Global Registry to Gather Data on Natural History of Patients With Hereditary Angioedema Type I and II
Global Registry to Gather Data on Natural History of Patients With Hereditary Angioedema Type I and II
The objective of this international hereditary angioedema (HAE) register is to collect
 homogeneous clinical and laboratory data on patients with HAE type I and II gathering better
 information on the natural course of the disease and detecting therapeutic options to manage
 it.
It is an international multicenter disease registry, the principal investigator at each
 center is responsible for competent ethic committee/institutional review board approval and
 for identifying co-investigators, who collect patients' informed consent and insert patients'
 data. Participating patients own their data. Upon acceptance of the informed consent, the
 treating physician transfers data of the case report form (CRF) to a specifically designed
 electronic support (eCRF) and the patients enter data on attacks. Physicians at center
 fill-in the eCRF with data for demography, diagnosis, prophylaxis and associated diseases.
 Plasma levels of C1 inhibitor antigen and function and of C4 antigen document laboratory
 diagnostic criteria. Each patient has a national identifier code. Patients fill-in attack
 reports that encompass duration, severity and treatment of each angioedema episode. C1
 inhibitor coding gene (SERPING1) genotype is entered according to the last Hugo nomenclature.
 Yearly update of information is recommended, patients with follow up above two years are
 moved in a separate area and excluded from analysis. Each patient prospectively fills data on
 attacks. On a specific informed consent, the patient can agree on storing biological material
 (plasma and nucleic acids) for research purposes.

 The data processor is an innovative start-up (Cloud-R s.r.l. Milan, Italy) that manages all
 data according to a specific contract and in compliance with current regulation on sensitive
 data security and processing. The Registry, delivered in the mode of Registry-as-a-Service
 (RaaS), is designed following General Data Protection Regulation (GDPR) guidelines, and
 issues regular software and infrastructure enhancements as a part of the normal operational
 mode. The system generates statistics of aggregated anonymized data following the
 participating centers' hierarchy levels and Global Registry governance rules. Patients supply
 data on attacks either on paper support or using a Web form or a mobile application. These
 data will flow into a staging area for physician validation before being considered valid for
 statistics. For each entry the system updates in real-time all the statistics and dashboards.
 The platform has configurable functionalities to support data quality management. It provides
 data format validation, integration to external qualified libraries, alerts, dashboards,
 automatic index calculations, advanced filters and queries, data change log. This open
 architecture, allows integration of the system, via standard API's, to external or
 sub-registries, registries, biobanks and clinical bioinformatics tools, i.e. for specific
 trial studies leveraging a specific cluster of patients already present in the Global
 Registry.

 An independent non-profit foundation (HGRF) made of representatives of patients' associations
 is in charge for funding and delegates all the management to the HAE Global Registry Board
 (HGRB). The HGRB is in charge for operational, assisted by the HAE Global Registry Scientific
 Committee (HGRSC) for topics of competence. No registry member, center, group or board can
 access the entire set of data. All registry members, as single or group, can propose studies
 based on aggregated data by addressing the request to the HGRSC. Analysis and studies of data
 at local centers can occur at any time. Members of HGRB and HGRSC are elected to be
 representative of different cultural and geographic backgrounds. Their offices have a
 two-year term with no more than one consecutive renewal. Angioedema centers can join the
 Registry upon request to the HGRB . The registry quality control system periodically checks
 Registry entries and compliance of eCRF with the source data. For each information, the
 system will grant traceability of time and author.
Inclusion Criteria:

 -  patients diagnosed with HAE type I and II with signed informed consent

 -  laboratory diagnostic criteria documenting plasma levels of C1 inhibitor antigen and
 function and of C4 antigen

 Exclusion Criteria:

 -  patients without HAE type I and II

 -  patients without documented laboratory diagnostic criteria

 -  patients not capable to give informed consent