Lyme disease (LD) is the most common tick-borne illness in the USA, with an estimated 476,000 cases diagnosed and treated annually. Common signs, symptoms, and manifestations of LD are well described; however, there is limited qualitative understanding of the signs and symptoms patients experience during their illness and the associated impacts patients endure along the way. Thus, we aimed to explore the patient journey and experience with LD, including patient-reported signs and symptoms and impacts to health-related quality of life (HRQOL). No a priori hypotheses were evaluated. In-depth, one-on-one, semi-structured interviews were conducted with US adults aged ≥ 18 years who had physician-diagnosed LD in 2023 to explore their experience with LD diagnosis, management, and treatment. The EQ-5D (a standardised HRQOL measure) was administered, and a patient journey map was developed. Interview transcripts were analysed via inductive and deductive coding, using an experiential, realist approach. Twenty-five participants with LD were interviewed (female, 13/25, 52

Introduction & Objective: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome. Individuals living with HFpEF and obesity display a distinct phenotype that places considerable burden on their health-related quality of life. This study explored signs, symptoms, and impacts most relevant to individuals living with HFpEF and obesity. Clinician interviews provided a clinical perspective on the patient experience. Methods: Qualitative interviews were conducted virtually with adults in the US diagnosed with HFpEF and obesity (body mass index ≥30.0 kg/m2). Clinicians in the US, China, and Germany with ≥3 years of experience treating HFpEF were also interviewed. Patient interviews were conducted until conceptual saturation was achieved. Content analysis was conducted using ATLAS.ti v9.0 software. A conceptual model (CM) of the lived experience of HFpEF and obesity based on patient and clinician feedback was developed. Results: Twenty-two patients and 6 clinicians participated in the interviews. The CM demonstrated that living with HFpEF impacts many facets of life, with participants and clinicians reporting impacts on their (or their patients’) physical functioning (e.g., walking), activities of daily living (e.g., household chores) and work. Participants also reported impacts on their emotional well-being (e.g., feeling anxious or worried), social lives, relationships, and sleep. Shortness of breath and fatigue were spontaneously noted as salient and bothersome symptoms by most participants with edema noted by most on probing; this was further corroborated by clinicians who also considered these symptoms as the most bothersome symptoms of HFpEF. Conclusion: This study highlighted the substantial burden of living with HFpEF and obesity. The resultant conceptual model highlights the key concepts that should be considered in patient-focused drug development. Disclosure C. Kanu: None. T. Al-Zubeidi: Consultant; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Edgewise Therapeutics, Alimentiv. Employee; Clarivate Analytics. Consultant; Pfizer Inc. S. Shinde: None. G. Al-Jassar: None. J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Miller: Employee; Clarivate. Other Relationship; Clarivate. C. Marshall: None. C. Carmichael: Employee; Clarivate. Stock/Shareholder; Clarivate. Other Relationship; Clarivate.

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 : 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 practical recommendations for future studies. Methods : We reviewed four qualitative studies designed to inform the development or validation of ClinROs. Contexts were varied, including prion disease, alopecia areata, dermatomyositis, and vitiligo. 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 practical recommendations for incorporating patient/caregiver input during ClinRO development and validation. When gathering patient/caregiver input, researchers should: 1) frame the purpose; 2) use multimodal supports; 3) simplify scoring for the task; 4) map language; 5) elicit thresholds and 6) align endpoints. 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 can provide 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. Practical recommendations are provided for incorporating patient/caregiver input into ClinRO evidence generation to inform patient-focused clinical trial measurement strategies.

Background:Digital health technologies (DHTs) offer passive, objective, and continuous monitoring of difficult-to-report mobility-related behaviors like physical activity (PA) and functional mobility (FM), which are important concepts of interest in obesity-related clinical studies. This study was conducted to identify which aspects of FM/PA are meaningful to people living with obesity or overweight and establish how those concepts can be measured by passive monitoring using DHTs. Methods:Qualitative concept elicitation interviews were conducted among 4 groups of adults (≥18 years) with obesity (body mass index [BMI] ≥30 kg/m2) and no obesity-related complications, overweight (BMI ≥27 kg/m2) with type 2 diabetes, overweight with obstructive sleep apnea, and overweight with lower-limb osteoarthritis. Two rounds of interviews were conducted to first identify the most important concepts of interest relating to FM/PA and then determine what level of change in FM and PA would be considered meaningful and important in the context of obesity treatment. Results:A total of 48 participants were recruited for Round 1 (n = 24) and Round 2 (n = 24). The most frequently reported concepts of interest identified for FM and PA were walking on a flat surface, moderate-to-vigorous physical activity (MVPA), climbing stairs, walking uphill, and standing. All four most frequently reported concepts of FM/PA in Round 1 (MVPA, going up stairs, walking, and standing) were also considered relevant and bothersome in Round 2. The majority of the participants confirmed that measuring step count and changes in minutes of MVPA would be meaningful for them with respect to treatment for obesity. Conclusion:People with obesity or overweight reported the ability to perform MVPA, going up stairs, walking, and standing as meaningful FM/PA outcomes. DHTs have the potential to provide relevant information about the functional status of people with obesity and could be more frequently implemented in obesity treatment studies and clinical practice.

Background The prion diseases (PrD) are a group of progressive, fatal, neurodegenerative diseases, for which the Medical Research Council Prion Disease Rating Scale (MRC Scale) can be used to assess patients’ functional deterioration. Findings from previous qualitative interviews with caregivers and clinical experts identified potential ambiguities in the scale that could lead to inconsistent scoring within and/or between raters.Methods A draft User Guide was developed based on findings from a previous qualitative study. The draft included clarifications regarding domain wording, scoring levels, and guidance for response option selection. Five clinical experts with PrD management experience provided written feedback on the draft User Guide, which was incorporated into a revised User Guide. A 90-minute consensus meeting was then held with these experts to confirm the final content to be included in the User Guide.Results The final User Guide was designed to accompany the MRC Scale and assist with rater decisions related to which response option most accurately describes a patient’s health status. Conclusions: The User Guide is expected to be a valuable complement to the MRC Scale, which is poised to rise in use and prominence as global clinical research efforts accelerate to address the significant unmet need of PrD patients.

Dermatomyositis (DM) is a rare systemic autoimmune disease characterized by a distinctive debilitating skin rash and skeletal muscle weakness. It is unclear if existing clinical outcome assessment (COA) measures include the concepts of priority to patients and those necessary to fully capture improvements in the active cutaneous manifestations of DM. This study aimed to develop the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA), a de novo IGA, for use in clinical trials of adult DM. Eight DM clinical experts participated in 60-min qualitative interviews consisting of concept elicitation and cognitive debriefing methodologies. Concept elicitation comprised open-ended questions with follow-up probes to explore clinicians’ experiences of treating patients with DM, the impact of symptoms on patients’ quality of life, and the severity levels of disease characteristics to explore DM progression. Cognitive debriefing required the clinical experts to perform a review of the CDM-IGA, designed to assess the severity of cutaneous disease activity of DM. After the interviews, a consensus meeting with three clinical experts was held to agree on any outstanding issues relating to the CDM-IGA. The CDM-IGA was iteratively developed using the opinions of nine clinical experts. Feedback provided by all clinicians agreed that erythema was the main active cutaneous manifestation of DM and should be the primary characteristic on the CDM-IGA, split by erythema color and extent. To determine cutaneous disease severity, experts suggested adding a metric called secondary changes, which combined erosion/ulceration and lichenification, which could modify the patient’s final score. Three clinical experts suggested that a photo-guide to support assessments of erythema across different skin tones could be beneficial. A novel CDM-IGA was developed for use with adult patients with DM in clinical trials, based on an iterative development process that combined qualitative feedback from clinical experts of DM and importantly adult patients living with DM.

Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments. The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures. Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients’ experiences of DM, including the symptoms and impacts on their daily lives and wellbeing. Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100

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.

Background and objective The chest-related electronic patient reported outcome (ePRO) diary was recently developed to assess chest-related symptoms experienced by pediatric and adolescent populations during upper respiratory tract infections (URTI). The objective of this research was the psychometric evaluation of the chest-related ePRO diary in pediatric, adolescent and adult participants. Methods This non-interventional, psychometric validation study involved participants (N = 195; n = 42 6–8 years; n = 47 9–11 years; n = 55 12–17 years, n = 51 18+ years) completing the chest-related ePRO diary twice daily for 10 days while experiencing an acute URTI. Preliminary item-level performance and dimensionality results, along with consideration of previous qualitative findings, were used to inform item reduction decisions, the structure of the measure and scoring algorithm development. Subsequent analyses on the finalized measure included assessments of reliability (internal consistency and test-retest reliability), construct validity (convergent validity and known groups validity) and ability to detect change. Comparisons of findings were made between the different age groups as part of the analyses to assess the psychometric properties of the chest-related ePRO diary and to characterize potential differences in the symptom experience of children, adolescents, and adults. Results The measure demonstrated strong quality of completion and showed relatively similar trajectories of symptom scores over time within different age subgroups and good item response distribution properties. Exploratory factor analysis supported a one-factor solution in the total population and within age subgroups, and test-retest reliability of the measure was strong (Intra-class correlation: 0.843–0.894 between Visit 1 and Day 1). The measure also demonstrated strong construct validity through high correlations with relevant items on the Child Cold Symptom Questionnaire (CCSQ), strong known groups validity (with statistically significant differences between severity groups) and was responsive to change over time with change groups defined based on change on global items. Conclusion The findings demonstrate that the chest-related ePRO diary provides a valid, reliable, responsive measure of chest congestion symptoms experienced with the common cold in pediatric and adolescent populations, and that only minor differences are present in the disease trajectory when comparing adults to younger participants, supporting the use of the measure in interventional studies.

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. 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. 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. 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.

This study explored perceptions of meaningful weight-loss and the level of change on two patient-reported outcome (PRO) measures, the 36-item Short Form Health Survey® [SF-36v2®] and Impact of Weight on Quality of Life Lite-Clinical Trials© [IWQOL-Lite-CT©], that individuals living with overweight or obesity consider to be meaningful and indicative of treatment success. Thirty-three qualitative interviews were conducted in the US with adults living with overweight or obesity. Concept elicitation explored perceptions of minimally important/meaningful weight-loss using open-ended questions. Cognitive debriefing was used to understand thresholds for meaningful change on both measures. Most participants (n = 23/33) expected a 5% total body weight-loss to yield some benefit in physical functioning, while all participants expected a 10% weight-loss to provide a meaningful and noticeable improvement in their physical functioning. Participants indicated that an item-level 1-point score change on each measure would represent a noticeable improvement in physical functioning and indicate treatment success. Participants expected moderate weight-losses to be noticeable, with ≥ 10% weight-loss yielding the most consistent results. The findings suggested that both measures provide strong opportunity to demonstrate treatment benefit in relation to physical functioning as a small change on the response scale would represent a noticeable improvement in participants’ daily lives.

Abstract Background People with classic congenital adrenal hyperplasia (CAH) often require supraphysiologic doses of glucocorticoids (e.g., hydrocortisone, dexamethasone) to treat cortisol deficiency and excess androgen production. Healthcare providers and patients continually try to balance androgen control with side effects from supraphysiologic glucocorticoids. This study aimed to understand the preferences of adults with classic CAH regarding benefits of a potential new adjunctive medication that may provide better androgen control and allow for lower glucocorticoid doses. Methods Discrete choice experiment (DCE) methodology was used to calculate the relative stated preferences for the additional therapy's hypothetical benefits (attributes). Seven attributes were developed for the DCE after review of relevant data and qualitative literature, interviews with eight adults with classic CAH and input from two endocrinologists. The online DCE survey was piloted via interviews with three adults with classic CAH and a soft launch, which confirmed survey content and functioning. Preference data and subgroup differences were analyzed using conditional logit and scale assessment modelling, respectively. Results US adults with classic CAH (N=118, 75% female, age 19–69) valued avoidance of glucocorticoid-induced weight gain by twice the magnitude of other treatment attributes (all coefficients p<0.001 compared to baseline levels of no avoidance/decrease/improvement): complete avoidance of weight gain from glucocorticoids (1.109); moderate decrease in risk of developing health conditions from long-term glucocorticoids: type 2 diabetes (0.540), osteopenia, osteoporosis, fractures (0.521) and cardiovascular disease (0.502); moderate improvement in: fatigue (0.439), fertility (0.437) and excessive body hair (females only) and acne (0.410). Avoidance of glucocorticoid-induced weight gain remained the most preferred attribute across all subgroup analyses. Avoidance of glucocorticoid-induced weight gain was relatively much more important to females (n=89) than males (n=28) and participants with a body mass index ≥30 (n=70) than <30 (n=48). Improvement in fertility was more important to males than females, was valued by participants aged 18–45 (n=82) but was not a significant preference in participants >45 (n=36) and was relatively more important to participants with fertility problems (n=31) than without (n=87). Improvement in hirsutism and acne was highly valued by participants with excessive hair growth (n=38) but had the lowest preference among those without (n=80). Improvement in fatigue was a significant preference for participants with energy problems (n=73) but was not significant for those without (n=45). Conclusions The strong and consistent preference for avoiding glucocorticoid-induced weight gain suggests that patients with classic CAH would most value a novel adjunctive therapy that helps mitigate glucocorticoid-induced weight gain. In relation to other potential adjunctive therapy benefits, reduced risk of glucocorticoid-driven side effects may be valued more than improvement in fatigue or androgen-driven adverse events (fertility and hirsutism/acne). However, subgroup analyses indicated that individuals’ characteristics impact their treatment preferences and priorities, after avoidance of glucocorticoid-induced weight gain. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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.

Background This article describes qualitative interviews conducted with children (aged 6–11), adolescents (aged 12–17), and adults with the common cold as well as parents/caregivers of the 6–8-year-old children. The aim was to support the refinement and content validity testing of patient-reported outcome (PRO) items assessing chest congestion that could be used as pediatric clinical trial endpoints. Feasibility and acceptability of administering the PRO items electronically on a hand-held touch-screen device were also evaluated. The sample included children aged 6–8 years (n = 14), 9–11 years (n = 13), adolescents aged 12–17 years (n = 12), and adults (n = 10), all of who had current (n = 38) or recent (n = 11) cold. Both concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted with all of these participants, conducted over in two rounds. Ten parents/caregivers of participants aged 6–8 years were also interviewed (separately from their child) regarding how they thought their children would understand the items. The CE interviews explored the qualitative experience of having chest congestion and related symptoms of the common cold. Following their CE interview, participants completed draft items on an electronic patient-reported outcome (ePRO) device twice daily for 2–5 days prior to their CD interview. During the CD interview participants were asked about relevance, understanding and interpretation of the draft PRO items. Qualitative analysis of the interview data and descriptive analyses of the ePRO data were conducted following both rounds of interviews, with modifications to the items implemented following Round 1 and tested in Round 2. Results Eight symptoms were reported by children during concept elicitation. Findings from the child, adolescent, and adult/parent interviews supported revisions to the items and enabled the selection of the best performing items. The results provided evidence that the final items were well understood by participants and relevant to their experiences of chest congestion as part of a common cold. Findings also provide support for using the same items across age groups. Conclusions The results of the CE and CD interviews provide evidence supporting the content validity of new PRO items assessing the experience of chest congestion symptoms associated with common cold experienced by children, adolescents, and adults.

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.

Purpose This study explored perceptions of meaningful weight-loss and the level of change on two patient-reported outcome (PRO) measures, the 36-item Short Form Health Survey® [SF-36v2®] and Impact of Weight on Quality of Life Lite-Clinical Trials © [IWQOL-Lite-CT © ], that individuals living with overweight or obesity consider to be meaningful and indicative of treatment success. Methods Thirty-three qualitative interviews were conducted in the US with adults living with overweight or obesity. Concept elicitation explored perceptions of minimally important/meaningful weight-loss using open-ended questions. Cognitive debriefing was used to understand thresholds for meaningful change on both measures. Results Most participants (n=23/33) expected a 5% total body weight-loss to yield some benefit in physical functioning, while all participants expected a 10% weight-loss to provide a meaningful and noticeable improvement in their physical functioning. Participants indicated that an item-level 1-point score change on each measure would represent a noticeable improvement in physical functioning and indicate treatment success. Conclusions Participants expected moderate weight losses to be noticeable, with ≥10% weight-loss yielding the most consistent results. The findings suggested that both measures provide strong opportunity to demonstrate treatment benefit in relation to physical functioning as a small change on the response scale would represent a noticeable improvement in participants’ daily lives.