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The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

Purpose: Mapping or matching the items in a clinical outcome assessment (COA) to concepts that define a condition is a common method for evaluating a COA's concept coverage. The purpose of this research was to address the lack of formal guidance for conducting this task by developing a framework for best practices in COA concept mapping and applying it to a case study. Methods: To develop the framework, we examined the literature and created a draft set of best practices which was then reviewed by experienced researchers through focus groups before being finalized. To conduct the case study, we extracted data from a systematic review of knee osteoarthritis (KO) symptoms and impacts and used the framework to map relevant concepts to items in the SF-36v2® Health Survey (SF-36v2). Results: The framework guides researchers in defining the purpose of and data sources for the mapping, establishing guiding principles and decision-making thresholds, and conducting the mapping exercise. The results of the case study demonstrate the usefulness of the framework in identifying 27/36 items (75%) in the SF-36v2 that addressed concepts that define KO. Conclusion: This case study illustrates how the framework for best practices in COA concept mapping may be used, highlighting how establishing clear concept definitions and guiding principles and following a structured process throughout can help produce consistent, reliable, and reproducible results. The results from this rigorous approach can provide valuable evidence to support decisions about the appropriateness of a COA for the intended patient population. Plain English Summary: In health-related quality of life research, mapping items in a clinical outcome assessment (COA) to concepts that define a health condition is one way to evaluate an instrument's content validity (or, how well the instrument addresses the concepts it intends to measure). Without formal guidance on how to do this mapping, researchers can be inconsistent. This article describes the development of a framework for best practices in COA concept mapping. Informed by the literature and input from researchers with expertise in COA development and evaluation, the final framework guides researchers through the mapping process from start to finish, from helping to define the purpose of the task and identify the data sources, to establishing guiding principles and decision-making thresholds, conducting the mapping, and displaying the results. A case study—in which items from the SF-36v2® Health Survey were mapped to concepts from a systematic review of knee osteoarthritis symptoms and impacts—shows the framework in action, demonstrating how following the best practices can lead to consistent results that can support the evaluation of an instrument's content validity. [ABSTRACT FROM AUTHOR]

Objective: The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content‐validated measurement tool capturing the diverse challenges of cyclin‐dependent kinase‐like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician‐reported (CCSA‐Clinician) and caregiver‐reported (CCSA‐Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability. Methods: Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in‐clinic CCSA‐Clinician evaluation (n = 148) and/or complete the CCSA‐Caregiver questionnaire (n = 198). CFA was used to determine domains, and factor loadings and validity were assessed. For the CCSA‐Clinician, inter‐rater reliability was assessed by nine CDD experienced clinicians via 14 pre‐recorded evaluations. Eight clinicians re‐viewed and re‐scored the videos after 4 weeks to evaluate intra‐rater reliability. The CCSA‐Caregiver was completed on a second occasion by 34 caregivers after 2–4 weeks to assess test–retest reliability. Results: CFA resulted in three domains for the CCSA‐Clinician (motor and movement, communication, vision) and four domains for the CCSA‐Caregiver (seizures, behavior, alertness, feeding), with good item loadings across both measures. Structural statistics, internal consistency, discriminant validity, and reliability were satisfactory for both measures, and scores were consistent between known groups. Significance: This study provides strong evidence that the CCSA measures are suitable to assess the clinical severity of individuals with CDD, supporting their use in clinical trials. Further evaluation of responsiveness to change in a longitudinal assessment is planned. Use may also be appropriate in similar DEEs but would require validation in those populations. [ABSTRACT FROM AUTHOR]

Abstract Introduction 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. Methods 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. Results 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. Conclusions 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.

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract Background The Near Visual Acuity Questionnaire Presbyopia (NAVQ-P) is a patient-reported outcome (PRO) measure that was developed in a phakic presbyopia population to assess near vision function impacts. The study refined and explored the psychometric properties and score interpretability of the NAVQ-P and additional PRO items assessing near vision correction independence (NVCI), near vision satisfaction (NVS), and near vision correction preference (NVCP). Methods This was a psychometric validation study conducted using PRO data collected as part of a Phase IIb clinical trial (CUN8R44 A2202) consisting of 235 randomized adults with presbyopia from the US, Japan, Australia, and Canada. Data collected at baseline, week 2, and months 1, 2, and 3 during the 3-month trial treatment period were included in the analyses to assess item (question) properties, NAVQ-P dimensionality and scoring, reliability, validity, and score interpretation. Results Item responses were distributed across the full response scale for most NAVQ-P and additional PRO items. Confirmatory factor analysis supported the pre-defined unidimensional structure and calculation of a NAVQ-P total score as a measure of near vision function. Item deletion informed by item response distributions, dimensionality analyses, item response theory, and previous qualitative findings, including clinical input, supported retention of 14 NAVQ-P items. The 14-item NAVQ-P total score had excellent internal consistency (α = 0.979) and high test-retest reliability (Intraclass Correlation Coefficients > = 0.898). There was good evidence of construct-related validity for all PROs supported by strong correlations with concurrent measures. Excellent results for known-groups validity and ability to detect change analyses were also demonstrated. Anchor-based and distribution-based methods supported interpretation of scores through generation of group-level and within-individual estimates of meaningful change thresholds. A meaningful within-patient change in the range of 8-15-point improvement on the NAVQ-P total score (score range 0–42) was recommended, including a more specific responder definition of 10-point improvement. Conclusions The NAVQ-P, NVCI, and NVS are valid and reliable instruments which have the ability to detect change over time. Findings strongly support the use of these measures as outcome assessments in clinical/research studies and in clinical practice in the presbyopia population.

Background: Patient‐focused outcomes present a central need for trial‐readiness across all ataxias. The Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS‐ADL) captures functional impairment and longitudinal change but is only validated in Friedreich Ataxia. Objective: Validation of FARS‐ADL regarding disease severity and patient‐meaningful impairment, and its sensitivity to change across genetic ataxias. Methods: Real‐world registry data of FARS‐ADL in 298 ataxia patients across genotypes were analyzed, including (1) cross‐correlation with FARS‐stage, Scale for the Assessment and Rating of Ataxia (SARA), Patient‐Reported Outcome Measure (PROM)‐ataxia, and European Quality of Life 5 Dimensions visual analogue scale (EQ5D‐VAS); (2) sensitivity to change within a trial‐relevant 1‐year median follow‐up, anchored in Patient Global Impression of Change (PGI‐C); and (3) general linear modeling of factors age, sex, and depression (nine‐item Patient Health Questionnaire [PHQ‐9]). Results: FARS‐ADL correlated with overall disability (rhoFARS‐stage = 0.79), clinical disease severity (rhoSARA = 0.80), and patient‐reported impairment (rhoPROM‐ataxia = 0.69, rhoEQ5D‐VAS = –0.37), indicating comprehensive construct validity. Also at item level, and validated within genotype (SCA3, RFC1), FARS‐ADL correlated with the corresponding SARA effector domains; and all items correlated to EQ5D‐VAS quality of life. FARS‐ADL was sensitive to change at a 1‐year interval, progressing only in patients with worsening PGI‐C. Minimal important change was 1.1. points based on intraindividual variability in patients with stable PGI‐C. Depression was captured using FARS‐ADL (+0.3 points/PHQ‐9 count) and EQ5D‐VAS, but not FARS‐stage or SARA. Conclusion: FARS‐ADL reflects both disease severity and patient‐meaningful impairment across genetic ataxias, with sensitivity to change in trial‐relevant timescales in patients perceiving change. It thus presents a promising patient‐focused outcome for upcoming ataxia trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and Aims: Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease‐modifying therapies including genetic therapies. The Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS) is a well‐validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD. Methods: The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children's Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS. Results: CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. 'Shoulder internal rotation' and the '30‐s sit to stand test' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single 'Feet apart on a line eyes open' balance item. 'Pinprick sensation' was removed due to a floor effect. Interpretation: This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcome measures (PROMs) are used to collect data on disease symptoms in support of clinical trial endpoints. Clinical studies can last a year or more, and the patients' adherence and response time to daily at-home questionnaires may vary significantly over time. The aim of this study was to understand patterns and changes in patients' completion of daily PROMs during longitudinal clinical studies. Methods: Data were collected from 1342 patients randomized into three respiratory clinical trials (NCT03401229, NCT03347279, and NCT03406078). PROMs were completed by patients using electronic handheld devices that collected the starting and completion times. A Bayesian generalized linear mixed-effects model was used to identify unbiased coefficients associated with PROM adherence and response time using patient, site, and calendar features as covariates. Results: Adherence decreased over time after randomization, and the rate of decrease was higher in younger patients. The 14-day pre-randomization adherence was correlated with adherence throughout the study. Patients were also more adherent during working days compared to non-working days. Oldest patients took twice as long to complete PROMs throughout the study; however, the response time for all patients decreased during the first month of the study regardless of age. Response time increased 7 days before and after the date of a scheduled clinic visit and when a patient-reported higher symptom burden. Conclusion: Detailed analyses of adherence and response time for daily PROMs in clinical trials can provide significant insights about trends of patient behavior in longitudinal clinical studies with high baseline adherence. [ABSTRACT FROM AUTHOR]

Purpose: To identify symptoms and their impacts on daily functioning and health-related quality of life (HRQoL) experienced by adult patients with ulcerative colitis (UC) and evaluate patient-reported outcome (PRO) measures for UC clinical studies. Methods: A conceptual model of symptoms and impacts of UC were developed from a literature review. PRO measures were identified from the literature, clinical trials databases, health technology assessment submissions, and regulatory label claims, and were selected for conceptual analysis based on disease specificity and use across information sources. PRO measures covering the most concepts when mapped against the conceptual model were assessed for gaps in psychometric properties using Food and Drug Administration (FDA) guidance and consensus-based standards for the selection of health measurement instruments (COSMIN) criteria. Results: The conceptual model grouped the 52 symptom concepts and 72 proximal and distal impacts into eight, two, and five dimensions, respectively. Of 65 PRO measures identified, eight underwent conceptual analysis. Measures covering the most concepts and assessed for psychometric properties were the Inflammatory Bowel Disease Questionnaire, Symptoms and Impacts Questionnaire for UC, UC-PRO symptoms modules, UC-PRO impact modules, and Crohn's and UC Questionnaire; all had good or excellent support for content validity. The UC-PRO Signs and Symptoms fully met FDA guidance and COSMIN criteria for content validity and most psychometric properties. Conclusion: Existing PRO measures assess concepts relevant to patients with UC, but all PRO measures reviewed require further psychometric evaluation to demonstrate they are fit for purpose. [ABSTRACT FROM AUTHOR]

To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials. • Irritable Bowel Syndrome (IBS) is a chronic functional bowel disorder characterized by recurrent episodes of abdominal pain associated with alterations in bowel movements. • The Diary for IBS Symptoms-Constipation was developed to support primary and key secondary endpoints in clinical trials for the treatment of IBS with predominant constipation. • The results of this study provided key psychometric evidence for the Diary for IBS Symptoms-Constipation, ultimately contributing to the qualification of this measure by the US Food and Drug Administration in 2020 for use in IBS with predominant constipation clinical trials. [ABSTRACT FROM AUTHOR]

Rationale: A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life among patients with chronic obstructive pulmonary disease (COPD) that is not fully accepted in regulatory decision making, hampering drug development. Objectives: To demonstrate, as we previously asserted (Casaburi COPD 2022;9:252), that constant work rate cycling endurance time is an appropriate exercise endurance measure in patients with COPD. Methods: To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2,166 subjects) and 15 exercise training (3,488 subjects) studies (Casaburi COPD 2022;9:520). Results: Construct validity was demonstrated: 1) peak physiologic and perceptual responses were similar for constant work rate and incremental cycling; 2) after bronchodilator therapy, there were greater increases in endurance time in patients with more severe airflow limitation; 3) after exercise training, endurance time increases were similar across airflow limitation severities; and 4) there were correlations between changes in endurance time and changes in mechanistically related physiologic and perceptual variables. Test–retest reliability was demonstrated, with consistency of changes in endurance time at two time points after the intervention. Responsiveness was confirmed, with significant increases in endurance time after active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation and after exercise training. On the basis of regression analysis using multiple anchor variables, the minimum important difference for endurance time increase is estimated to be approximately 1 minute. Conclusions: Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to the evaluation of treatment benefit supporting regulatory decision making and evidence-based therapeutic recommendations. [ABSTRACT FROM AUTHOR]

Background: The Near Visual Acuity Questionnaire Presbyopia (NAVQ-P) is a patient-reported outcome (PRO) measure that was developed in a phakic presbyopia population to assess near vision function impacts. The study refined and explored the psychometric properties and score interpretability of the NAVQ-P and additional PRO items assessing near vision correction independence (NVCI), near vision satisfaction (NVS), and near vision correction preference (NVCP). Methods: This was a psychometric validation study conducted using PRO data collected as part of a Phase IIb clinical trial (CUN8R44 A2202) consisting of 235 randomized adults with presbyopia from the US, Japan, Australia, and Canada. Data collected at baseline, week 2, and months 1, 2, and 3 during the 3-month trial treatment period were included in the analyses to assess item (question) properties, NAVQ-P dimensionality and scoring, reliability, validity, and score interpretation. Results: Item responses were distributed across the full response scale for most NAVQ-P and additional PRO items. Confirmatory factor analysis supported the pre-defined unidimensional structure and calculation of a NAVQ-P total score as a measure of near vision function. Item deletion informed by item response distributions, dimensionality analyses, item response theory, and previous qualitative findings, including clinical input, supported retention of 14 NAVQ-P items. The 14-item NAVQ-P total score had excellent internal consistency (α = 0.979) and high test-retest reliability (Intraclass Correlation Coefficients > = 0.898). There was good evidence of construct-related validity for all PROs supported by strong correlations with concurrent measures. Excellent results for known-groups validity and ability to detect change analyses were also demonstrated. Anchor-based and distribution-based methods supported interpretation of scores through generation of group-level and within-individual estimates of meaningful change thresholds. A meaningful within-patient change in the range of 8-15-point improvement on the NAVQ-P total score (score range 0–42) was recommended, including a more specific responder definition of 10-point improvement. Conclusions: The NAVQ-P, NVCI, and NVS are valid and reliable instruments which have the ability to detect change over time. Findings strongly support the use of these measures as outcome assessments in clinical/research studies and in clinical practice in the presbyopia population. [ABSTRACT FROM AUTHOR]

Abstract Background Over the past few decades, patient-reported outcomes (PROs) have been used to understand patient health conditions better. Therefore, numerous PRO measures (questionnaires) and guidelines or guidance have been developed. However, it is challenging to select target guidance from among the many available guidance and to understand the chosen guidance. This study comprehensively collected the existing PRO guidance for clinical trials or studies and practices to support novice PRO users in academia, industry, clinical practice, and regulatory and reimbursement decision-making. Methods For the scoping review, we searched the MEDLINE, Embase, Google Books, WorldCat, and the National Library of Medicine (NLM) Bookshelf databases from 2009 to 2023. The eligibility criteria were PRO guidance for clinical trials, clinical practice, or application such as health technology assessment. Those guidance cover aspects such as quality of life (QOL), PRO, health-related QOL, health state utilities, psychometric requirements, implementation methods, analysis and interpretation, or clinical practice applications. After the systematic search, three researchers individually reviewed the collected data, and the reviewed articles and books were scrutinized using the same criteria. Results We collected the PRO guidance published in articles and books between 2009 and 2023. From the database searches, 1,455 articles and 387 books were identified, of which one book and 33 articles were finally selected. The collected PRO guidance was categorized into the adoption of PRO measures, design and reporting of trials or studies using PROs, implementation of PRO evaluation in clinical trials or studies or clinical practice, analysis and interpretation of PROs, and application of PRO evaluation. Based on this categorization, we suggest the following for novices: When selecting guidance, novices should clarify the “place” and “purpose” where the guidance will be used. Additionally, they should know that the terminology related to PRO and the scope and expectations of PROs vary by “places” and “purposes”. Conclusions From this scoping review of existing PRO guidance, we provided summaries and caveats to assist novices in selecting guidance that fits their purpose and understanding it.

Abstract 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.

Study Objectives: Sleep difficulties are common in CDKL5 deficiency disorder, a developmental and epileptic encephalopathy. This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Somnolence (DOES), and Sleep Breathing Disorders domains of the Sleep Disturbance Scale for Children for CDKL5 deficiency disorder., Methods: A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a United States Centers of Excellence clinic or registered with the International CDKL5 Disorder Database., Results: The median age was 10.3 years (range 3.2-40.7 years) and 105 (84%) were female. Two of the 3 Sleep Breathing Disorders items were not observed by most respondents and analysis was restricted to the DIMS and DOES domains. Using all items in the initial confirmatory factor analysis, 2 items in the DIMS domain and 1 item in the DOES domain loaded poorly. After deleting these items and repeating the analysis, item loading (.524-.814) and internal consistency (DIMS: .78, DOES: .76) statistics were good. The square of the interdomain correlation coefficient was .17, less than average variance extracted values for both domains and indicating good discriminant validity. The Tucker-Lewis and Comparative Fit indices were slightly lower than the threshold of > .9 for establishing goodness of fit., Conclusions: The modified DIMS and DOES domains from the Sleep Disturbance Scale for Children could be suitable clinical outcome assessments of insomnia and related impairments in CDKL5 deficiency disorder and potentially other developmental and epileptic encephalopathy conditions., Citation: Saldaris JM, Demarest S, Jacoby P, et al. Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study. J Clin Sleep Med . 2024;20 (12):1887-1893., (© 2024 American Academy of Sleep Medicine.)

Background: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, neurodegenerative disorder with no disease-modifying treatments. There is a dearth of information in the literature about the patient and caregiver experience living with DRPLA., Objectives: This study aimed to (1) understand symptoms experienced by adult- and juvenile-onset DRPLA populations and their impact on daily life and (2) explore patient and caregiver treatment goals and clinical trial participation preferences., Design: The study was a qualitative interview study., Methods: Interviews were conducted remotely with adult patients with DRPLA and caregivers. Participants described patient symptoms and the impact of those symptoms on daily life, and they discussed treatment goals and potential clinical trial participation. There were 18 patients described in the interviews with two patients and seven caregivers. Some participants were caregivers to multiple patients with DRPLA., Results: Interview transcripts were coded for themes, and reported symptoms were summarized with descriptive statistics. Adult-onset patients ( N  = 7) experienced difficulty with ataxia (100%), cognition (100%), fine motor skills (100%), gross motor skills (100%), speech (100%), personality changes (100%), and seizures (57%). Juvenile-onset patients ( N  = 11) experienced difficulty with ataxia (100%), sleep (100%), speech (100%), jerking/twitching (83%), behavior (82%), cognition (82%), fine motor skills (82%), gross motor skills (82%), sensory sensitivity (75%), and seizures (64%). When considering aspects of DRPLA to target for future treatment, patients prioritized ataxia/mobility (100%), juvenile-onset caregivers prioritized ataxia/mobility (60%) and independence (60%), and adult-onset caregivers prioritized personality (60%). Almost all patients (93%) would participate in a clinical trial if given the opportunity, but travel to a clinical site could pose a participation barrier for half., Conclusion: This study found that there are symptom domains that are relevant across the DRPLA population, but there is heterogeneity within each domain based on the age of symptom onset and disease stage, which has implications for clinical trial design., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

The experience of migraine symptoms and the impacts of migraine on quality of life (QOL) are best reported by the person experiencing them. Therefore, patient-reported outcome (PRO) measures are often used to collect data about the experience and impact of migraine, and value of migraine treatments. PRO concepts that are assessed for the evaluation of migraine treatment outcomes are myriad and diverse (e.g., symptoms, impacts, satisfaction). The first step toward developing a precise strategy to evaluate the outcomes of a treatment is identifying WHAT to measure. This is followed by considerations around HOW to measure the concept. "Selecting What to Measure" section of this chapter discusses the important PRO concepts (WHAT) to measure the impact of migraine and to evaluate interventions for migraine. "Selecting How to Measure" section of this chapter focuses on HOW to collect data about these outcomes in the context of research to evaluate migraine treatments. PRO endpoints recommended in international migraine guidelines and examples of PRO measures that can be used for collecting data to support these endpoints are discussed. The final section of this chapter suggests considerations for selecting PRO measures for evaluating the impact of migraine and migraine treatments and for using these measures to collect data in clinical research., (Copyright © 2024 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)