Natalie Valerie Jane Aldhouse

Background/Objectives: Up to 95% of cancer patients report sleep disturbances or disorders. These can potentially influence cancer development and outcomes. This study aimed to review the existing literature to understand the patient experience of cancer-related sleep impairment across indications and treatments, to improve awareness and inform disease treatment/management. Methods: A targeted literature review of published qualitative studies exploring sleep impairment in oncology was conducted in MEDLINE, Embase, and PsycINFO. Concepts were extracted from the reviewed articles, and patient quotes or author descriptions/interpretations were subject to secondary analysis using semantic, qualitative, directed content analysis techniques via ATLAS.ti. Results informed the development of a patient-centric conceptual model. Results: From 482 identified publications, 22 publications were selected for in-depth review and concept extraction, collectively including 531 patients across 25 different oncology indications. Cancer-related sleep impairment frequently affected patients living with cancer, who reported difficulty obtaining good quality sleep, including difficulty falling asleep and staying asleep. Sleep problems were triggered by the emotional anxiety of life with cancer, cancer-related symptoms, treatments and side effects, and external factors. Poor sleep greatly impacted daily life for patients, with difficulties in daily life causing further sleep impairment, in a cyclical relationship. Conclusions: This study determined that there is an unmet need for treatment of sleep impairment in oncology to improve patient outcomes. The holistic conceptual model developed in this study can provide an important basis for selecting, developing, or modifying outcome measures to assess relevant sleep outcomes, facilitating discussion between patients and clinicians and improving disease treatment/management.

Background: Clinician-reported outcome measures (ClinROs) are completed by trained clinical experts, yet the signs and behaviors they capture must reflect meaningful aspects of health to patients. FDA Patient Focused Drug Development (PFDD) Guidance indicates the importance of establishing content validity for ClinROs. Patient and caregiver input can support the conceptual relevance of ClinROs and inform score interpretation such as meaningful change thresholds. Objective: To synthesize lessons learned from four qualitative case studies in which patient or caregiver input informed (1) ClinRO content validity and (2) within-patient clinically meaningful change thresholds, and to develop methodological recommendations for future studies. Methods: We reviewed four, purposively selected, qualitative studies designed to inform the development or validation of ClinROs. Contexts were varied across neurodegenerative and autoimmune conditions. Across studies, concept elicitation and cognitive debriefing interviews were conducted with patients or caregivers alongside clinical expert interviews. Visual aids and task adaptations were used to support participants’ comprehension of clinical terminology and inform scoring discussions. Results: We propose six methodological recommendations for incorporating patient/caregiver input during ClinRO development and validation. When gathering patient/caregiver input to inform content validity, researchers should: (1) frame the purpose; (2) use multimodal supports; (3) simplify scoring for the task; (4) map language. When developing an endpoint hierarchy researchers should align endpoints with patient priorities. When informing meaningful change thresholds, researchers should elicit discussion of patient perspective. The reviewed studies confirmed that patients and caregivers could generally understand and participate in interview tasks using visual aids provided. Conclusions: Incorporating patient/caregiver input during ClinRO development/validation strengthens content validity and provides qualitative insights into meaningful change thresholds to inform score interpretation. Practical techniques (advance framing, visual aids, simplified scoring) support patient/caregiver engagement with complex ClinROs. Methodological recommendations are provided for incorporating patient/caregiver input into ClinRO evidence generation to inform patient-focused clinical trial measurement strategies.

Introduction/Aims: The patient experience of Becker muscular dystrophy (BMD) is not well understood, making it difficult to evaluate the conceptual relevance of proposed patient‐reported outcome (PRO) measures. This study aimed to conceptualize the patient experience of BMD and evaluate content validity and perceptions of meaningful changes of PRO measures in this population. Methods: Semi‐structured interviews were conducted with ambulatory adult and adolescent US‐based participants with BMD. Transcripts were analyzed using content and framework analysis. Participant quotes were coded to identify concepts and themes, illustrated in a conceptual model of BMD experience. Cognitive debriefing methods assessed patient understanding of the brief pain inventory‐short form (BPI‐SF), quality of life in neurological disorders (Neuro‐QoL), and three patient‐reported outcomes measurement information system (PROMIS‐57) domains: Physical Function, Fatigue, and Pain Interference. Results: Twenty‐nine patients (mean age: 27.0 years; mean age at BMD diagnosis: 15.1 years) and two caregivers described a wide range of signs, symptoms, and impacts. Physical fatigue, pain, weakness, and impacts on physical mobility and emotional wellbeing were considered most bothersome. The BPI‐SF Item 3 and PROMIS‐57 domains were well understood and relevant; however, the Neuro‐QoL Upper Extremity questionnaire demonstrated low conceptual relevance. Discussion: The conceptual model illustrated the burden of living with BMD. The BPI‐SF Item 3 and evaluated PROMIS‐57 domains are considered content‐valid PRO measures in BMD, with most participants associating score improvements with meaningful changes to their health‐related quality of life.

Background and objective: Typical endpoints in cancer clinical trials focus on standardized efficacy endpoints, such as overall survival. Pain is not always assessed, although it is a highly prevalent and distressing aspect of patients’ cancer experience and plays a critical role in health-related quality of life. To inform future pain measurement strategies in oncology, this targeted literature review of pain-related qualitative publications in oncology aimed to characterize and explore the patient experience of pain, and its impact on how patients feel and function. Methods: A review of publications in MEDLINE, Embase and PsycINFO from 2018 to 2023 was conducted. Patient quotes or author descriptions/interpretations were extracted and analyzed with directed content analysis techniques, using ATLAS.ti v9. Data were synthesized to inform the development of a conceptual model. Results: Twenty-eight publications, with data from 534 patients across different oncology indications and geographies, were reviewed. Pain was triggered by disease symptoms and treatment, including surgical procedures, chemotherapy, and radiation. Pain was most often daily, severe, and chronic in nature. Characterizations of pain varied, but most often “sharp”/“stabbing”/“shooting” pain was described across different treatment stages. Pain had an extensive impact on emotional wellbeing, activities of daily living, physical, physiological and social functioning, sleep and work. Unmet needs included difficulty communicating pain needs to healthcare practitioners and fear/distrust of opioid pain medication. Conclusions: This research provides a patient-centric model conceptualizing the patient experience of cancer-related pain. The findings highlight the burden and all-encompassing impact of cancer-related pain, demonstrating the importance of assessing pain in oncology clinical trials.

Introduction Traditionally, treatment endpoints in oncology have focused on increasing overall survival and progression-free survival. Although fatigue may be a meaningful outcome measure across different cancers, it is assessed less frequently. To explore the impact of fatigue on patients with cancer, confirm the importance of fatigue measurement and inform future measurement strategies in oncology, we aimed to characterise the patient experience of fatigue and the associated impact on how patients feel and function, including aspects of health-related quality of life (HRQoL). Methods A targeted literature review of published fatigue-related qualitative publications in oncology was conducted in MEDLINE, Embase and PsycINFO, limited to studies published between 2018 and 2023. Concepts were extracted from the qualitative literature and patient quotes or author descriptions/interpretations were subject to secondary analysis using semantic, qualitative, directed content analysis techniques via ATLAS.ti v9. The literature review informed the development of a preliminary patient-centric conceptual model of fatigue in oncology. Results Of 1210 identified publications, 26 were selected for data extraction, including 512 patients living with 28 different oncology indications across geographies. Frequently reported fatigue triggers included treatments and cancer itself. Patients used various fatigue descriptors, including low/lack/loss of energy, tiredness and exhaustion, across disease stages. Physiological and cognitive manifestations of fatigue were reported, and fatigue episodes were described as unpredictable and of variable severity, duration and frequency. Cancer-related fatigue had a substantial negative effect on patients’ QoL, including emotional, physical, physiological, social, activities of daily living, sleep and work impacts. Unmet needs included poor support from healthcare professionals (HCPs). Conclusions This review demonstrated that fatigue is an impactful symptom across oncology indications and provides the first holistic conceptual model of cancer-related fatigue across disease stages and treatments. Future research should review clinical outcome assessments (COA) that may be fit-for-purpose for measuring fatigue in oncology clinical trials.

Background: Knee osteoarthritis (KOA) is a chronic degenerative condition. Pain is the most prominent symptom of KOA, which can be exacerbated by obesity. The US Food and Drug Administration recommends using patient‐reported outcome (PRO) measures to assess KOA pain and function in clinical trials, but none have been validated for patients with KOA and obesity/overweight. The objective of this study was to explore and document the patient experience of signs, symptoms, and health‐related quality of life (HRQoL) impacts of KOA pain, including the impact of obesity/overweight, to facilitate future validation studies. Methods: A targeted literature review and interviews with US participants with KOA pain (including some with comorbid obesity) were conducted. Publications and interview transcripts were analysed using content analysis methods to develop a conceptual model of KOA pain experience. Results: Eighteen publications were reviewed and 25 participants were interviewed. All participants in the interviews reported knee pain and described that their physical functioning had been negatively affected. Many experienced a negative emotional/psychological impact. Many participants believed that there was a relationship between their weight and experience of KOA pain, reporting a ‘vicious cycle’ of pain and weight gain due to KOA. Conclusions: This study highlights the burden of living with KOA pain and the negative impact of obesity/overweight on patients' HRQoL. A conceptual model was developed, which may be used to explore the content validity of PRO measures and promote a robust understanding of the patient experience of living with KOA pain during the development of new therapies.

Background Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs. Methods This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, ‘at-risk’ individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9–17 years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed. Results The sample was diverse; participants were 51% female, aged 20–57 years (mean 37 years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) [groupings are not mutually exclusive]. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile [98%], and vaccine efficacy [85%], cost [73%] and administration schedule [88%]); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the ‘at-risk’ group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine’s clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children’s views on the topic, voiced by parents/caregivers. Conclusions Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.

Introduction Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being. Methods This study comprised a systematic review and thematic analysis of qualitative studies with adults and children diagnosed with IgAN. Data sources were identified through an electronic database search of journal articles (MEDLINE, Embase, PsycINFO; June 2021), hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from articles. Extracted data were qualitatively analyzed, aided by ATLAS.ti v7. Codes were applied to data; concepts (i.e., symptoms) were identified, named, and refined. A conceptual model was developed by grouping related concepts into domains. Results In total, five sources were identified for analysis: two journal articles, two online anthologies of patient stories, and one patient organization-sponsored “Voice of the Patient” meeting report. Conceptual model symptom domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight gain, sleep problems, urinary problems, and gastrointestinal problems. Impact domains included emotional/psychological well-being, physical functioning/activities of daily living, social functioning, work/school, and relationships. Conclusions Secondary analysis of published qualitative literature permitted development of a novel conceptual model depicting the patient experience of IgAN; however, its depth is limited by a lack of available literature. Further qualitative research is recommended to refine and/or confirm the concepts and domains, determine any relationships between them, and explore the outcomes that are most meaningful to patients. The refined model will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future IgAN clinical trials.

Introduction: Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease and can progress to end stage kidney disease (ESKD). An overview of symptoms and impacts of the disease experienced will help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in FSGS clinical trials. This study aimed to develop a conceptual model (CM) of the adult and pediatric patient experience of FSGS including disease signs/symptoms, treatment side-effects, and impact on functioning and wellbeing. Methods: This study comprised a systematic review and thematic analysis of qualitative studies with adults and pediatric patients diagnosed with FSGS. Data sources were identified through an electronic database search of journal articles (Medline, Embase, PsycINFO; June 2021) and hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from the articles. Extracted data were qualitatively analyzed aided by ATLAS.ti v7. Codes were applied to data and concepts (symptoms/impacts) were identified, named, and refined. A CM was developed by grouping related concepts into domains. Results: In total, 12 sources were identified for analysis: 6 journal articles and 6 series of patient testimonials. Salient sign/symptom/side-effect domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight changes, skin problems, respiratory problems, and sleep problems. Salient impact domains included emotional/psychological wellbeing, physical functioning/activities of daily living, social functioning, and work/school. Conclusion: Secondary analysis of published qualitative literature permitted development of a CM describing the adult and pediatric experience of FSGS. Concept elicitation interviews are recommended to refine the CM, confirm the salient/most bothersome concepts, and confirm the extent of impact on daily life. The refined CM will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future FSGS clinical trials.

Purpose Traditionally, appropriate anchors are used to investigate the amount of change on a clinician-reported outcome assessment that is meaningful to individual patients. However, novel qualitative methods involving input from disease state experts together with patients may better inform the individual improvement threshold for demonstrating the clinical benefit of new treatments. This study aimed to establish a clinically meaningful threshold for treatment success for the clinician-reported Severity of Alopecia Tool (SALT) score for patients with alopecia areata (AA). Methods A purposive sample of 10 dermatologists expert in AA and 30 adult and adolescent patients with AA and a history of ≥ 50% scalp hair loss were recruited. Semi-structured interview questions explored the outcome that represented treatment success to clinicians and patients. Findings were analyzed using thematic methods to identify treatment success thresholds. Results Both informant groups confirmed scalp hair amount as the outcome of priority. Most expert clinicians considered a static threshold of 80% (n = 5) or 75% (n = 3) of the scalp hair as a treatment success. Most patient responses ranged from 70 to 90% (median: 80% of the scalp hair). Subsequently, queried patients confirmed that achieving SALT score ≤ 20 with treatment would be a success, as reflected in the Alopecia Areata Investigator Global Assessment (AA-IGA™). The novel qualitative processes used to inform this meaningful threshold reflects a clinician-then-patient process for: (a) confirmation of the patient outcome of priority; and (b) clinician input on a preliminary treatment success level for independent understanding among patients. Conclusion This qualitative investigation of expert clinicians-then-patients with AA confirmed that achieving an amount of 80% or more scalp hair (SALT score ≤ 20) was an appropriate individual treatment success threshold indicating clinically meaningful improvement for patients with ≥ 50% scalp hair loss. A qualitative investigation of a quantifiable treatment success threshold is possible through a well-designed interview process with expert clinicians and the appropriate patient population.