Table 1.

The EPIRARE set of common data elements for the European RDR platform

	COMMON DATA ELEMENTS collected in the EPIRARE platform (elements in bold require longitudinal data collection)	ANNOTATIONS regarding the data elements; Where indicated: DEFINITIONS and FORMATS	REASON
Domain 1) Case characterization essentials
Case notification - Mandatory data	EU Global Unique Identifier (EU GUID)	This code is elaborated from the following data elements:	Unambiguous patient coding (to be processed according to legal provisions) is necessary to keep the integrity of the database and avoid duplication of records.
		• Patient given name: DEFINITION: “First name of patient as recorded in birth certificate, passport or identity card”; FORMAT: full name, not initials
		• Patient family name (at birth): DEFINITION: “Family name of patient as recorded in birth certificate, passport or identity card”; FORMAT: full name, not initials	The National Unique Identification Code increases the accuracy of the EU GUID in case of names in foreign languages. It could be an optional part of the encrypted code.
		• Patient sex: see definition below
		• Patient date of birth: see definition below
		• Patient city of birth: see definition below
		National Unique Identification Code
	Patient sex	DEFINITION: “Patient’s physical sex at birth”; PERMISSIBLE VALUES: male, female, other (in any format)	Allows studies of sex-related differences in the disease epidemiology and clinical features
	Patient date of birth	DEFINITION: “Date of patient’s birth recorded in birth certificate, passport or identity card”; FORMAT: complete date (year, month, day) in any format	Allows studies of age-related disease features.
		For privacy reasons, depending on the time course of the disease, this data is to be communicated to the platform at the appropriate level of precision (only month and year or complete)
	Patient city of birth	DEFINITION: “Name of city/town/village where the patient was born as it appears on the birth certificate, passport or identity card”; FORMAT: full name of city.	This data may be communicated to the platform only for some specific diseases for studies of health determinants.
		For privacy reasons, this data is to be communicated to the platform with the appropriate level of precision (e.g. mapped to the province, or to postal code). Moreover, it is important that geographical names are mapped to the INSPIRE identifiers [12]. This will enable the link with platforms organized around environmental spatial information, such as environmental pollution databases. This may offer an additional opportunity to indicate the place with an appropriate granularity to comply with privacy needs.
	Patient country of birth	DEFINITION: “Name of country where the patient was born as it appears on the birth certificate, passport or identity card”; FORMAT: full name of country	Increases the discriminatory power of the EU GUID in global registries
	Diagnosis	Multiple coding according to current relevant classification systems is recommended while waiting for a general reference classification of rare diseases	Attribution of a disease to the case
	Patient city of residence	DEFINITION: “Name of city/town where the patient usually lives”; FORMAT: full name of city	Attribution of the case to a geographic area; prevalence, incidence, mobility
		For privacy reasons, this data is to be communicated to the platform with the appropriate level of precision (e.g. mapped to the province, or to postal code). Moreover, it is important that geographical names are mapped to the INSPIRE identifiers [12]. This will enable the link with platforms organized around environmental spatial information, such as environmental pollution databases. This may offer an additional opportunity to indicate the place with an appropriate granularity to comply with privacy needs.
	Patient country of residence	DEFINITION: “Name of country where the patient usually lives”; FORMAT: full name of country	Attribution of the case to a geographic area; prevalence, incidence, mobility
	ID Treatment Centre	Treating Centre Full name/code; contact data are optional to improve identification	Attribution of the case to the treating setting
	Treating Centre City-Town	FORMAT: full name of city	Attribution of the centre to a geographic area; patient mobility for treatment; planning research/clinical trials
		It is important that geographical names are mapped to the INSPIRE identifiers [12].
	Current and past participation in clinical trials	Yes/No	Planning research/clinical trials
	Patient willingness to be contacted to participate in a future clinical trial	Yes/No	Planning research/clinical trials
	Patient willingness to be contacted about donating biological samples	Yes/No	Planning research/clinical trials
	Patient consent	based on graduated consent forms
	Patient contact	contact details; preferred means of contact (including via intermediary physician); language
Domain 2) Determinants and services
Case characterization	Other cases in the family	Yes/No (If Yes: degree of kinship)	Socio-economic burden of disease
	Healthy carriers in the family	Yes/No (If Yes: degree of kinship)
	Case parents are consanguineous	Yes/no	Contribution of consanguinity
	Genetic features of the patient	Gene-HGNC Gene Symbol	Link to genetic research platforms; patient cohort selection
		Chromosome number
		Nucleotide sequence analyzed and reference sequence systems with accession and version number
		Variant description in HGVS format
		Variant description in other formats
History of diagnosis	Date of first symptoms onset	DEFINITION: “Date when patient first began experiencing symptoms or signs of the rare disease”; FORMAT: complete date (year, month, day) in any format	Age at onset; time to diagnosis
	Date of first contact of patient with the public Health Service	Date of the first time the patient requested a medical visit of the health service with reference to the symptoms of the diagnosed rare disease	Time to diagnosis
	ID Centre/physician referring the patient to the RD centre	Centre/Physician Full name/code; contact data are optional to improve identification	Integration of RD centres in the general Health Service
	Date of current diagnosis	DEFINITION: “Date when the current rare disease diagnosis was made” FORMAT: complete date (year, month, day) in any format	Time to diagnosis; life expectancy at diagnosis
	Status of current diagnosis	Suspected-confirmed	Diagnostic patterns; time to diagnosis; life expectancy at diagnosis
	Methods used for current diagnosis	List to be defined	Diagnostic patterns
	ID Centre which made diagnosis	Centre Full name/code; contact data are optional to improve identification
	Centre which made diagnosis City-Town	FORMAT: full name of city	Patient migration for diagnosis
		It is important that geographical names are mapped to the INSPIRE identifiers [12].
	Patient referred after positive neonatal screening result	Yes/no	Sensitivity of neonatal screening tests; effectiveness of neonatal screening program
Treatments and services	Current orphan drug treatment	DEFINITION: “A list of all current orphan drugs that a patient is currently taking”; FORMAT: name of all active ingredients (ORPHANET list)
	Current off-label drug treatment	DEFINITION: “A list of all current drugs (different from orphan drugs) that a patient is currently taking”; FORMAT: name of active ingredients
	Current drug treatment	DEFINITION: “A list of all current drugs (different from orphan drugs) that a patient is currently taking”; FORMAT: name of active ingredients
	Hospitalizations	DEFINITION: “Cumulative number of patient’s admissions to the hospital due to the rare disease”; FORMAT: number
	Transplantations	Yes/No (If yes: date of transplantation; tranplant material)
	Surgeries	Yes/No (If yes: date of surgery; ID code of Surgery)
	Current dietary regimens prescribed as treatment	Yes/No (If yes: type of regimen)
	Current assistive devices	Yes/No (If Yes: Type of assistive devices used by patient; ID Code of type of device.
	Other treatments	If Yes: Type/Code of treatment; indicate if current or date of administration
	Biomaterial donated	(Yes/no); If Yes: list to be defined (e.g. Tissue or body fluid or other specifications)	Planning research/clinical trials
	ID Biobank where the biological sample is stored up	Biobank Full name/code; contact data are optional to improve identification	Link to Biobanks; planning research/clinical trials
	(if the biobank storing the sample is not known) ID Centre which sampled the biomaterial	Sampling Centre Full name/code; contact data are optional to improve identification of the centre	Link to Biobanks; planning research/clinical trials
Domain 3) Outcomes
	Patient vital status (and date of death)	Live/Dead (If Dead: complete date of death (year, month, day) in any format Required Sources: National Death Registry or National Population Registry
	Education level	Values from 0 to 8, based on the ISCED 2011 classification	Studies of socio-economic burden. Comparison and matching of patient populations from different data sources on the basis of socio-economic data. Applicable to individuals from early childhood.
	Occupational status	Self-defined current economic status (PL031 EU-SILC Target Variable): 11 possible values. (http://epp.eurostat.ec.europa.eu/portal/page/portal/income_social_inclusion_living_conditions/documents/tab/Tab/Personal%20data%20-%20labour.pdf)	Studies of socio-economic burden. Comparison and matching of patient populations from different data sources on the basis of socio-economic data.
			Applicable to individuals more than 16 year old.
	Patient HRQoL index score	Patient health-related quality of life (HRQoL) generic questionnaires with calculation of QALYs or the utility score	assessment of the Health-related Quality of Life; QALYs; equitable decision-making
	Comorbidity	DEFINITION: “Other diseases observed in the patient”; FORMAT: ICD10 (multiple coding in case that other RD are observed)
	Remarkable or unusual symptoms	Remarkable or unusual symptoms, including adverse effects of treatments, and their severity (based on a 5-degree scale).