Table 1 The EPIRARE set of common data elements for the European RDR platform

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).