Study design

We conducted a cross-sectional online survey of adult family caregivers for individuals with AS residing in the US. Caregivers were asked about several areas of life that could be impacted by caregiving, including household expenses related to accommodations or care, healthcare costs for caregivers, employment-related impacts, lost leisure time, and quality of life impacts. Responses were used to estimate the annual economic cost of these impacts to caregivers. The survey did not gather information on direct medical care costs borne by healthcare insurers or other economic impacts to the US government and other stakeholders.

Survey development

The survey was developed with input from the Foundation for Angelman Therapeutics (FAST), the Angelman Syndrome Foundation (ASF), caregivers of individuals with AS, academic clinical experts, and representatives from pharmaceutical and biotechnology companies with AS therapies in development [17, 18]. Both qualitative and quantitative piloting was conducted with caregivers to develop the survey instrument and confirm instrument validity.

Data collection

The survey was embedded as a module within the Global Angelman Syndrome Registry (GASR), an internet-based disease registry that collects data from parents and caregivers regarding the natural history and management of AS [19, 20]. For individuals with AS represented in the survey, some demographic and clinical data (e.g., AS genotype) were gathered from the GASR database. The design and implementation of the module within the GASR database was supported by the GASR Governance Board. Ethical approval to conduct this study was provided by Mater Research and the GASR Governance Board, which oversees research access to de-identified registry data. Informed consent was obtained from all caregivers prior to initiation of the survey.

Survey recruitment

Survey respondents were recruited through networks maintained by FAST and ASF. The survey sample was restricted to individuals who voluntarily cared for an individual with AS for the past twelve months, could provide estimates of the costs and impacts of the care they provided, were age ≥ 18 years, resided in the US, and were registered in the GASR during the study recruitment period (December 2022 through May 2023). To be included in the analytical sample, caregivers were required to complete the survey, defined as answering the final survey question. Outreach was conducted through the GASR database to encourage caregivers with partial survey responses to complete the survey.

Survey componentsDemographic and clinical characteristics

Caregivers provided sociodemographic information for themselves and for the person with AS for whom they provided care. Caregivers also provided details regarding their caregiving role and responsibilities, such as their relationship to the person with AS, whether they identified as a primary, secondary, or split-duty caregiver, and the number of years spent providing care. Additionally, they provided details regarding the caregiving needs of the person with AS, including hours per day of care received in the past week, level of professional caregiving needed, and whether they could be left alone for periods of time.

Household costs to accommodate and care for individuals with AS

Household costs for AS-related accommodations and care were captured for items in the following categories: home modifications or repairs, vehicle purchases or modifications, medical equipment purchases, long-term care, professional caregiving, supportive therapy, school or educational expenses, and out-of-pocket healthcare expenses (e.g., out-of-pocket costs for outpatient visits or prescription drugs). For each item, caregivers were asked to report their household’s total AS-related expenditures in the past twelve months. Caregivers were asked to provide their best estimate of the costs that were specifically paid by their households (e.g., credit card, cash, family savings), not including any costs paid by external sources (e.g., health insurance, government, or charitable organizations). Caregivers were asked to provide their best estimate of costs that were incurred as a direct result of the care recipient’s AS condition.

Caregiver healthcare costs

Caregivers were asked if they had received any pharmaceutical treatments or medical care in the past twelve months as a result of caregiving for a person with AS. If so, caregivers were asked how much they had spent out of pocket over the past twelve months. Caregivers were asked to provide their best estimate of costs that were incurred as a direct result of the care recipient’s AS condition.

Caregiver employment-related impact

Caregivers were asked about changes in work status, working hours, or productivity during working hours as a result of caregiving for the person with AS. Questions related to days of missed work and work productivity loss among employed individuals were included from the caregiver version of the Work Productivity and Activity Impairment (WPAI) questionnaire [21].

Caregiver leisure time impact

Caregivers were asked to estimate average leisure time loss per week as a result of their caregiving responsibilities. Questions for estimating leisure time loss were derived from the iMTA Valuation of Informal Care Questionnaire (iVICQ) [22].

Caregiver quality of life

Caregivers were asked several questions about their own quality of life and how it might be impacted by caregiving. Caregivers provided a self-assessment of their caregiving situation derived from the Care-related Quality of Life instrument (CarerQol), an instrument that is included as part of the iVICQ questionnaire [22]. The choice of quality of life questions was derived based on stakeholder input and qualitative piloting to ensure that quality of life questions were representative of experiences for US caregivers of individuals with AS. The CarerQol instrument has also been used extensively in prior research to assess quality of life impacts for caregivers of other pediatric populations [23,24,25,26].

Additional File 1 includes additional information for each category of impact.

Statistical analysesDemographic and clinical characteristics

Characteristics were summarized separately for caregivers and persons with AS for whom they provided care. Categorical variables were summarized using frequencies and percentages, while continuous variables were summarized using means and standard deviations (SD).

Household costs to accommodate and care for individuals with AS

The number and proportion of caregivers reporting an expense in the past twelve months were reported for each cost category. Costs were summarized in terms of means and SDs for each cost category and overall. Additional File 1 includes additional information.

Caregiver healthcare costs

The number and proportion of caregivers reporting caregiving-related healthcare expenses in the past twelve months were reported. Costs were summarized for pharmaceutical, medical, and combined healthcare expenses in terms of means and SDs.

Caregiver employment-related impact

The annual economic value of lost work productivity was estimated by multiplying the mean (SD) reported weekly hours of lost work productivity by a nationally representative hourly wage ($33.74 as of July 2023) [27], and further multiplying by 52 weeks per year. Calculations were conducted separately for the three components of employment impact due to caregiving demands (early retirement, reduced working hours, reduced work productivity) as well as overall.

Caregiver leisure time impact

The annual economic value of lost leisure time was estimated using similar methods to lost work productivity, with each hour of leisure loss valued at 35% of the national hourly wage, consistent with methods from prior caregiver research [28].

These components of caregiver impacts were added together to estimate the total annual economic impact of caregiving associated with AS. Annual caregiver impacts were also descriptively summarized by the age of individuals with AS (0 to 5, 6 to 12, 13 to 17, and 18 +). Other survey outcomes were summarized in terms of proportions and depicted graphically. Additional File 1 contains additional details regarding methods for study calculations.