Unifying Insights: A Case Study of the Global Angelman Syndrome Registry
Abstract
This case study showcases the far-reaching impact of the Global Angelman Syndrome Registry (GASR). This online, patient-driven resource is accessible to caregivers directly in their homes through a user-friendly multilingual web-based portal. Its innovative design transcends geographic and language barriers, and empowers caregivers to actively contribute, enabling greater diversity in participation than traditional registries which are limited by the availability of dedicated clinical services.
To date, over 2,000 families from nearly 100 countries have joined GASR. Since it launched in 2016, 25 organizations from around the world have partnered with GASR to help raise awareness of AS and support multilingual efforts. GASR facilitates a global AS community of stakeholders including families, patient organizations, clinicians, and researchers. Together, the community has actively created research opportunities, such as therapeutic trials, driving progress in understanding and managing AS globally.
Introduction
GASR was initiated by the Foundation for Angelman Syndrome Therapeutics Australia (FAST-AU). Meagan Cross formed the charity and registry in response to the global void in knowledge after her infant daughter was diagnosed with AS. Honey Heussler, a renowned expert in sleep and developmental paediatrics, became a principal investigator on the project and assisted with obtaining expertise and capital to support GASR. Collaborators included the Mater Children’s Hospital Foundation, who provided initial funding and support for the data curator, and the Centre for Comparative Genomics at Murdoch University, which was led by Matthew Bellgard, who provided hosting and infrastructure. Bellgard is the chair of the Asia Pacific Economic Cooperation Rare Disease Network, and co-created open-source modular registry software to capture information on rare diseases. GASR is currently maintained and hosted on the Trial Ready Registry Framework (TRRF) at Queensland University of Technology (QUT). GASR features a dynamic consent process with project information available in print and video form, multiple languages, and longitudinal data capture.
Who should benefit?
AS is estimated to affect 1 in 15,000 persons globally, with recent indications suggesting a potential prevalence of 1 in 8,000. It indiscriminately affects individuals across genders and races. Previously, research was confined to clinics in the US and Europe, with limited accessibility based on geographic and financial constraints. This posed a barrier to understanding AS comprehensively. One of the biggest obstacles faced by people with AS is a lack of awareness amongst clinicians, which results in underdiagnosis or misdiagnosis. Without an accurate diagnosis, individuals cannot access targeted treatments.
International research indicates discrepancies in diagnosis rates and time to diagnosis between countries. For example, AS prevalence studies have ranged from 1 in 10,000 persons in Denmark to 0.2 in 10,000 persons in Saudi Arabia. Geographic location may also impact the age of diagnosis. A natural history study of AS conducted in the US reported an average diagnosis age of 2 years in a sample of 302 individuals. In contrast, a Hong Kong study of 55 individuals with AS revealed an average diagnosis age of 6.2 years. Recent statistics in Australia unveiled that around 75% of potentially affected individuals may be undiagnosed or misdiagnosed; this highlights a significant gap in identifying and addressing AS on a global scale, indicating a pressing need for increased awareness, diagnostic accessibility, and healthcare equity. GASR aims to bridge these gaps, offering comprehensive global insights into the pathways to diagnosis. Care for AS patients is largely supportive and involves management of seizures and therapies to address symptoms such as communication and motor difficulties. However, tailored interventions and therapies are limited, highlighting a need for effective treatments. Further research is essential to understand the AS’s full spectrum and enable better care, patient-centred clinical trial design, and outcomes. GASR’s global, web-based, multilingual nature increases the scope for families in low- and middle-income countries to participate. Global partners in Latin America (FAST-LatAm), Italy, China, Brazil, and Poland have assisted in translating and proofreading GASR into native languages, leading to increased participation in these regions.
Engagement
Patients engage with GASR through online enrolment, providing detailed medical histories including information about symptoms, diagnoses, treatments, and the impact of AS on their lives.
Researchers and clinical professionals can utilize GASR’s extensive dataset for studies and analyses. They engage with the community by collaborating with GASR administrators, exchanging insights, and participating in forums or conferences dedicated to AS. This fosters discussions, sharing of findings, and collaboration on advancements in understanding, diagnosing, and treating AS. Users give informed consent to participate during enrolment after receiving details of GASR’s purpose, and how the data collected are used for research.
GASR has evolved significantly through patient involvement, notably by integrating patient perspectives into its structure and priorities. Patient input has influenced data-collection methods, focusing on capturing more comprehensive and relevant information about lived experiences of AS. Additionally, patient insights have driven the development of support resources and educational materials within GASR tailored to the needs and challenges of individuals with AS. This involvement has enhanced the registry’s relevance, making it more user-friendly, informative, and beneficial to the community it serves.
Patient representatives and partner researchers have been actively involved and acknowledged in communicating findings and outcomes from GASR. Their inclusion has occurred through collaborative efforts in disseminating research findings via various channels, such as scientific publications, conferences, and community forums. Contributions are explicitly recognized in publications and presentations, highlighting their vital role in shaping GASR’s outcomes and sharing its findings with the scientific community and the broader public. This acknowledgement has underscored their significance in driving the research and outcomes derived from GASR, promoting a sense of ownership and recognition within the community.
Research
GASR initially drew from a historical natural history study in US clinics and introduced standardized scales for clarity. To streamline data entry, open text fields were replaced with selectable options. Its adaptable infrastructure, managed at QUT, allows ongoing modifications in response to analysed insights and quality-assurance measures. Regular adjustments of content and format ensure ongoing relevance and user-friendliness, a process involving input from caregiver groups, researchers, and industry stakeholders. Continuous evolution guided by these engagements has profoundly shaped GASR, guaranteeing its value and adaptability as a responsive resource for AS.
Our goal is to challenge, investigate, and refine existing assumptions or prejudices prevalent in the understanding and management of AS through large-scale, globally comprehensive, and diverse data collection and analysis.
GASR endeavours to bridge critical gaps in experimental data that have impeded the delivery of appropriate diagnosis and health interventions to the global community. Historically, limited accessibility of diverse and comprehensive data on AS has hindered the development of tailored interventions. Fragmented data-collection practices, disparate healthcare systems, and the absence of centralized repositories contributed to this challenge. Additionally, insufficient data capturing the full variability of symptoms, treatment outcomes, and holistic caregiver experiences have limited the understanding of the condition’s diverse manifestations. Addressing these gaps necessitates the establishment of a comprehensive registry, collecting real-world data that encompass a wide spectrum of symptoms, treatment responses, and lived experiences across demographics and geographic regions. This effort aims to foster a more nuanced understanding of AS, facilitating the development of more tailored and effective health interventions to meet the community’s diverse needs.
GASR actively engages the affected community in each country, involving local patient organizations, researchers, and caregivers in development to give local context, disseminate project information, and assist in translations where relevant. This approach ensures research activities respect diverse perspectives and needs while gathering comprehensive data relevant to the impact of AS in various communities globally. Through these targeted engagements, GASR aims to promote inclusive, culturally sensitive, and applicable research efforts benefiting individuals affected by AS worldwide.
Ultimately, this approach aims to facilitate greater understanding of a rare disease with many complex presentations, allowing for more effective and personalized interventions, an improved diagnostic odyssey, and a deeper understanding of AS impact. This translates to real-world benefits, offering individuals and caregivers better-informed support, targeted therapies, and increased awareness, ultimately enhancing their quality of life.
