Perceptions and Acceptance of a Prophylactic Vaccine for Human Immunodeficiency Virus (HIV): A Qualitative Study.

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.

A conceptual model for chronic hepatitis B and content validity of the Hepatitis B Quality of Life (HBQOL) instrument.

BACKGROUND: There is increased emphasis on incorporating patient perspectives and patient-relevant endpoints in drug development. We developed a conceptual model of the impact of chronic hepatitis B (CHB) on patients' lives and evaluated the content validity of the Hepatitis B Quality of Life (HBQOL) instrument, a patient-reported outcome tool for use in clinical studies, as a patient-relevant endpoint to measure health-related quality of life in patients with CHB. METHODS: A literature review of qualitative studies of patient experience with CHB and concept elicitation telephone interviews with patients with CHB in the United Kingdom were used to develop a conceptual model of the experience and impact of living with CHB. The content validity of the HBQOL was evaluated using cognitive debriefing techniques. RESULTS: The qualitative literature review (N = 43 publications) showed that patients with CHB experience emotional/psychological impacts. During concept elicitation interviews (N = 24), fatigue was the most commonly reported symptom, and most participants were worried/anxious about virus transmission and disease progression/death. A conceptual model of patients' experiences with CHB was developed. The conceptual relevance and comprehensibility of the HBQOL were supported, though limitations, including the lack of a self-stigma item and recall period, were noted for future improvement. CONCLUSIONS: The conceptual model shows that patients with CHB experience emotional/psychological impacts that affect their lifestyles, relationships, and work/schooling. The cognitive debriefing interviews support the content validity of the HBQOL as a conceptually relevant patient-reported outcome measure of health-related quality of life.

Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

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.

Experience and impact of stigma in people with chronic hepatitis B: a qualitative study in Asia, Europe, and the United States.

BACKGROUND: People with chronic hepatitis B (CHB) commonly experience social and self-stigma. This study sought to understand the impacts of CHB-related stigma and a functional cure on stigma. METHODS: Adults with CHB with a wide range of age and education were recruited from 5 countries and participated in 90-minute qualitative, semi-structured interviews to explore concepts related to CHB-associated stigma and its impact. Participants answered open-ended concept-elicitation questions regarding their experience of social and self-stigma, and the potential impact of reduced CHB-related stigma. RESULTS: Sixty-three participants aged 25 to 71 years (15 from the United States and 12 each from China, Germany, Italy, and Japan) reported emotional, lifestyle, and social impacts of living with CHB, including prejudice, marginalization, and negative relationship and work experiences. Self-stigma led to low self-esteem, concealment of CHB status, and social withdrawal. Most participants stated a functional cure for hepatitis B would reduce self-stigma. CONCLUSIONS: CHB-related social and self-stigma are widely prevalent and affect many aspects of life. A functional cure for hepatitis B may reduce social and self-stigma and substantially improve the health-related quality of life of people with CHB. Incorporating stigma into guidelines along with infectivity considerations may broaden the patient groups who should receive treatment.

Development of a Conceptual Model for the Patient Experience of Focal Segmental Glomerulosclerosis (FSGS): A Qualitative Targeted Literature Review.

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.

Using qualitative methods to establish the clinically meaningful threshold for treatment success in alopecia areata.

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.

A Qualitative Study to Develop and Evaluate the Content Validity of the Vitiligo Patient Priority Outcome (ViPPO) Measures.

INTRODUCTION: Vitiligo can be associated with a psychological burden, stigmatization and impaired quality of life. Tools to assess the impact of vitiligo exist; however, none were developed in line with the FDA's patient-reported outcome (PRO) Guidance for Industry. This study aimed to explore the content validity of two newly developed PRO measures to assess the impact of facial and total body vitiligo on how patients feel and function. METHODS: Draft PRO measures were developed from existing literature and input from PRO experts, a patient advocate and a clinical expert. Qualitative interviews were conducted with US participants living with vitiligo and international dermatologists with vitiligo expertise. Concept elicitation methodology explored the relevance of concepts in the draft PRO, while cognitive debriefing assessed conceptual relevance and understanding/interpretation. Items were iteratively amended/added throughout the interview study. RESULTS: The 60 participants included adults (n = 48, 63% female, 18-62 years old) and adolescents (n = 12, 67% female, 12-17 years old) with Fitzpatrick Skin Types I-VI. Expert dermatologists from the US (n = 8), EU (n = 4), India (n = 1) and Egypt (n = 1) participated. Concept elicitation was utilized to confirm the signs/symptoms of vitiligo and the associated impact on emotional/psychological wellbeing, social functioning, daily life and work/school. Conceptual saturation was achieved. Most participants reported impacts on their emotional/psychological wellbeing (n = 57, 95%), e.g. feeling self-conscious (n = 35, 58%). Participants reported impacts on social functioning (n = 53, 88%), e.g. vitiligo being noticed by others (n = 42, 70%). There was general consensus between participants and expert dermatologists. Cognitive debriefing confirmed that the items were well understood. Most items were conceptually relevant; feeling self-conscious and feeling frustrated were highly endorsed. Items were removed based on low conceptual relevance (feeling abandoned, skin roughness) and expected redundancy (four items), resulting in two measures with three proposed domain scores: Emotional/Psychological Wellbeing; Social Functioning; and Physical Sensation. No comprehension concerns were observed in relation to the 7-day recall period or the item response scale/options. Eight dermatologists reviewed the PRO measures, confirming comprehensiveness and relevance. CONCLUSION: The draft Vitiligo Patient Priority Outcomes (ViPPO) measures evaluate the impact of facial (ViPPO-F) and total body (ViPPO-T) vitiligo on emotional/psychological and social functioning. The ViPPO measures are well understood, comprehensive and content valid for adults and adolescents with vitiligo.

Meaningful Changes in What Matters to Individuals with Vitiligo: Content Validity and Meaningful Change Thresholds of the Vitiligo Area Scoring Index (VASI).

INTRODUCTION: This study explored patients' and dermatologists' priority outcomes for treatment to address, clinical outcome assessments (COA) for use in vitiligo clinical trials, and perceptions of within-patient meaningful change in facial and total body vitiligo. METHODS: Semistructured, individual, qualitative interviews were conducted with patients living with non-segmental vitiligo in the USA and with expert dermatologists in vitiligo. Concept elicitation discussions included open-ended questions to identify patient priority outcomes. Vitiligo COAs were reviewed by dermatologists. Tasks were completed by patients to explore their perceptions of meaningful changes in vitiligo outcomes; dermatologists' opinions were elicited. Data were analyzed using thematic methods; meaningful change tasks were descriptively summarized. RESULTS: Individuals with vitiligo (N = 60) included adults (n = 48, 63% female) and adolescents (n = 12, 67% female). All Fitzpatrick Skin Types were represented. Eight (13%) were first- or second-generation immigrants to the USA. Expert dermatologists (N = 14) participated from the USA (n = 8), EU (n = 4), India (n = 1), and Egypt (n = 1). All individuals with vitiligo reported experiencing skin depigmentation; an observable clinical sign of vitiligo. Most confirmed that lesion surface area (n = 59/60, 98%) and level of pigmentation (n = 53/60, 88%) were important to include in disease assessments. Following an explanation, participants (n = 49/60, 82%) felt that the Facial Vitiligo Area Scoring Index (F-VASI) measurement generally made sense and understood that doctors would use it to assess facial vitiligo. Most participants felt that a 75% (n = 47/59, 80%) or 9 0% improvement in their facial vitiligo would be indicative of treatment success (n = 55/59, 93%). In the context of evaluating a systemic oral treatment for vitiligo, dermatologists perceived a 75% improvement on the F-VASI as successful (n = 9/14, 64%). Regarding the Total VASI (T-VASI) score, n = 30 participants considered 33% improvement as treatment success; an additional n = 10 endorsed 50% improvement and a further n = 5 endorsed 75% improvement. Clinicians most frequently identified 50% (n = 6/14, 43%) or 75% (n = 4/14, 29%) improvement in T-VASI as successful. CONCLUSION: Repigmentation is a priority outcome for patients. The VASI was considered an appropriate tool to assess the extent of vitiligo. A minimum 75% improvement from baseline in the F-VASI and minimum 50% improvement from baseline in the T-VASI were identified as within-patient clinically meaningful thresholds.

Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

BACKGROUND: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Cognitive debriefing methodology explored relevance and understanding of selected COAs. RESULTS: Interviews (N = 36) were conducted with caregivers of children age 0-2 years (n = 8) and 3-7 years (n = 7) and child/caregiver dyads with children age 8-11 years (n = 15) and 12-17 years (n = 6). Children/caregivers identified pain, short stature, impacts on physical functioning, and impacts on well-being (e.g. negative attention/comments) as key bothersome aspects of achondroplasia. Caregivers considered an increase in height (n = 9/14, 64%) and an improvement in limb proportion (n = 11/14, 71%) as successful treatment outcomes. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed. CHAQ items evaluating activities, reaching, and hygiene were most relevant. QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant. The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17. Some children aged 8-11 had difficulty reading, understanding, or required caregiver input. Feedback informed minor amendments to the CHAQ and the addition of a 7-day recall period to the QoLISSY-Brief. These amendments were subsequently reviewed and confirmed in N = 12 interviews with caregivers of children age 0-11 (n = 9) and adolescents age 12-17 (n = 3). CONCLUSIONS: Achondroplasia impacts physical functioning and emotional/social well-being. An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach. The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.

A qualitative interview study to explore adolescents' experience of alopecia areata and the content validity of sign/symptom patient-reported outcome measures.

BACKGROUND: The content validity (appropriateness and acceptability) of patient-reported outcome (PRO) measures for scalp hair loss, eyebrow loss, eyelash loss, nail damage and eye irritation has been demonstrated in adults with alopecia areata (AA) but not adolescents. OBJECTIVES: To explore the content validity of the suite of AA PRO measures and accompanying photoguides in an adolescent sample. METHODS: Semi-structured, 90-min, combined concept elicitation and cognitive interviews were conducted face-to-face with adolescents who experienced ≥ 50% AA-related scalp hair loss. Transcripts underwent thematic and framework analysis. RESULTS: Eleven adolescents (aged 12-17 years, 55% female, 45% nonwhite) diagnosed with AA for 5·9 years (mean) participated. Participants had 69·6% scalp hair (mean) and current eyebrow (82%) and/or eyelash loss (82%) and/or nail involvement (36%). Adolescents reported scalp, eyebrow and eyelash hair loss as their top three most bothersome signs/symptoms. Despite mostly accepting their AA, impacts related to visible areas of hair loss were prominent. Participants demonstrated good understanding and appropriate use of the PRO measures, and advocated including hair loss percentages alongside descriptive categories in the Scalp Hair Assessment PRO™. Results confirmed treatment success thresholds established with adults: achievement of ≤ 20% scalp hair loss, no/minimal eyebrow and eyelash loss, no/a little nail damage and eye irritation (PRO measure categories 0 or 1). CONCLUSIONS: The Scalp Hair Assessment PRO™, PRO Measure for Eyebrows™, PRO Measure for Eyelashes™, PRO Measure for Nail Appearance™ and PRO Measure for Eye Irritation™ and accompanying photoguides are fit-for-purpose self-reported measures of AA signs/symptoms that are impactful to adolescents with AA.

Dermatologist and Patient Perceptions of Treatment Success in Alopecia Areata and Evaluation of Clinical Outcome Assessments in Japan.

INTRODUCTION: The content validity and treatment success thresholds of clinical outcome assessments (COAs) for alopecia areata (AA)-including the Alopecia Areata-Investigator Global Assessment™ (AA-IGA™), Scalp Hair Assessment Patient-Reported Outcome™ (PRO), and clinician-reported outcome (ClinRO) and PRO measures for eyebrows, eyelashes, eye irritation, and nails-were established in interviews with dermatologists and patients in North America. This study aimed to confirm the content validity and treatment success thresholds of these measures with clinicians and patients in Japan. METHODS: Qualitative interviews were conducted in Japan with dermatologists with AA expertise and adults with AA who experienced ≥ 50% scalp hair loss. Interviews included concept elicitation and cognitive interview questions. Data were analyzed using thematic and framework techniques. RESULTS: Seven dermatologists and 15 patients participated. Scalp hair loss was the most important sign/symptom of AA and the greatest treatment priority. Dermatologists and patients understood the AA-IGA™, Scalp Hair Assessment PRO™, and other COAs, and found these measures to be appropriate, relevant, and clinically meaningful. Dermatologists and patients confirmed that achieving ≤ 20% scalp hair loss (AA-IGA™/Scalp Hair Assessment PRO™ categories 0 or 1) indicated treatment success for patients with ≥ 50% scalp hair loss. Categories 0 or 1 on the other COAs represented treatment success. CONCLUSION: This study confirmed the content validity and treatment success thresholds of the AA-IGA™, Scalp Hair Assessment PRO™, and other ClinRO and PRO measures for AA in Japan. These findings were aligned with interview results in North America and support the use of these measures in AA treatment studies.

About 2% of people in the world have alopecia areata, which causes them to lose hair on their scalp, face, and body. We interviewed 15 Japanese adults who had lost at least half of the hair on their scalp and seven dermatologists who treated alopecia areata. The dermatologists felt that scalp hair loss was more important to treat than eyebrow and eyelash hair loss. Patients were most bothered about losing their scalp hair and reported feeling anxious or worried about what other people might think about it. Patients and dermatologists were also shown several questionnaires and thought the questionnaires were appropriate to measure the most important symptoms of alopecia areata. Patients considered that a treatment worked well if it gave them at least 80% of their scalp hair; dermatologists also wanted the treatment to give patients at least 80% scalp hair. These interviews agree with what has previously been found in interviews with patients and dermatologists in North America.

Patients' and clinicians' perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS).

BACKGROUND: The Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS) are patient-reported outcome measures developed to evaluate efficacy in clinical trials and clinical practice. The ESD is a daily electronic diary assessing symptom severity; the EIS is a weekly electronic diary assessing symptom impact. This study explored the importance of symptoms (ESD items) and impacts (EIS domains), perspectives on scoring algorithms, and clinically important difference (CID) thresholds to inform clinical trial score interpretation. METHODS: Endometriosis patients in Germany (n = 8) and the US (n = 17), and expert clinicians (n = 4) in Germany, the US, Spain, and Finland participated in semi-structured qualitative interviews comprising structured tasks. Interview transcripts were analyzed using thematic analysis techniques. RESULTS: Quality and severity of endometriosis-associated pelvic pain varied considerably among patients; some experienced pelvic pain daily, others during menstrual bleeding (dysmenorrhea) only. Patients and clinicians ranked "worst pelvic pain" as the most meaningful pain concept assessed by the ESD, followed by constant and short-term pelvic pain. Preferences for summarizing daily pain scores over the 28-day menstrual cycle depended on individuals' experience of pain: patients experiencing pain daily preferred scores summarizing data for all 28 days; patients primarily experiencing pain during selected days, and their treating clinicians preferred scores based on the most severe pain days. Initial CID exploration for the "worst pelvic pain" 0-10 numerical rating scale (0-10 NRS) revealed that, for most patients, a 2- or 3-point reduction was considered meaningful, depending on baseline severity. Patients and clinicians ranked "emotional well-being" and "limitations in physical activities" as the most important EIS domains. CONCLUSIONS: This study informs the use of the ESD and EIS as clinically relevant measures of endometriosis symptoms and their impact. Findings from the ESD highlight the importance of individual-patient assessment of pain experience and identify "worst pelvic pain" as the most meaningful symptom assessed. Aggregating scores over the 28-day menstrual cycle may inform meaningful endpoints for clinical trials. Diverse EIS concepts (e.g. impact on emotional well-being and physical activities) are meaningful to patients and clinicians, emphasizing the importance of evaluating the impact on both to comprehensively assess treatment efficacy and decisions. TRIAL REGISTRATION: Not applicable. Qualitative, non-interventional study; registration not required.

The Role of Patients in Alopecia Areata Endpoint Development: Understanding Physical Signs and Symptoms.

Meaningful patient input to understand disease experience and patient expectations for improvement with treatment is essential for the selection and development of outcome measures for alopecia areata (AA) clinical trials. This study explored the physical signs and symptoms of AA through 30 semistructured interviews with adult (n = 25) and adolescent (n = 5) patients experienced with severe or very severe AA. Scalp hair loss was overwhelmingly the most important sign and symptom of AA. Nearly all patients (90%) considered scalp hair loss in their top three most bothersome physical signs and symptoms of AA, with 77% (n = 23) naming scalp hair loss as the most bothersome symptom. Other identified signs and symptoms in the top three most bothersome included eyebrow, eyelash, nose, body, and facial hair loss, as well as eye irritation and nail damage and/or appearance. Eyebrow (16%, n = 4), eyelash (4%, n = 1), nasal (4%, n = 1), and body (4%, n = 1) hair loss were identified by seven adult patients as the most bothersome signs and symptoms of AA. Conceptual saturation confirmed that a comprehensive understanding of this patient population's physical AA-related signs and symptoms was obtained. These findings indicate that the primary objective for new AA treatments for this patient population should be meaningful improvement in scalp hair growth to address the most troubling unmet need.

"'You lose your hair, what's the big deal?' I was so embarrassed, I was so self-conscious, I was so depressed:" a qualitative interview study to understand the psychosocial burden of alopecia areata.

BACKGROUND: Alopecia areata (AA) is characterized by hair loss that can affect the scalp and body. This study describes the psychosocial burden of AA. METHODS: Participants diagnosed with AA who had experienced ≥50% scalp hair loss according to the Severity of Alopecia Tool (SALT) were identified by clinicians. A semi-structured interview guide, developed with expert clinician input, included open-ended questions to explore patients' experiences of living with AA. Data were thematically analyzed to identify concepts and relationships. RESULTS: Participants (n = 45, 58% female, mean age 33.3 years [range 15-72], mean SALT 67.2 [range 0-100]) described the AA diagnosis as "devastating". Both males and females reported emotional and psychological impacts of AA including feeling sad/depressed (n = 21), embarrassed/ashamed (n = 10) and angry/frustrated (n = 3). Patients felt helpless (n = 5) due to the unpredictability of disease recurrence, and anxious (n = 19) about judgement from others. Many patients avoided social situations (n = 18), which impaired relationships and increased isolation. Coping strategies included concealment of hair loss through wigs or make-up, although fear of the displacement of these coverings also caused anxiety and the avoidance of activities that could result in scalp exposure (n = 22). Some patients became more accepting of AA over time, which lessened the emotional impact, though efficacious treatment was still desired. A conceptual framework was developed, and a conceptual model was created to depict the relationship between the physical signs/symptoms and the associated psychosocial effects of AA. CONCLUSION: AA impairs patients' emotional and psychological wellbeing, relationships and lifestyles. Greater disease awareness and effective treatments are needed.

Development of Clinician-Reported Outcome (ClinRO) and Patient-Reported Outcome (PRO) Measures for Eyebrow, Eyelash and Nail Assessment in Alopecia Areata.

BACKGROUND: Eyebrow and eyelash hair loss and nail damage-in addition to scalp hair loss-are important signs/symptoms of alopecia areata (AA) to patients and deserve assessment in AA clinical trials. OBJECTIVES: Our objective was to develop clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures and accompanying photoguides to aid in the assessment of AA-related eyebrow, eyelash and nail signs/symptoms. METHODS: Iterative rounds of qualitative, semi-structured interviews were conducted with US expert dermatologists and North American patients with AA. Patients with eyebrow, eyelash and nail involvement were purposefully sampled. Interview transcripts were qualitatively analyzed. RESULTS: Dermatologists (n = 10) described eyebrow and eyelash loss as concerning for affected patients and, along with nail appearance, as deserving assessment. Dermatologist data informed the development of single item, 4-point Likert-type ClinRO and PRO measures of current eyebrow loss, eyelash loss and nail appearance and a PRO measure of eye irritation. Patients (n = 45, age 15-72 years) confirmed the importance and relevance of these signs/symptoms. Interim revision resulted in measures that were understood by and relevant to patients. Dermatologists (n = 5) and patients (n = 10, age 21-54 years) participated in the development of the eyebrow, eyelash and nail photoguides and confirmed that they included photos that appropriately represented different severity levels and were helpful to derive and standardize ratings across raters. CONCLUSIONS: The ClinRO and PRO measures for eyebrow, eyelash and nail appearance, with their accompanying photoguides and the PRO Measure for Eye Irritation provide clear and meaningful assessments of outcomes important to patients with AA.

Patient's Perspective on Disease Burden, Remission Definition, and Symptoms Associated With Treatment Seeking: A Qualitative Study in Adult and Adolescent Patients With Crohn's Disease.

Background: Disease burden, a definition of remission, and symptoms that drive treatment seeking were explored in a Crohn's disease (CD) population. Methods: A qualitative semistructured interview guide was developed, informed by published literature. Clinicians identified adolescents and adult patients with CD. Face-to-face interviews were audio-recorded and transcribed. Two rounds of interviews were conducted with patients. Transcripts were analyzed using thematic methods facilitated by ATLAS.ti. Results: Twenty-four patients participated in the first round of interviews (n = 16 adults, mean age 50.3 years; n = 8 adolescents, mean age 15.6 years). Abdominal pain (n = 24), urgent bowel movements (n = 24), diarrhea (n = 23), and frequent bowel movements (n = 21) were the most frequently reported symptoms. CD affected patients' physical functioning, daily activities, emotional wellbeing, social functioning, work/education, and relationships. No major difference in disease burden was observed between adolescents and adults. Twenty-three patients (96%) reported they would seek or had sought medical treatment for at least one symptom including abdominal pain (n = 19), diarrhea (n = 12), and blood in stools/rectal bleeding (n = 9). On a 0-10 scale (0 = no symptom and 10 = symptom at its worst possible), most patients (87%, 20/23) answered they would seek/had sought treatment when the symptom's severity was at least 7. In the second round of interviews (n = 6 adults, mean age 51.5 years), 5/6 patients described that they did not require a complete absence of abdominal pain or loose/watery stools to consider their CD to be in remission. Conclusions: CD is associated with substantial disease burden. Worsening of some symptoms drives treatment seeking. To some patients, remission is not defined as a complete absence of symptoms.

Exploring the patient experience of locally advanced or metastatic pancreatic cancer to inform patient-reported outcomes assessment.

PURPOSE: Pancreatic cancer and its treatments impact patients' symptoms, functioning, and quality of life. Content-valid patient-reported outcome (PRO) instruments are required to assess outcomes in clinical trials. This study aimed to: (a) conceptualise the patient experience of pancreatic cancer; (b) identify relevant PRO instruments; (c) review the content validity of mapped instruments to guide PRO measurement in clinical trials. METHODS: Qualitative literature and interviews with clinicians and patients were analysed thematically to develop a conceptual model of patient experience. PRO instruments were reviewed against the conceptual model to identify gaps in measurement. Cognitive debriefing explored PRO conceptual relevance and patients' understanding. RESULTS: Patients in the USA (N = 24, aged 35-84) and six clinicians (from US and Europe) were interviewed. Pre-diagnosis, pain was the most frequently reported symptom (N = 21). Treatments included surgery, radiation, chemotherapy, and immunotherapy. Surgery was associated with acute pain and gastrointestinal symptoms. Chemotherapy/chemoradiation side effects were cyclical and included fatigue/tiredness (N = 21), appetite loss (N = 15), bowel problems (N = 15), and nausea/vomiting (N = 15). Patients' functioning and well-being were impaired. The literature review identified 49 PRO measures; the EORTC QLQ-C30/PAN26 were used most frequently and mapped with interview concepts. Patients found the EORTC QLQ-C30/PAN26 to be understandable and relevant; neuropathic side effects were suggested additions. CONCLUSIONS: This is the first study to develop a conceptual model of patients' experience of metastatic/recurrent pancreatic cancer and explore the content validity of the EORTC QLQ-C30/PAN26 following therapeutic advances. The EORTC QLQ-C30/PAN26 appears conceptually relevant; additional items to assess neuropathic side effects are recommended. A recall period should be stated throughout to standardise responses.

Psychometric Validation of the Hepatitis C Symptom and Impact Questionnaire (HCV-SIQv4) in a Diverse Sample of Adults with Chronic Hepatitis C Virus Infection Treated with an Interferon-free Simeprevir-containing Regimen.

BACKGROUND: Hepatitis C virus (HCV) infection and its treatments are associated with significant symptoms, side effects and impact on patients functioning. The Hepatitis C Symptom and Impact Questionnaire version 4 (HCV-SIQv4) was developed according to FDA Patient Reported Outcomes (PRO) Guidance, for evaluating chronic HCV infection and its treatment. OBJECTIVES: This study evaluated the psychometric properties and clinically important change (CIC) thresholds of the measure. METHODS: PRO data were pooled from three Phase IIb and III trials evaluating interferon-free simeprevir-containing regimens for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness and CIC thresholds were assessed incorporating knowledge of the appropriate measurement model. RESULTS: Data from 437 patients were analyzed. Stage of liver disease was associated with symptom severity and functioning at baseline. Reliability was acceptable (test-retest ICC ≥0.7) for most scores except the Gastrointestinal and Integumentary domains. Convergent validity was observed between HCV-SIQv4 scores and concurrent measures of conceptual similarity. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue and health limitations. Patients who achieved SVR12 had better outcomes than those failing to. HCV-SIQv4 symptom and domain scores were responsive to changes in health state (effect sizes ≥0.5). Exploratory thresholds for change in scores indicating a clinically important improvement and worsening were HCV-SIQv4 Overall Body System Score (BSS), 8 and 8; Constitutional BSS, 10 and 10; Gastrointestinal BSS, 5 and 5; Psychiatric BSS, 8 and 8; Neurocognitive BSS, 8 and 8; and Integumentary BSS, 5 and 5. CONCLUSIONS: The HCV-SIQv4 offers reliable, responsive assessments within HCV clinical development. CIC thresholds are now available to aid score interpretation.

Healthcare Resource Utilization and Costs Associated with Ketosis Events in Pediatric and Adult Patients with Type 1 Diabetes Mellitus in the UK.

INTRODUCTION: Ketosis is a metabolic state associated with insulin deficiency. Untreated, it develops into diabetic ketoacidosis, a significant contributor to mortality and morbidity in people with type 1 diabetes mellitus (T1DM). Little is understood about how patients utilize healthcare resources during ketosis events. This study aimed to identify and quantify healthcare resource utilization and provide estimates of associated costs of ketosis events in T1DM, treated unaided or with healthcare professional (HCP) assistance in the UK. METHODS: Qualitative interviews with adult patients, pediatric carers, and HCPs identified resources used by patients/carers during ketosis events. An online quantitative survey was then used to quantify patients/carers resource use during their/their child's most recent ketosis event, and HCPs estimated patient resource uptake to corroborate the findings. Associated costs estimated from UK data sources were applied to the survey results to calculate the cost of ketosis events in adults and children. RESULTS: Quantitative survey responses from 93 adults, 76 carers, and 52 HCPs were analyzed. Patients and carers monitored ketosis during and following the event with ketone strips and additional glucose strips, and administered treatment comprising insulin and pump set changes where appropriate. Additionally, patients/carers accessed phone services and many received follow-up medical appointments. In total, 70% (n = 65) of adult and 66% (n = 50) of pediatric ketosis events were managed at home, for which resource use costs per event were £23.87 and £38.00 respectively. Remaining events were treated in NHS facilities costing £217.57 per adult and £352.92 per child. Weighted averages identified that ketosis events cost £81.98 per adult and £142.97 per child. Indirect costs from work productivity loss increase these figures to £225.11 per adult and £256.88 per child. CONCLUSIONS: Healthcare resource use for ketosis events is high in adults and children with T1DM and imposes an underappreciated economic burden for the NHS. FUNDING: Novo Nordisk A/S.

A review of patient-reported outcome measures to assess female infertility-related quality of life.

BACKGROUND: Infertility has a negative impact on quality of life (QoL) and well-being of affected individuals and couples. A variety of patient-reported outcome (PRO) measures to assess infertility-related QoL are available; however, there is a concern regarding potential issues with their development methodology, validation and use. This review aimed to i) identify PRO measures used in infertility interventional studies ii) assess validation evidence to identify a reliable, valid PRO measure to assess changes in QoL or treatment satisfaction in clinical studies with female patients following treatment with novel therapies iii) identify potential gaps in evidence for validity. METHODS: A structured literature search of Medline, Embase, and the Cochrane Library (accessed in September 2015) was conducted using pre-defined search terms. The identified publications were reviewed applying eligibility criteria to select interventional female infertility studies using PROs. Infertility-specific PRO measures assessing QoL, treatment satisfaction or psychiatric health, and included in studies by ≥2 research groups were selected and critically reviewed in light of scientific and regulatory guidance (e.g. FDA PRO Guidance for Industry) for evidence of content validity, psychometric strength, and patient acceptability. RESULTS: The literature search and hand-searching yielded 122 publications; 78 unique PRO measures assessing QoL, treatment satisfaction or psychiatric health were identified. Five PRO measures met the selection criteria for detailed review: Fertility Quality of Life (FertiQoL); Fertility Problem Inventory (FPI); Fertility Problem Stress (FPS); Infertility Questionnaire (IFQ); Illness Cognitions Questionnaire adapted for Infertility (ICQ-I). None of the PRO measures met all validation criteria. The FertiQoL was the most widely used infertility-specific PRO measure to assess QoL in interventional studies, with reasonable evidence for adequate content validity, psychometric strength, and linguistic validation. However, gaps in evidence remain including test-retest reliability and thresholds for interpreting clinically important changes. While the FPI demonstrated reasonable evidence for content and psychometric validity, its utility as an outcome measure is limited by a lack of recall period. CONCLUSION: The FertiQoL and the FPI are potentially useful measures of infertility-related QoL in interventional studies. Further research is recommended to address gaps in evidence and confirm both PRO measures as reliable assessments of patient outcomes.