Cross TA Teams Head, Global Epidemiology Janssen Allschwil, Switzerland
Background: In rare diseases such as Pulmonary Arterial Hypertension (PAH), real-world (RW) evidence generation is often restricted due to the small patient population, geographic distribution, and limited data accessibility. The federated data networks (FDNs) approach brings together multiple disease-specific fit-for-purpose data sources to increase the observational power of research projects. The Pulmonary Hypertension (PH) FDN, called PHederation, is a public private partnership.
Objectives: To describe how PHederation can facilitate fit-for-purpose data source evaluation and facilitate scientific collaboration in rare disease.
Methods: In PHederation each database owner remains in full control regarding the use of and access to patient-level clinical data and is responsible for data privacy, ethics and legal compliance. Each database has a representative on the highest governance body - the PHederation Board. To harmonize data, each database is transformed into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), with addition of custom rules specific to PH- and registry mapping (Handbook for PH registries to OMOP CDM conversion https://github.com/OHDSI/ETL--PulmonaryHypertensionRegistries). High-level aggregate information on patient characteristics and clinical assessments for each database are available for PHederation partners, allowing fit-for-purpose and feasibility assessments of the databases for identified research questions. For each of the selected databases, aggregate results are provided by the partners according to the common protocol and analysis plan. Finally, network meta analyses and results interpretation are performed across all selected datasets.
Results: To date, PHederation consists of 6 databases from North America and Europe, covering 12’296 confirmed PH patients, of whom 78% are PAH patients: - 3 PH registries: Canadian PH Registry (N=1’995; 54% PAH), Porto Center (N=578; 37% PAH), Stanford (N=1’189; 83% PAH) - International PAH cohort study EXPOSURE (EUPAS19085; N=2’000; 100% PAH) - 2 US drug registries: OPUS/ORPHEUS (NCT02126943/ NCT03197688; N=5’705; 81% PAH), SPHERE (NCT03278002; N=829; 92% PAH).
Conclusions: PHederation FDN established a network of relevant databases of diverse purpose and origins but a common goal – to advance scientific knowledge of PH. The platform allows for fit-for-purpose assessment which facilitates selection of the largest possible patient cohort for each research question, assessment of heterogeneity and identification of potential selection and other biases to be addressed. PHederation expands the breadth and depth of individual PH databases to increase evidence generation.
