Cure Curator Platform for Rare Disease

Centralized data sets and trusted resources for rare disease patients and investigators are sparse, fragmented, and not shared among the communities they are meant to serve. Starting in a devastating rare disease, Epidermolysis Bulosa (EB), with a strategy to scale, EBRP, Stanford School of Medicine and AWS aim to unite patient phenotype and genotype data and clinical trial information in one platform, accessible to investigators, patients, and industry partners, that encourages collaboration and communication. Hosting this data, which is necessary for clinical care, disease management, and more, in a single platform with analytic capabilities for research and social connection tools for patient education and clinical trial recruitment will vastly accelerate the path to cures for rare diseases.

400 million people worldwide live with one of 7,000 rare diseases, 95% of which don’t have an FDA-approved treatment, let alone a cure. Epidermolysis Bullosa (EB), is a devastating and life-threatening genetic disorder that affects children from birth. EB is not specific to any socioeconomic status, race, ethnicity, or gender and affects an estimated 500,000 people worldwide. Like in many other rare diseases, centralized EB datasets and trusted resources for patients and investigators are sparse, hindering progress to effective therapies. For example, in 2010, EBRP established the Epidermolysis Bullosa Clinical Research Consortium (EBCRC), a group of 22 centers of excellence across North America that record EB patient data in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD). Unfortunately, the EBCCOD data is not easily accessible to investigators nor patients, is incomplete with only 44% of patients having undergone genetic analysis, and is not adequately built to efficiently connect patients with investigators and companies performing clinical research and trials. Our platform aims to collect comprehensive patient data, allowing patients themselves to directly contribute health information, and make it accessible to all stakeholders to accelerate therapy development.

Built with Amazon Web Services (AWS) and Stanford Medicine, our solution is a data platform that centralizes comprehensive patient data, resources, and clinical trial information that is accessible to EB investigators, patients, and industry partners to streamline the process of discovering cures. Investigators and patients log in to separate portals on the web or app version and navigate dashboards made specifically for their needs. Investigators can use AWS’ suite of analytic tools to evaluate patient data and research new therapies, update clinical trial information, and directly interface with patients. Patients can directly contribute their health data, request at-home genetic testing kits to pinpoint their exact mutation, be matched to specialists and clinical trials applicable to their unique condition and location, and opt in to be connected to similar patients and families. This project began with a question: what if we could make navigating the researcher and patient journey as simple as entering a destination into your GPS? Except for us, that destination is a cure.

Individuals with EB lack proteins that connect their two layers of skin, causing open external and internal wounds, disfigurement, severe pain, and more. Called “Butterfly Children” because their skin is as fragile as the wings of a butterfly, children with severe EB face shortened life expectancy, ranging from infancy to 30 years of age. There is currently no treatment or cure for EB, and parents and patients must be on constant alert for new wounds with bleach baths, drug store creams, and gauze as their only available protection against new injury and infection. Further, EB patients do not have a valid technology source for accurate information regarding their care, connection to other patients and families, and clinical trials they are eligible for. Many patients and families engage via social media groups and, while this provides a sense of community, the information is not guided by medical professionals nor is it curated to the specific needs of the individual’s disease type. EB ranges in levels of severity from life-threatening to chronic disease. Families often see information on social media that can be alarming and inaccurate without knowing how this applies to their individual condition. Additionally, these groups are not connected to trusted and easily navigable resources regarding new research and clinical trials. ClinicalTrials.gov, for example, has a wealth of information on clinical trials for EB, however its unfriendly interface and highly scientific explanations are discouraging to patients and caregivers searching for clinical trials they may be eligible to participate in, creating a barrier to study recruitment. Lastly, patients and families living with rare disease have a high willingness to partake in research and data sharing that can advance treatments and cures for their disease. However, no platform currently exists in which they can not only share data, but also receive updates that may inform their care and connection to research, clinical trials, and patients and families similar to them. 

Our data platform directly addresses these major problems facing the EB community and rare disease community at large: no effective treatments and cures, lack of access to trusted resources, and inability to partake in the research process. First, the platform will provide a comprehensive longitudinal database to doctors and researchers around the world looking to improve patient care and research therapies with potential to treat and cure this devastating disorder. Second, the platform acts as a GPS for the patient journey, connecting patients to verified information on best care practices, doctors and clinical trials near them, and similar patients to create community. Lastly, our direct-to-patient initiative allows patients to provide their own health data and even request at-home genetic testing kits, giving them agency over their care and participation in finding cures for their disease. To launch the patient-facing side of the platform, we have engaged a focus group of 25 patients and caregivers to provide feedback and frame our build to best accommodate their needs.

Lack of adequate and accessible patient datasets, collaboration among stakeholders, and validated resources are common problems in the rare disease community that thwart progress to critical treatments, cures and, ultimately, effective care. With Epidermolysis Bullosa (EB) as the use case and aspiration to scale to all rare disease, our platform will house comprehensive patient data provided by and accessible to patients and investigators alike along with clinical trial information and trusted care guidance shared via social interaction tools to improve current care and accelerate progress to treatments and cures.

Beginning as a rapid prototype build with AWS’ Envision Engineering in 2019 and advanced to a piloted project in early 2020 with Stanford University, our solution is currently running with over 500 patients enrolled and ready for data analysis by investigators. The next initiative is to launch a direct-to-patient pilot with 50 EB patients. Guided by Stanford Medicine’s Institutional Review Board (IRB) and a patient focus group, we will build a curated patient journey platform: providing at home genetic sequencing, connection to other patients, doctors, and clinical trials, and resources based on their unique disease type.

Our solution’s innovation comes from its power to centralize data and encourage collaboration, especially by giving patients agency over their own health information and care. Natural history studies, phenotype and genotype data, and biorepositories all exist in EB, however they are siloed in individual academic medical centers, limiting research breakthroughs. Pharmaceutical and biotech companies spend valuable time compiling their own natural history studies to prove their interventions in regulatory settings and identify eligible patients for trials, lengthening the process to gain drug approvals. And, most importantly, patients can only interact with the research process and receive quality care by visiting hospitals with trained staff that actively record EB-specific data, prohibiting significant support of the overall patient population, especially in a rare disease where patients are already scarce and scattered throughout the globe. Our platform tackles each of these difficulties by putting patients in the driver’s seat, able to dictate if they want to share their data, raise their hand to be contacted by clinical trial coordinators, and contact specialists or patients like them for care advice, all from the comfort of their own homes, wherever they may be in the world. The Cure Curator Platform aims to democratize exceptional care and the research process to accelerate effective treatments and cures for rare disease patients.

Built on AWS architecture by Envision Engineering and the AWS ProServ team, the Cure Curator Platform touts state-of-the-art software for data ingestion (AWS Lambda, AWS Glue), analytics (BioConda/Python/R, Amazon EC2), storage (S3 servers, AWS ElasticSearch), and reporting (AWS QuickSight) with APIs for a seamless user experience. Our genomic sequencing partner is GeneDX, founded in 2000 by two scientists from the National Institutes of Health (NIH) to address the needs of patients diagnosed with rare disorders and the clinicians treating these conditions. Today, GeneDx has grown into a global industry leader in genomics, having provided testing to patients and their families in over 55 countries. Led by its world-renowned whole exome sequencing program, and an unparalleled comprehensive genetic testing menu, GeneDx has a continued expertise in rare and ultra-rare disorders. GeneDX has a CLIA-certified gene panel test specific to EB- EB XomeDX Slice- using whole exome capture and sequencing, all of the known genes for the various forms of EB (Dystrophica, Simplex, Junctional) can be analyzed at one time, achieving substantial savings in both cost and time, with little loss of sensitivity. In most cases, this should now be the test of first choice for a new patient with the diagnosis of EB and many other rare diseases.

AWS is the trusted technology partner for major players in the healthcare industry like Illumina, CDC, Bristol-Meyers Squibb, and many more. As health data and policy requires, AWS provides unmatched security and privacy, building solutions that are regulatory compliant. Beyond basic architecture, AWS focuses on providing insights via machine learning to more quickly advance clinical research, drug discovery, as well as support personalized patient engagement. Our cloud computing suite includes existing software capabilities for Healthcare Providers & Payers, Pharma & Biotech, and Genomics. AWS’ toolkits create specific healthcare solutions to accelerate insights to improve outcomes, make data-driven decision making, and support regulatory compliance and enhance security. For specific case studies of projects built on AWS technologies, please visit https://aws.amazon.com/archite...

As with any health data, security, privacy, and compliance with regulations like the Health Insurance Portability and Accountability Act (HIPAA) are top of mind. AWS has built the Cure Curator Platform to be regulatory compliant with General Data Protection Regulation (GDPR), CA Consumer Privacy Act (CCPA), and HIPAA and has completed a data risk assessment with Stanford Medicine. The assessment ensured proper protocols for data in transit, data storage, and access including encryption. Additionally, Stanford Medicine’s Institutional Review Board (IRB) reviews all features to ensure compliance. An IRB is a designated group that reviews and monitors medical research involving human subjects to ensure their rights and welfare in accordance with FDA regulations.

Currently, the Cure Curator Platform houses data on 500 EB patients provided by Stanford Medicine through their involvement with the EBCRC and EBCCOD on the investigator-facing portal. We also plan to ingest the entire EBCCOD dataset, including 800 patients, by working with the entire CCOD. This year, we will launch the direct-to-patient initiative focused on 50 EB patients who will receive at-home genetic sequencing kits before opening enrollment to the entire EB community, which includes an estimated 500,000 individuals worldwide. After the platform is fully launched in EB in 2022, we aim to work with other rare disease groups to use it as a model for their communities. Since inception, our goal has been to build a scalable platform to support the entire rare disease population, which totals 400 million people worldwide. 

The goals of the direct-to-patient program this year are (1) to add critical genetic data that is currently missing in patients with a clinical EB diagnosis and (2) to record and analyze genetic information and clinical events to evaluate genotype-phenotype trends. In our 50 patient pilot, we will primarily enroll patients with recessive dystrophic EB (RDEB), a severe type, as there is a pronounced unmet need for increased genetic testing in this population. Previously, diagnoses were based on immunofluorescence and electron microscopy, which included subjective analysis causing inconclusive results. An accurate diagnosis is crucial for family planning purposes and clinical surveillance. Furthermore, lack of a genetic diagnosis hinders research recruitment and participation. It is estimated that over 12,500 individuals with RDEB live within the US. Cure Curator would provide all EB patients, regardless of type or location, with an opportunity for genetic diagnosis that they otherwise may not have had and enhance participation in future clinical trials. Secondly, efforts have been made to predict milestone clinical events like G-tube insertion, complete mitten deformity, and squamous cell carcinoma onset, based on subtype diagnosis to accurately and definitively counsel families about their child’s expected disease course. Genetic testing will bolster those efforts by making patient connections at the DNA level. While our 1-year goals are EB-focused, 80% of all rare diseases are genetic and can benefit from the precision of genetic testing.

Our measurements of success for our year 1 goals are (1) number of participating patients (target: 50), (2) number of referrals to clinical trials (target: 25), (3) number of surveys completed (target: 10), and (4) values of surveys (target: 50 unique clinical and patient reported fields). To reach these targets, we will remotely consent 50 patients to undergo genetic testing. A saliva test kit will be sent to the participant, along with instructions for mailing to GeneDx, our genetic testing partner. The test will be accompanied by a survey to provide clinically relevant information. An analysis of the collected genetic information along with key clinical events will be analyzed for overall trends. If our strategy is feasible, we plan to roll out this service to all EB patients globally. As new disease groups join Cure Curator, we will take learnings from our direct-to-patient initiative to guide the onboarding process.

Full-time staff: 2

Part-time staff: 4 (Stanford Team)

Contractors/Others: AWS Team, TWG UX, GeneDX

Founded by a dedicated group of parents committed to saving their children’s lives and close friends Jill and Eddie Vedder of Pearl Jam, EBRP is the leading global nonprofit funding research to discover treatments and cures for EB with over $40 million raised and 90 projects funded. Since 2010, our work has impacted the clinical landscape, leading to a 15x increase in the number of clinical trials from just 2 to over 30 today, cementing our place as a trusted source in the EB community. With the guidance of our founders and other Board and staff members who live with EB or are EB parents, the EBRP team remains driven to fulfill our mission. Additionally, expert EB clinician and researcher Dr. Jean Tang of Stanford Medicine is the principal investigator of Cure Curator. Along with her team, Dr. Tang meets with EB patients every day and is intimately aware of their medical reality and desire for a future without this devastating disorder. With Stanford Medicine as a partner, our platform will not only be effective, compliant, and poised for use by both investigators and patients, but driven by their passion to provide unmatched care to patients. Lastly, the AWS team built the architecture for Cure Curator using state-of-the-art technology, ensuring security, compliance, and innovation. Together, these three organizations ensure the mission to better patients' lives is both the primary focus and one that will be fulfilled.

At EBRP diversity, equity, and inclusion are core principles of our culture. We are member of Harvard Business School’s Kraft Precision Medicine Accelerator, a small group of CEOs of leading medical research nonprofits, that has identified addressing disparities as a core component of our work and has brought in experts to discuss how diversity, equity, and inclusion can be reflected from research recruitments to staff and Boards. 25% of EBRP’s Board is comprised of patients and patient families and one of our six employees is a patient, guaranteeing our focus on the EB community every day. Dr. Jean Tang’s lab is comprised of all female scientists at Stanford Medicine as the principal investigator and medical research team for Cure Curator. We have also engaged Dr. Ravi Hiremagalore at the Centre for Human Genetics in Bangalore, India to focus on enrollment in India as a case study for other countries with fractured healthcare systems. Through our work with Harvard Business School, we have been introduced to the group Joy Collective, a Minority Certified owned company with experience in reaching minority communities. We would seek to work with Joy Collective or a similar group to prioritize participation of underrepresented communities. We also would ensure our Patient Advisory Board was composed of a diverse group or leaders. As our platform is rolled out in other disease groups, we will continue to honor patient representation, diversity, equity, and inclusion as a core principle driving our success.

EBRP was founded by a group of patient parents set out to save their children’s lives and our staff and Board of Directors features many patients and patient family members. EBRP’s Senior Accountant Michelle Hall acts as our resident EB expert and community attaché. An inspiration to our team every day, Michelle celebrated her 34th birthday in May, surpassing her assigned life-expectancy as a person living with severe EB. The organization itself was founded by patient parents Alex and Jamie Silver and Ryan and Heather Fullmer, who rejected the 30-year life expectancy handed to their sons Jackson and Michael by dedicating their lives to finding a cure for EB. Alex acts as the Chairman of the Board and Jamie and Heather remain on our Executive Board. An additional 2 patients, 3 parents of patients, and 4 patient family members sit on our Board. While hope for a cure has increased steadily since EBRP’s founding, urgency is part of our company culture due to the closeness of our staff with the EB community.

The Horizon Prize asks “how can technology help people with rare diseases get the right care faster and more accurately?” We define “right care” not just as connecting patients to the “right” doctors or providing them the “right” products available today, but as effective treatments and ultimately cures for these patients. Since EBRP was founded in 2010 with a mission to discover treatments and cures for EB, we have funded more than 90 research projects that have impacted the clinical landscape; the number of clinical trials in EB has increased 15x from just 2 to over 30 today in only 10 years. Our work has provided hope to a deserving community of patients and families. However, we recognize that first, our mission has not yet been achieved, and second, EB is one of 7,000 rare diseases, so there are millions of other deserving patients and families out there. We see Cure Curator as both a means to accelerate research and clinical work to cure EB within this decade and also a model that can be replicated in all rare diseases to that same end. With MIT’s Solver Community as our ally, we believe we can achieve this bold goal.

We are very fortunate to have built a team with AWS and Stanford to lead development of the EB-focused version of Cure Curator. As the leading organization funding research to treat and cure EB, EBRP has partnered with esteemed organizations like Harvard Business School’s Kraft Precision Medicine Accelerator to work with and learn from other leading medical nonprofits, Mintz Levin to improve our venture philanthropy model and strengthen our research contracts, and the Milken Institute’s FasterCures to encourage continued innovation in the search for effective therapies. Although we’ve built a great team for this platform to succeed for EB, we recognize the magnitude of the vision for this project, and we want to get it right. Onboarding new patient populations is a massive undertaking that will require new researchers and patient organizations, additional engineers, and much more. MIT’s partnership would bring expertise and connections to the various areas necessary to scale this project to all rare diseases.

• Stanford Medicine Center for Definitive and Curative Medicine: Principal Investigator, Institutional Review Board (IRB), and scale to other curable rare diseases

• AWS: Cloud computing infrastructure, architecture, engineering, product design, and scale  

• GeneDX: Genomic sequencing providers leveraging CLIA-certified gene panel test specific to EB- EB XomeDX Slice- using whole exome capture and sequencing

• TWG: UX and UI design, patient surveys

• MIT Solve Members: Advisory Board and expertise

• MIT Biotech, Healthcare and Business Faculty and Initiatives: Advisory Board and expertise