptoms reported by patients with systemic lupus erythematosus (SLE) and a key concept of interest in SLE clinical trials. Despite this, fatigue remains poorly understood and sub-optimally measured by existing patient-reported outcome (PRO) instruments and scales. Here, we psychometrically evaluated the measurement properties of three PRO scales that purport to measure fatigue, using data from two SLE clinical trials. Methods Data were pooled from two completed phase 3 SLE trials: EMBODY1 (NCT01262365) and EMBODY2 (NCT01261793). FACIT-F, SF-36 Vitality and LupusQoL Fatigue data were selected for post hoc Rasch Measurement Theory psychometric analysis in two stages: (1) scale-to-sample targeting, thresholds for item response options, item fit statistics, and reliability; and (2) proposal and evaluation of pooled fatigue items based on the best-performing items. Responsiveness analyses on group-level (two effect size [ES] calculations and relative efficiency) and individual level (within person statistically significant difference), were conducted to compare original scales and pooled item sets. Results Scale-to-sample targeting was good for FACIT-F, but suboptimal for SF-36 Vitality and LupusQoL Fatigue. Thresholds for item response options were ordered for all three scales. Item misfit was found in all three scales (FACIT-F 10/13; SF-36 Vitality 4/4; LupusQoL Fatigue 1/4). Reliability statistics were good for FACIT-F (0.93) and LupusQoL Fatigue (0.80) but low for SF-36 Vitality (0.53). The pooled fatigue items improved some psychometric properties despite persisting misfit issues (2/10) and were more sensitive in detecting change at week 24 compared with un-pooled data (ES 0.41 vs. 0.26-0.25). Conclusions FACIT-F, SF-36 Vitality, and LupusQoL Fatigue were found to have important limitations in the EMBODY1 and EMBODY2 SLE clinical trials. Findings from pooled fatigue items support the need for further research to improve conceptual underpinnings of fatigue PROs and make them fit for purpose for drug development.

Introduction: NUT (nuclear protein of the testis) carcinoma (NUTca) is a rare and aggressive cancer that is genetically hallmarked by a chromosomal abnormality in the NUT gene, and presents with tumors in the head, neck, and lungs. Currently there is no standard of care, but patients may undergo surgery, radiation, and/or chemotherapy. There is a lack of published research describing the patient experience of NUTca. The objective of this study was to develop a conceptual framework (CF) that describes patients' experience of NUTca to inform the selection of outcome measures and design of patient-centric endpoints for future clinical research. Methods: Individual, semi-structured telephone interviews were conducted with patients and caregivers of patients who have/had NUTca (caregivers interviewed due to recruitment challenges resulting from the rarity of NUTca). Participants were asked about their disease symptoms, impacts, and treatment experience. Interviews were audio-recorded, transcribed, and analyzed using inductive coding. The CF was developed through inductive categorization of concepts, sub-domains, and domains. Results: Twenty-seven interviews were completed (patients n = 10; caregivers n = 17). Participants reported systemic symptoms (e.g., fatigue) and symptoms related to the location of the tumor (e.g., nose blockage for head/neck tumor). Pain emerged as an important and bothersome symptom across tumor locations. Participants reported impacts on their daily activities (e.g., showering), emotions (e.g., preoccupation), sleep, social life (e.g., isolation), roles (e.g., caring for children), and finances. The final CF was organized into four symptom domains [systemic, location-specific (head/neck, lung), pain, and digestive] and six impact domains (daily activities, emotional, sleep, social, role, and financial). Conclusions: This study describes the patient experience of NUTca and proposes an evidence-based CF that informs both the clinical community's understanding of the disease and selection of a patient-reported outcome (PRO) measure to assess treatment benefit in future NUTca trials.

SummaryBackgroundCoronavirus disease 2019 (COVID-19) is an acute respiratory illness characterised by a range of symptoms. Severe cases of COVID-19 could lead to hospitalisation and intensive care unit admission. However, little is known about the symptomatic experience of outpatients with COVID-19, or its daily life impact; the objective of this qualitative research was to document this experience.MethodsThirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. To be included, patients had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Patients were asked open-ended questions to elicit their symptoms and the impacts COVID-19 had on their daily lives. Interviews were transcribed and inductively coded to perform thematic analysis and propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis. Five independent clinicians were also interviewed about their experience treating outpatients with COVID-19.FindingsPatient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, physical impacts, emotional impacts, professional impacts and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied greatly by patient. Clinicians endorsed all symptoms reported by patients.InterpretationThe manifestation of symptoms in outpatient COVID-19 is heterogeneous and affects all aspects of daily life. While reported symptoms were in line with previously published reports, patients offered new detailed insights into their symptomatic experiences and the impacts that symptoms had on their daily lives. Future studies should explore the symptoms and impacts of COVID-19 longitudinally, to better understand their early onset, their progression/resolution and the possible long-term implications of COVID-19.FundingThis research was sponsored and paid for by Regeneron Pharmaceuticals, Inc.Research in contextEvidence before this studyDatabases used: PubMed. Criteria for inclusion: qualitative study of the outpatient experience of COVID-19 (December 2019 – March 2021). Search terms included “qualitative” OR “interviews” AND “COVID-19” or “coronavirus”. The quality of the evidence was deemed not relevant to the current study, as the work was related to other contexts (eg, hospitalized patients or treatment of COVID-19), or data was collected quantitively (ie, questionnaire/survey) and did not include an in-depth perspective of the outpatient experience.Added value of this studyThis research fills important gaps in the literature, as the outpatient experience (ie, symptoms and daily life impacts) of COVID-19 has not been documented qualitatively.Implications of all the available evidenceFindings of this research may be used to supplement existing knowledge of the outpatient experience of mild-to-moderate COVID-19, to further inform treatment guidelines. This work also provides an evidence base for identifying the symptoms and impacts important for evaluating potential treatment benefit in outpatients.

Purpose Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library. Methods The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated. Results The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe). Conclusion The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML.