UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The study was a qualitative interview study.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
Understanding dentatorubral-pallidoluysian atrophy (DRPLA) symptoms and impacts on daily life through interviews with patients and caregivers Why was the study done? Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare and progressive brain disorder. Little is known about the patient and caregiver experience living with DRPLA and this lack of information has hindered the development of patient-focused treatments and the measurement of outcomes that are most meaningful to caregivers and patients. What did the researchers do? To address this problem, researchers conducted interviews with patients and caregivers of DRPLA to (1) better 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. What did the researchers find? Eighteen patients were described in the interviews. Adult-onset patients (onset at age 20 or older) experienced difficulty with coordination, cognition, motor skills, speech, personality changes, and seizures. Juvenile-onset patients (onset before age 20) experienced difficulty with coordination, sleep, speech, jerking/twitching, behavior, cognition, motor skills, sensory sensitivity, and seizures. When considering symptoms to prioritize for future treatment, patients and caregivers identified coordination/mobility, independence, and personality as important. Nearly all participants indicated they would participate in a clinical trial if given an opportunity, however half expressed that travel to a clinical site could pose a barrier. What do the findings mean? This study provides a better understanding of the symptoms experienced by DRPLA patients and their impact on daily life. Additionally, it identifies important targets for treatment and considerations when designing clinical trials for DRPLA such as the barrier caused by travel to a clinical site.

Digitized assessments have a considerable potential to guide clinicial decision making and monitor progress and disease trajectories. The Timed Up and Go test (TUG) has been long established for assessment in geriatric medicine and instrumented versions (iTUG) have been developed and validated. This scoping review includes studies that applied the iTUG and aims to identify use cases to show where and how iTUG assessment could guide interventions and clinical management. The literature search was limited to peer-reviewed studies that performed pre- and post-intervention measurements with a 3-meter TUG instrumented with body-worn technology in samples of at least 20 subjects aged 60+ years. Of 3018 identified articles 20 were included. Four clinical use cases were identified: stratification for subsequent therapy, monitoring of disease or treatment-associated changes and evaluation of interventions in patients with idiopathic normal pressure hydrocephalus (1), and patients with Parkinson\'s disease (2); monitoring after joint replacement surgery (3), and evaluation after different exercise and rehabilitation interventions (4). The included studies show diversity in terms of iTUG technology and procedures. The identified use cases highlight clinical relevance and high potential for the clinical application of the iTUG. A consensual approach as well as comprehensive reporting would help to further exploit the potential of the iTUG to support clinical management. Future studies should investigate the benefits of segmental iTUG analysis, responsiveness and participants\' perspectives on clinically meaningful changes in iTUG.

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: 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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.

The US Food and Drug Agency (FDA) requires clinical trials targeting cognitive impairment associated with schizophrenia (CIAS) to demonstrate the functional relevance of cognitive improvements by employing a functional co-primary measure. Although quantitative evidence supports the suitability of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for this purpose, FDA guidelines for qualification of clinical outcome assessments require evidence of content validity, defined as qualitative evidence that key stakeholders view the measure as relevant and important. To collect this important qualitative data, semi-structured interviews were conducted with outpatients with schizophrenia (n = 24), caregivers (n = 12), and professional peer support specialists (n = 12) to elicit their views about the definition and importance of functional independence, the importance of the functional domains assessed by the VRFCAT (meal planning, using transportation, handling money, shopping), and the relevance of the VRFCAT tasks to these domains. Qualitative thematic analyses revealed consistent themes across groups in defining functional independence, including performing instrumental self-care, financial, and social tasks; making decisions autonomously; and not depending on others to carry out daily activities. There were, however, notable differences in their views regarding the importance of and barriers to functional independence. All groups viewed the VRFCAT as assessing skill domains that are central to independent functioning and, with some minor differences, the VRFCAT tasks were viewed as relevant and meaningful examples of the domains. These qualitative results provide converging evidence that key stakeholders view the VRFCAT as a content-valid measure.

BACKGROUND: In support of UCB pharmaceutical research programs, the aim of this research was to implement a novel process for patient involvement in a multidisciplinary research group to co-create a clinical outcome assessment strategy to accurately reflect the experience of people living with early-stage Parkinson\'s. Patient experts were an integral part of the decision-making process for patient-reported outcome (PRO) research and instrument development.
METHODS: In partnership with two patient organizations (Parkinson\'s UK and the Parkinson\'s Foundation), 6 patient experts were recruited into a multidisciplinary research group alongside clinical, patient engagement and involvement, regulatory science, and outcome measurement experts. The group was involved across two phases of research; the first phase identified what symptoms are cardinal to the experience of living with early-stage Parkinson\'s and the second phase involved the development of PRO instruments to better assess the symptoms that are important to people living with early-stage Parkinson\'s. Patient experts were important in performing a variety of roles, in particular, qualitative study protocol design, conceptual model development, and subsequent co-creation of two PRO instruments.
RESULTS: Involving people with Parkinson\'s in PRO research ensured that the expertise of these representatives from the Parkinson\'s community shaped and drove the research; as such, PRO instruments were being developed with the patient at the forefront. Working with patient experts required considerable resource and time allocation for planning, communication, document development, and organizing meetings; however, their input enriched the development of PRO instruments and was vital in developing PRO instruments that are more meaningful for people with Parkinson\'s and clinicians.
CONCLUSIONS: Conducting PRO research, in the context of clinical development involving pharmaceutical companies, requires balancing regulatory and scientific rigor with tight time constraints. Incorporating a multi-stakeholder perspective, which included patient experts as joint investigators, had a strong positive impact on our research, despite the logistical complexities of their involvement. Due to the input of patient experts, the innovative clinical outcome assessment strategy and the co-created novel PRO instruments were more relevant and holistic to the patient experience of early-stage Parkinson\'s.
Patient-reported outcome (PRO) instruments allow people living with a disease and participating in a clinical study to describe the symptoms and experiences that they consider meaningful. PRO instruments use tools such as questionnaires and scales to capture patient perspectives on a treatment that might not be captured by a clinical measurement. It is recommended that the patient community and patient experts are included in the development of PRO instruments to accurately capture information that is important to them. Building on the experience of a recent PRO research project in support of UCB pharmaceutical programs, this article provides recommendations on how pharmaceutical companies can partner with patient organizations and involve patient experts as joint investigators in the co creation of PRO instruments. Despite the additional resource and time required, involving patient experts and patient organizations into the research collaboration had a strong positive impact and ensured that the PROs were meaningful to patients (in this instance, people living with early-stage Parkinson’s). Patient organizations facilitated patient engagement and recruitment in research activities, maintained communication with the pharmaceutical company’s research team, and built trust between collaborators by implementing patient engagement tools and best practices. Patient experts contributed to several parts of the PRO instrument development process: study design, identifying key symptoms and experiences, and developing individual PRO questions. Co-creation between the pharmaceutical company, patient experts, and patient organizations resulted in considerable improvements to typical PRO instrument development for use in clinical trials and is thus recommended.

UNASSIGNED: Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative diseases in which little is known about the most appropriate clinical outcome assessments (COAs) to capture disease progression. The objective of this study was to prospectively determine disease progression after 4.5 years of follow-up with different clinician-reported (ClinRO) and gait performance outcomes (PerFOs).
UNASSIGNED: Twenty-six HSP patients (15 SPG4, 5 SPG7, 4 SPG5, 2 SPG3A) participated in this single-center cohort study in which the ClinRO: Spastic Paraplegia Rating Scale; and the PerFOs: 10-meters walking test and timed-up and go (TUG), at self-selected and maximal walking speeds; Locomotor Rehabilitation Index; and 6-min walking test were performed at baseline and after 1.5 (18 patients) and 4.5 (13 patients) years.
UNASSIGNED: In the 3-year interval between the second and third assessments, significant progressions were only found in PerFOs, while in the overall 4.5 years of follow-up, both PerFOs and ClinROs presented significant progressions. The progression slopes of COAs modeled according to the disease duration allowed the estimation of the annual progression of the outcomes and sample size estimations for future clinical trials of interventions with different effect sizes. TUG at maximal walking speed was the only COA capable of differentiating subjects with a worse compared to a stable/better impression of change and would require the smallest sample size if chosen as the primary endpoint of a clinical trial.
UNASSIGNED: These findings indicate that both performance and clinician-reported outcomes can capture long-term progression of HSPs, with some PerFOs presenting greater sensitivity to change. The presented data are paramount for planning future disease-modifying and symptomatic therapy trials for this currently untreatable group of diseases.

BACKGROUND: Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) are rare inherited retinal degenerative disorders. The associated visual impairments have significant impacts on patients\' vision-dependent activities of daily living (ADL), mobility, and distal health-related quality of life (HRQoL). To adequately capture patient and caregiver perspectives in clinical trials, patient and observer-reported outcome instruments must demonstrate sufficient evidence of content validity in the target population. This study aimed to explore the patient experience of RP/LCA and assess the content validity of the Visual Symptom and Impact Outcomes PRO (ViSIO-PRO) and ObsRO (ViSIO-ObsRO) instruments in RP/LCA.
METHODS: A total of 66 qualitative, combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted (33 adults, 10 adolescents, 8 children and 15 caregivers of children) in the US, France, Germany, and Canada. Patients had a clinical and genetic diagnosis of RP/LCA from a range of genotypes. CE results were used to further inform the development of a conceptual model and CD interviews assessed the relevance and understanding of the 44-item ViSIO-PRO and 26-item ViSIO-ObsRO instruments. Interviews were conducted across two iterative rounds to allow item modifications.
RESULTS: Findings were consistent across RP/LCA genotypes. Night blindness, reduced peripheral vision, vision in very bright lighting and light/dark adaptation were the most frequently reported visual function symptoms impacting vision-dependent ADL and mobility. Impacts on distal HRQoL domains were also reported. The ViSIO-PRO and ObsRO items were well understood by participants and relevant across genotypes. The instructions, 7-day recall period and response scales were well understood and endorsed. Participant and expert clinician feedback supported modifications to item wording, the addition of six new ViSIO-PRO items and one new ViSIO-ObsRO item, and the removal of one ViSIO-PRO item due to lack of relevance.
CONCLUSIONS: Findings support the content validity of the ViSIO-PRO and ViSIO-ObsRO instruments for use across RP/LCA genotypes. Ongoing research to evaluate the psychometric validity of the instruments will support future use of the instruments as efficacy endpoints in clinical trials and in general clinical practice to track disease severity and impact of disease on functioning.