Stakeholders of Rare Diseases Informing Values In Neuroethics

Semi-structured interviews will be analyzed using MAXQDA software to identify themes though a systematic and standardized process. A deductive approach willl be used to formulate initial codes based on research questions and interview guides developed. Additional themes and codes will be developed using an inductive approach where new codes are allowed to emerge after review of the transcripts by three study team members trained in content analysis. To compensate for the multiple appearance of a code in a single interview, the percentage of patients for whom the code appeared will be tallied. Codes will be grouped and identified as a theme that captures the shared meaning. The definitions of each of the combined codes will be compared to arrive at a final definition for each theme. As with the codes, the frequency of occurrence of each theme and the percentage of patients to which each theme applied will be tallied, as well as inter-rater reliability.

Semi-structured interviews will be analyzed using MAXQDA software to identify themes though a systematic and standardized process. A deductive approach will be used to formulate initial codes based on research questions and interview guides developed. Additional themes and codes will be developed using an inductive approach where new codes are allowed to emerge after review of the transcripts by three study team members trained in content analysis. To compensate for the multiple appearance of a code in a single interview, the percentage of patients for whom the code appeared will be tallied. Codes will be grouped and identified as a theme that captures the shared meaning. The definitions of each of the combined codes will be compared to arrive at a final definition for each theme. As with the codes, the frequency of occurrence of each theme and the percentage of patients to which each theme applied will be tallied, as well as inter-rater reliability.

An interdisciplinary advisory panel of approximately 20 expert partners will be established. The panel will be presented with clearly defined problems-on elements of respect for persons (informed consent, parental autonomy), beneficence (risk-benefit assessments), justice (fair subject selection, equity) and research obligations, among others-which will be reframed to them from multiple perspectives (from results of Objective 1 and 2). The working group will engage in decisional analysis, identifying and evaluating value trade-offs through moral discussion and consensus. This iterative process of integrating normative content with empirical findings will then lead to practical recommendations, optimizing positives and minimizing negatives.

Parent and Patient-Reported Outcomes (PROs) will be quatified using the Patient Specific Functional Scale (PSFS). The parents or patient will identify five important activities that their child is having difficulty with as a result of their condition. The parent rates difficulty on an 11-point numerical scale (0= unable to perform the activity: 10= able to perform activity. The average score for the five activities is the PSFS score. (ages one month-21 years) Higher scores indicate better functional ability in patient-identified, meaningful daily activities; lower scores indicate greater functional limitation in those activities. Since the PSFS is individualized, not norm-referenced, scores are meant to track change within the same child over time, rather than functioning as a tool for interpersonal comparison.

Caregiver trust in the child's health care provider will be assessed using the Human Connection Scale. This instrument evaluates how caregivers experience meaningful relationships within the health care context, including perceived empathy, understanding, emotional support, and attentiveness of the provider. Items are rated on a Likert-type scale reflecting agreement, confidence, or frequency and are summed to produce a total human connection score. Higher scores indicate greater perceived trust and stronger caregiver-provider relationships. Trust is examined as a factor that may influence caregiver willingness to pursue highly investigational treatments.

Caregiver trust in medical researchers and the research process will be measured using the Trust in Medical Researchers scale. This instrument assesses perceptions of researcher honesty, competence, transparency, and respect for participants, reflecting caregivers' experiences of meaningful relationships within the research context. Items are rated on a Likert-type scale and summed to generate an overall trust score. Higher scores indicate greater trust in medical researchers and the research enterprise.

Caregiver resilience in the context of a child's catastrophic illness will be measured using the Connor-Davidson Resilience Scale (CD-RISC). The CD-RISC consists of 25 items assessing domains including persistence, adaptability, sense of control, optimism, coping with stress, burden, uncertainty, and fears. Items are rated on a 5-point Likert scale from 0 to 4 and summed to produce a total resilience score. Higher scores represent greater caregiver resilience.

Caregiver support needs will be assessed using the Caregiver Support Assessment Tool (CSNAT). The CSNAT is a 14-item instrument designed to identify caregiver needs across two domains: support required to enable caregiving activities and support required for the caregiver's own well-being. Each item is rated on a 4-point scale ranging from "no more support needed" to "very much more support needed." Responses are used to generate a profile of unmet support needs across domains, with higher ratings indicating greater unmet need.

Infant health-related quality of life will be measured using the PedsQL Infant Module. This parent-proxy instrument includes 36 items for infants aged 1-12 months and 45 items for infants aged 13-24 months. Subscales assess physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning. Items are rated on a Likert scale, reverse scored, and linearly transformed to a 0-100 scale. Domain and total scores are calculated as averages of item scores, with higher scores indicating better quality of life.

Health-related quality of life in children and adolescents will be assessed using the PedsQL v4.0 Generic Core Scales. This 23-item instrument includes subscales measuring physical, emotional, social, and school functioning. Items are rated on a Likert scale, reverse coded, and transformed to a 0-100 scale. Domain and total scores are calculated as averages of item scores, with higher scores indicating better quality of life. Patient self-report and parent-proxy versions are used based on age. Items not meeting internal consistency thresholds will be reported descriptively.

Disease-specific quality of life will be measured using the PedsQL 3.0 Neuromuscular Module. This 25-item instrument includes three domains: neuromuscular disease symptoms and impacts, communication about illness, and family resources. Items are rated on a Likert scale, reverse coded, and transformed to a 0-100 scale. Domain and total scores are calculated as averages of item scores, with higher scores indicating better disease-specific quality of life and family functioning. This measure will be completed only by participants with neuromuscular conditions.