OBJECTIVES: In 2015, an online global family registry was created for the rare disease CADASIL. This study assesses whether the registry data can be used to support cross-sectional or longitudinal research studies, genetic studies, and clinical trial enrollment.
METHODS: Sample sizes and completion rates for each of the registry’s 4 surveys as well as de-identified patient-reported data were analyzed using SAS version 9.4 (Cary, NC). Outcomes are summarized using descriptive statistics. Other capabilities of the registry are described.
RESULTS: The registry includes 373 contacts worldwide, with 284 participants consenting to share de-identified survey data with researchers. Surveys were completed between June 2015 and June 2018. Among registry participants, the response rate was highest for the Diagnosis survey (n=269/284, 94.7%), followed by the Family History (n=97/284, 34.2%), General Health (n=94/284, 33.1%), and Medical Care (n=82/284, 28.9%) surveys. The number of participants responding to all 4 surveys was lower (n=66, 23.2%). Among the 284 participants, 248 (87.3%) reported being diagnosed with CADASIL, and 36 (12.7%) reported being at hereditary risk of CADASIL. Although participants are able to complete surveys more than once to provide updated data, few participants (<5) had multiple surveys completed. For genetics studies, the number of participants with uploaded genetic tests with mutation data available (for investigators interested in an IRB-approved human research study) was 13. There were 22 participants with family members in the registry, leading to 5 distinct family units. The registry contains demographic information (i.e., age, gender, country of residence, state of residence in the US, race, ethnicity), diagnosis data (e.g., age at diagnosis, time since symptom onset), and clinical co-morbidities, which could be used by the registry host to identify individuals eligible for clinical trial enrollment. Participants were aged 1 to 80 years at the time of survey completion (median=50 years, excluding 5 participants who were deceased with data provided by family members). The majority of participants live in the US (77.1%) and are female (58.8%). Nearly half of participants did not provide information on race or ethnicity; participants most commonly reported being white (33.5%) and non-Hispanic (44.0%).
CONCLUSIONS: Over 250 individuals have provided patient-reported data in the registry, allowing for identification of participants meeting broad clinical trial enrollment criteria such as demographic, diagnostic, or to a lesser extent, clinical co-morbidities (due to low response rates on the General Health survey). Clinical or genetics data from patient medical records (i.e., imaging) are not included, limiting the use. Identification of family units for familial genetic studies or participants with uploaded genetic tests is feasible, but participation remains low. For research studies utilizing de-identified, patient-reported outcomes, cross-sectional analyses of the full registry population or US population with a reported CADASIL diagnosis are currently feasible. Sample size is likely too low (<40 people) to conduct analyses of individuals at hereditary risk of CADASIL. Longitudinal analyses of the survey data are also not possible due to the low number of participants with multiple surveys over time. Low survey response rates and low number of participants updating surveys may be due to the length of surveys. Participants’ updates of each survey are critical to ensure survey data accurately represent their current health status. Survey updates would allow researchers to conduct future longitudinal studies of changes in treatment or health status over time, that are not currently possible with the existing survey data. The CADASIL Family Registry is a unique source of demographic and patient-reported outcomes for individuals with CADASIL or at hereditary risk but currently undiagnosed. Registry data can be used to support research studies requiring cross-sectional analyses, particularly of the US population with a reported CADASIL diagnosis. Sample sizes will continue to be monitored in order to alert researchers when analyses of key population subgroups or longitudinal analyses can be conducted using the registry.
