C-Path’s Inaugural Global Impact Conference Charts the Future of Drug Development
C-Path successfully concluded its inaugural Global Impact Conference (CGIC) on September 11, 2024.
Rare Disease Cures Accelerator-Data and Analytics Platform
Overview
RDCA-DAP is an FDA-funded initiative that provides a centralized and standardized infrastructure to support and accelerate rare disease characterization with the goal of accelerating therapy development.
The Problem
Over 350 million people in the world have been diagnosed with a rare disease. In the United States, a rare disease is defined as affecting fewer than 200,000 people, and there are over 10,000 classified rare diseases. Only about 600, or 10%, of rare diseases have an FDA-approved treatment available, and drug development is frequently slowed by the low numbers of patients and limited understanding of the variability and progression of each disease.
The Solution
Critical Path Institute’s Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP®) is an FDA-funded initiative that provides a centralized and standardized infrastructure to support and accelerate rare disease characterization, with the goal of accelerating the development of treatments and cures for rare diseases. RDCA-DAP creates the collaborative, non-competitive space to share existing patient-level data and encourages the standardization of new data collection. RDCA-DAP accelerates the understanding of disease progression (including sources of variability to optimize the characterization of subpopulations), clinical outcome measures and biomarkers, and facilitates the development of mathematical models of disease and innovative clinical trial designs. RDCA-DAP is positioned to generate solutions to drug development bottlenecks through program-led solutions and facilitation of C-Path Rare and Orphan diseases consortia activities.
The Impact
The RDCA-DAP platform continues to expand since going live September 2021, and now contains data for 34 different rare disease areas, including Polycystic Kidney Disease, Duchenne Muscular Dystrophy, mitochondrial diseases, neurodevelopmental disorders, rare epilepsies and rare neurodegenerative disorders, including Friedreich ataxia. More data will be added and made accessible as outreach efforts continue.
Since the platform’s launch, we’ve seen engagement from 325 approved platform requests and 35 approved workspaces for external users and research.
The Data and Analytics Platform
RDCA-DAP houses integrated patient-level data from diverse sources, including clinical trials, longitudinal observational studies, patient registries and real-world data (e.g. electronic health records) across a multitude of rare diseases. Data are contributed from different organizations and companies around the world. C-Path has extensive experience in building such integrated databases for many diseases, including existing rare disease databases (in Duchenne muscular dystrophy, Huntington’s disease, Friedreich’s ataxia and polycystic kidney disease). C-Path has partnered with the National Organization for Rare Disorders (NORD) to leverage its IAMRARE® registry platform and extensive expertise to help identify data contributors and establish contacts with the contributing organizations. C-Path will negotiate data contribution and use agreements to allow patient-level data to be transferred to the RDCA-DAP, standardize and integrate the data with other contributed data, and make it available to the degree agreed to by the data contributors.
For questions or additional information about participating in RDCA-DAP, please email rdcadap@c-path.org.
If you’re a patient or a patient organization looking to start a registry, visit https://rarediseases.org/rdca-dap/.
Data Use
The contribution of data and subsequent access and use of the data by external users of the RDCA-DAP platform are governed by processes and agreements. These processes and documents are established to ensure patient privacy, data security, and respect data contributors’ conditions of use of their data on the platform. The Data Governance summarizes how the data provided by our contributors may be requested and accessed by users, how the decision on granting access is determined, and what is requested from users before accessing the data. In particular, once access to one or multiple datasets is authorized, users are required to sign the Data Use Agreement, a document defining the conditions, limitations and obligations for use of the data. RDCA-DAP strongly encourages data contributors to make their datasets available to users after review by our Data Use Committee. The five-member Data Use Committee is comprised of representatives of C-Path, NORD and other interested parties in the rare disease community, including patient advocacy, academic research and industry. As explained in the data governance, the committee examines users’ requests for access based on the scientific merit of the research project, educational reasons or public interest rationale, and votes as a majority to determine approval or rejections of the users’ applications.
Data Use Agreement
Access here.
Data Governance
Access here
Data Contribution Agreement, GDPR SCCs
According to the General Data Protection Regulation (GDPR), contractual clauses ensuring appropriate data protection safeguards can be used as a grounds for data transfers from the EU to third countries. This includes model contract clauses – so-called standard contractual clauses (SCCs) – that have been “pre-approved” by the European Commission.
Data Use Committee
- Alexandre Bétourné, PhD, PharmD, Data Use Committee
- Edward Neilan, MD, PhD, Data Use Committee
- Steve Roberds, PhD, Data Use Committee
- James R. Rusche, PhD, Data Use Committee
- Theresa V. Strong, PhD, Data Use Committee
Task Forces
FA-ICD
Friedreich’s Ataxia Integrated Clinical Database (FA-ICD)
Friedreich’s ataxia (FA) is a debilitating, life-shortening, degenerative neuromuscular disorder. It is the most common form of hereditary ataxia, affecting approximately 1 in every 50,000 people in the United States and Europe (FA is primarily found in white, Hispanic, and Southeast Asian populations; incidence is very rare in other racial groups). FA is an autosomal recessive, single gene disorder, caused by mutations in the FXN gene. Loss of balance and coordination is the most common presenting symptom typically beginning between the ages of 5 and 15 years with progression of symptoms leading to loss of ambulation and independence of all activities of daily living. Adult or late onset FA is less common, affecting <25% of diagnosed individuals, and can occur anytime during adulthood. While neurological features of the disease are fully penetrant, affecting 100% of those diagnosed, it is a multi-system disease. Two thirds of patients also develop cardiomyopathy, more than half develop severe scoliosis, and 10-20% develop diabetes. The mean age at death is 35 years due to cardiac complications in greater than 50% of individuals.
More information can be found at https://curefa.org
FA-ICD Mission
Launched in February 2018, the Friedreich’s Ataxia Integrated Clinical Database (FA-ICD) is designed to catalyze and accelerate Friedreich’s ataxia (FA) research and drug development by curating and standardizing FA clinical trial and natural history data into CDISC format and making this data publicly available to qualified researchers. These researchers can access and analyze data in aggregate, or filter and view individual de-identified patient-level data from four clinical trials and a large FA natural history study. Additional data may be available in the future.
FA-ICD Partnership
This initiative represents a collaborative partnership between the Friedreich’s Ataxia Research Alliance (FARA) and the Rare Diseases Cures Accelerator Data and Analytic platform (RDCA-DAP) of the Critical Path Institute (C-Path), with a goal of expanding the FA-ICD platform by engaging with other data contributors to secure additional datasets.
FA-ICD Content
FA-ICD Access and Data Contribution
FA-ICD catalogs completed FA clinical trials and natural history data and makes it available to qualified researchers. Access to the patient level data is by request only and subject to review and approval by the FA-ICD Steering Committee. To request access, you must agree to the Terms and Conditions for Use and submit a Request for Access application detailing how the data will be used, who will access the data and any plans for publishing work informed by the data. The Terms and Conditions can be accessed here.
FA-ICD encourages data contributions from interventional and non-interventional studies and is always willing to discuss how companies or other researchers can engage with the initiative. For more information on FA-ICD, including “Frequently Asked Questions” and how your organization can contribute data, please contact Alexandre Betourne, abetourne@c-path.org or rdcadap@c-path.org.
FA-ICD Solutions
The FA-ICD is currently being utilized to develop nonlinear mixed effects-based models of disease progression in FA to investigate and compare available outcome measures collected in interventional and non-interventional studies. Additionally, a placebo effect model may be incorporated to quantify the magnitude, onset, and offset of the placebo response for control arm subjects included in the FA-ICD. These models are intended to provide the foundation for a downstream clinical trial simulation tool.
Mitochondrial and Inherited Metabolic Diseases Task Force
Read about this recently-developed task force here.
Progressive Supranuclear Palsy Task Force
Read about this recently-developed task force here.
Additional Resources
For additional resources, such as a list of diseases’ data areas housed in the platform, past webinars, workshops, videos, FAQs and the FA-ICD Database, click here.
Collaborators
RDCA-DAP Data Contributors
RDCA-DAP® Collaborators
Founding Partners
Critical Path Institute is supported by the Food and Drug Administration (FDA) of the Department of Health and Human Services (HHS) and is 54% funded by the FDA/HHS, totaling $19,436,549, and 46% funded by non-government source(s), totaling $16,373,368. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government.
Team
C-Path Team
Klaus Romero, MD, MS, FCP
Chief Executive Officer, Chief Science Officer, Principal Investigator, RDCA-DAP
Collin Hovinga, PharmD, MS
FCCP, Vice President, Rare and Orphan Disease Programs
Alexandre Bétourné, PhD
PharmD, Executive Director, RDCA-DAP
Ramona Walls, PhD
Executive Director, Data Science, DCC
Heidi Grabenstatter, PhD, MS
Scientific Director, RDCA-DAP
Laura Hopkins, MS, MLS
Associate Director, Rare and Orphan Disease Programs
Dominique Cruz, MPH
Project Manager II, RDCA-DAP
Danisha Green
Project Coordinator II, RDCA-DAP
William Roddy
Data Engineer Team Lead, DCC
Diane Corey
Data Team Manager, DCC
Vicki Theurer Crider
Associate Director, DCC
Kashawna Orme
Senior Project Coordinator, DCC
NORD Team
Pam Gavin, MBA
Chief Executive Officer
Edward Neilan, MD, PhD
Chief Medical and Scientific Officer
Prashant R. Goel
Vice President, Information Technology
Rebecca Aune, MPA
Director of Education Programs
Amanda Scull, MLIS
Research Project Manager
For questions or additional information about participating in RDCA-DAP, please email rdcadap@c-path.org.