D4 Review of the State-of-the-art

WORK PACKAGE

WP4

DOCUMENT NAME

PARENT Review of the state-of-the-

art

DOCUMENT VERSION

3.0

DATE 17/07/2013

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Project Title Cross-border Patient

Registries Initiative

Project Acronym PARENT

PARENT Coordinator Matic Meglič, IVZ

Work Package Leader

Authors

Ivan Pristaš

Ivan Pristaš

Vanja Pajić

Mario Šekerija

Vanesa Benković

Tamara Poljičanin

Ranko Stevanović

Tomislav Benjak

Work Package 4

Deliverable 4

Title Review of the State-of-the-

art

Version 3.0

Dissemination Level Public

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Change History

Version Date Status Changes Author Details

1.0 07/12/2012

Major changes in content, a lot more info was added on technical details of registries and such topics were covered as metadata, ISO standards

on metadata, interoperability norms and practices

Vanja Pajić, Ivan Pristaš, Vanesa Benković, Matic

Meglič, Persephone Doupi

Presented at Brussels ExCo meeting and later sent for ExCo

review

2.0 31/05/13

No major changes were made except in Search Methodology description. Inputs from various

stakeholders regarding best practice details and corrections to technical information.

Vanja Pajić, Ivan Pristaš, Vanesa Benković, Mario

Šekerija, Dipak Karla, Persephone Doupi, Arto Vuori, Matic

Meglič, Lidia Di

Minco, Simona Giampaoli, Barbara

Foley, Zane Baltane, Antonio Migliore, Oscar

Zurriaga,

Presented at Brussels ExCo meeting and later sent for ExCo

review

3.0 20/06/13 No major changes were made. Final inputs from

ExCo members on style and content.

Vanja Pajić, Hugo Agius Muscat, Oscar

Zurriaga

Final version was compiled

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INTRODUCTION 5

Needs 5

Activities 5

Problems 5 PATIENT REGISTRIES 6

Registries in general 6

Patient/population/population based/hospital registries 6 EXAMPLES OF PATIENT REGISTRIES USE 8

TYPES OF REGISTRY DATA 10 DATA INTEROPERABILITY 10

INTEROPERABILITY DEFINITIONS 11

SYNTACTIC INTEROPERABILITY 11

SEMANTIC INTEROPERABILITY 11 METADATA 11

METADATA DEFINITIONS 12

METADATA TYPES 12

METADATA STANDARDS 12

METADATA IN HEALTHCARE 16

HEALTHCARE INTEROPERABILITY STANDARDS 16

METADATA REGISTRY 17

METADATA REPOSITORY VS. METADATA REGISTRY 17

COMMON CHARACTERISTICS OF A TYPICAL METADATA REGISTRY 17 RELATED REGISTRIES/PROJECTS/BEST PRACTICES- INTERNATIONAL LEVEL 18

METeOR 18

AHRQ ROPR 19

caDSR 20

NAACCR 20

CORRONA 21

REACH 21

ICHOM 21

CRE-PS 22

ISPOR 23

WHO ICTRP 23 OTHER EXAMPLES OF INTEROPERABILITY PRACTICES WITH POTENTIALLY APPLICABLE ELEMENTS 24

IHE 24

PHDSC 25

i2b2 25 RELATED REGISTRIES/PROJECTS/BEST PRACTICES- EU LEVEL 25

EUBIROD 26

EUROCISS 27

EUReMS 27

EPIRARE 28

EAR EFFORT 27

TREA-MD 29

EuraHS 29

EuroCMR 30

EAACI 21

CICD 21

EGHI 32

ECAB 32

eHGI 33

epSOS 34

EudraGMP 34

EUnetHTA 35

EUDRANET 36

BURQOL-RD 36

HoNCAB 37

HIQA 37

SALUS 38 SEARCH METHODOLOGY 39 Appendix I: Other related metadata Standards and Organizations 46 References 47

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PATIENT REGISTRIES LITERATURE REVIEW

& BEST PRACTICE MAPPING EXERCISE

INTRODUCTION Needs

In light of the Directive on the application of patients' rights in cross-border healthcare (C-B Directive) context of eHealth area, the Cross-border Patient Registries Initiative (PARENT) Joint Action has the aim to rationalize the development and governance of patient registries, thus enabling and promoting effective secondary data use for public health and research purposes. With these aims, one of the goals is to support Member States (MS) in developing comparable and coherent patient registries in fields where this need has been identified (e.g. chronic diseases, rare diseases and medical devices, interventions). In this project a Registry of Registries (RoR) is to be established as a pilot of listings of available registries on an EU level. A metadata repository will be created enabling storage and catalogues of information models, having a comprehensive database shared among registries with options for direct queries in a given registry. In an array of differences among current registries the PARENT JA will aim to address these differences, sharing best practices and tools to support establishment and operation of registries in MS. Activities

In this undertaking, a literature review has been performed, to identify present differences, semantics variety and to serve as knowledge platform for producing the pilot RoR. Also, secondary goals of literature review were to obtain data on benchmarking, models of work, interoperability and valuable information for the designation of the pilot Registry of Registries. Since the preliminary findings discovered lack of country-specific information, the review included sources that would discover references that also include valuable experiences from other projects, such as PARENT’s Associated Projects and other international projects as sources of information not limed to classic peer-reviewed sources. The PARENT RoR is envisioned as a web-accessible service for Patient Registry (and other personal longitudinal data record) holders and interested stakeholders allowing:

Assessment of a particular Patient Registry with the focus on their capacity to exchange data across organizations, borders.

Access to structured information about patient registries in EU space

Search of Registries based on a set of search criteria, comparison of registries based on key metadata such as use of particular standards, clinical field of use, data availability, etc.

The service would be freely/publicly available on the internet at all times to any interested party (registry holders, professional and general public, government employees, researchers and academia, etc.). The service would be in the form of a website. It would have a mechanism to allow setting up accounts, adding new registry listings or updating existing registry listings.

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Problems

The current European registry landscape is often viewed as a collection of divergent registries. Design, development, and maintenance of patient registries revolve around registry platforms (software tools for managing registries’ data). This approach leads to creation of segregated silos, resulting in expensive and inflexible IT systems. Often, registries are built for a single purpose (further explained in the PARENT “10Q” document), with its own data stores and for limited user profiles. Furthermore, registries have different legislative and governance rules and obligations and are spread across different European countries and types of organizations. As a result, patient registries implement only a subset of the registry functions, using and producing only a subset of the registry data, and often not applying existing interoperability approaches (standards, best practices). Thus these registries manifest themselves as islands of data and governance rules. The approach to reducing barriers towards identifying relevant registries as sources of data and exchanging their data across organizations and borders for research and public health purpose lies on following aims: (1) to share the information on individual patient registries; (2) to enable registry holders to benchmark/analyze/assess their registries’ readiness for data exchange in a cross-border and cross-organizational context; (3) to enable interested stakeholders (academia & research, industry, government) to search and identify these sources of data.

PATIENT REGISTRIES Registries in general

A registry is an administrative register (data directory) maintained to store records on all objects to be administered; the administrative process requires that it is possible to identify all objects1. The following definition is valid for both administrative and statistical registries: A register aims to be a complete list of the objects in a specific group of objects or population. However, data on some objects can be missing due to quality deficiencies. Data on an object's identity should be available so that the register can be updated and expanded with new variable values for each object. Complete listing and known identities are thus the important characteristics of a register. 2 A statistical register is based on data from administrative registries that have been processed to suit statistical purposes. The register processing which transforms administrative data into statistical registries gives rise to important methodological questions.3 Terminology in relation to disease registries and clinical databases can be confusing. For example, the terms register and registry are often used interchangeably. The registry is the organization and process that supports a register and should be distinguished from the register itself. One registry may support a number of individual registers.

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Patient/population/population based/hospital registries

Generic experience of running registries may be more important than specific knowledge of the topic when setting up a new register. For example, the expertise of the Danish Tuberculosis Index was used to run registries for ischemic heart disease and stroke. In epidemiology the term register is applied to the file of data concerning all cases of a particular disease or other health-relevant condition in a defined population such that the cases can be related to a population base if the cases are regularly followed up; information on remission, exacerbation, prevalence, case fatality and survival can also be obtained. A register requires that a permanent record be established, including identifying data. Cases may be followed up, and statistical tabulations may be prepared both on frequency and on survival. In addition, the persons listed on a register may be subjects of special studies.4 A characteristic of a register is the validation of cases: a register is not only a list of persons (or events) collected in a systematic way, it is a collection of validated events, defined following standardized diagnostic criteria. A “population registry” is a registry that intends to cover all residents in a given geographic area within a given time period. The coverage of the specific registry may, however, be incomplete, but it is nevertheless a population registry if the aim is to include all the individuals in the target population. A population is defined by geographical boundaries, but usually only residents (or citizens) within a given time period are included in the definition5. The term “population-based registry” should be used when all with a given trait, exposure or event, are intended to be included in the registry. If all hospital admissions in the population are candidates for registration the hospital registry is, in principle, population-based. If the registry only covers insured patients, it is not a population-based disease registry. A registry of hospitalized spontaneous abortions is, on the other hand, population-based, even though far from all spontaneous abortions lead to hospitalization. In this case, the registry is population-based for hospitalized cases. A birth registry is population-based if all births from a given time period are included. If the registry includes all in the population (even the oldest), it becomes a population registry. Intention rather than performance defines the terms. A population-based disease registry aims at including all with the disease in the population, be it self-reported, clinically diagnosed or detected at screening. Population and population-based registries may be further classified as good or bad quality depending on coverage or other characteristics.6 A population-based register includes all cases in a defined population, whether treated at home or in hospital, in whichever season of the year or time of the day they may occur, and would also include rapidly fatal cases unable to reach the medical service (i.e. coronary events: case fatality out of hospital is different in the different countries, depending on primary prevention, time to recovery, etc.). It is crucial to monitor the occurrence of the disease, to understand the changes in the natural disease dynamics, to assess the relations between disease incidence, case fatality and mortality, to monitor the consequences of disease in the community in terms of drugs prescriptions and rehabilitation, the utilization of new diagnostic tools, treatments and their impact. For some diseases which occur suddenly it would be useful consider population-based registers. Hospital-based registers provide number of hospitalizations but do not provide data on less severe events or more severe events and out-of-hospital mortality; hence they cannot

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directly be used to estimate incidence or prevalence in a defined population. Even so, case series from hospital-based registers present important clinical information, in particular detailed information on diagnostic and therapeutic procedures and on risk factor level prior to admission to hospital (length of stay, in-hospital treatment and outcomes). A general, and to PARENT JA the most appropriate, definition of patient registry is that of the Agency for Healthcare Research and Quality (AHRQ - Registries for evaluating patient outcomes: a users’ guide): “an organized system that uses observational study methods to collect uniform data (clinical or other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves a predetermined scientific, clinical, or policy purpose(s)”7. The term registry is defined both as the act of recording or registering and as the record or entry itself. Therefore, “registries” can refer to both programs that collect and store data and the records that are so created. The US National Committee on Vital and Health Statistics describes registries used for a broad range of purposes in public health and medicine as “an organized system for the collection, storage, retrieval, analysis, and dissemination of information on individual persons who have either a particular disease, a condition (e.g., a risk factor) that predisposes [them] to the occurrence of a health-related event, or prior exposure to substances (or circumstances) known or suspected to cause adverse health effects.” Other terms also used to refer to patient registries include clinical registries, clinical data registries, disease registries, and outcomes registries.8

EXAMPLES OF PATIENT REGISTRIES USE The term patient registry is generally used to distinguish registries focused on health information from other record sets. Although PARENT may find the registry definition stated before as the most appropriate for the initiative purposes, there is still no consistent definition in current use. E. M. Brooke, in a 1974 publication of the World Health Organization, further delineated registries in health information systems as “a file of documents containing uniform information about individual persons, collected in a systematic and comprehensive way, in order to serve a predetermined purpose.”9 As the AHRQ guide indicates, registries should be designed and evaluated with respect to their intended purpose(s) which can be broadly described in terms of patient outcomes. Some of major purposes for establishing and running a patient registry describe the natural history of disease, determine clinical and/or cost-effectiveness, assess safety or harm, and measure or improving quality of care, as well as public health surveillance and disease control. There is an extensive body of literature of experience with cancer and other disease surveillance registries available.10 The registries that aim to describe the natural course of disease are usually focused on rare diseases; examples include the international registries for: Niemann-Pick disease11, Fabry disease12 and organic acidurias and urea cycle defects13. Their aim is to contribute to better understanding of natural history of rare diseases through pooling cases of rare diseases, usually multi-nationally and/or across the continents, and studying their outcomes.

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Registries that focus on clinical trials and/or cost-effectiveness are developed on a notion that results from clinical trials cannot routinely be translated into everyday practice. In this manner many studies report disparities between clinical trial results and routine everyday practice1415. Moreover, there is an array of disparities between strict inclusion/exclusion criteria of clinical trials and everyday practice, especially when observing different countries, as well as administering therapy in wider population, than those in the trial. Another two important reasons for the importance of clinical effectiveness registries are the fact that many clinical trials tend to over-recruit patients that are younger than 65 (while in reality, majority of patients with chronic disease are older),16 and that these registries can follow the patients for a much longer period of time than the expensive clinical trials. The cost-effectiveness registries compare costs with clinical outcomes measured in life expectancy units, period free of disease or another clinical outcome, while cost-utility studies compare costs with outcomes adjusted for quality of life (such as QALYs) and thus allow comparisons to be made across conditions given that the measurements are not disease-specific. Perhaps the most well-known example of cost-effectiveness registry, though not a patient registry, is the Tufts Medical Center Cost-Effectiveness (CEA) Registry,17 which is a comprehensive database of 3,190 cost-utility analyses on a wide variety of diseases and treatments. Registries that aim to assess safety or harm associated with the use of various products (drugs) or devices need to anticipate the need for adverse event (AE) detection, processing, and reporting and registry sponsors are encouraged to discuss plans for AE collection and processing with local health authorities when planning a registry. Medical devices are significantly different from pharmaceuticals in the manner in which AEs and product problems present themselves, in the aetiology of their occurrence, and in the regulation governing the defining and reporting of these occurrences, as well as post approval study requirements. Other sources provide more information about defining and reporting of device-related AEs and product problems, and about post marketing studies (including those involving registries).18 When considering the advantages of the safety/harm registries in comparison with spontaneous reporting of adverse events there are two main characteristics of these registries that are extremely important. Firstly, we know from other science fields that any choice data architecture that demands an active and non-systematic effort by the clinician to report an adverse event is inferior (in terms of under-reporting, rather than the quality of reporting) to a systematic follow-up of those events. Secondly, and related to this, in a non-systematic reporting of adverse events we usually do not know the denominator (the exposed population) and are therefore not able to provide any epidemiological measures of disease occurrence. In a structured safety/harm registry with a defined population we can calculate the incidence of adverse events and these registries are becoming increasingly more common in the area of medical products and devices. Finally, registries may be created in order to measure and improve the quality of care, defined as “the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge”. This kind of registry usually compares patients or, sometimes, providers based on the provided treatments or achieved outcomes in relation to performance measures with “gold standards” or some other benchmarks for specific health outcomes (e.g. infection rates). These registries may identify disparities in the availability of care as well as demonstrate potential improvement opportunities.4

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Describing the purpose and the scope of the patient registry a priori is extremely important for the design and future interoperability of the registry. There is a need for different types of data depending on the necessary outputs from the registry itself. For example, if we are attempting only to give a descriptive overview of certain events in a population, we would employ less methodological rigour than if we were trying to answer a specific, focused clinical or public health question. Furthermore, different modes of data collection apply if the focus of the registry is describing the natural history of the disease or if we are attempting to use the knowledge gained in order to improve patient's quality of care. Of course, while each of mentioned purposes may be the starting point of the registry, in the end many registries will be developed to serve more than one purpose.

Analysis and interpretation of registry data

Analysis and interpretation of registry data begin with a series of core questions:

Study purpose: Were the objectives/hypotheses predefined or post hoc?

Patient population: Who was studied?

Definition of event: Which diagnostic criteria were used to define an event

Data quality: How were the data collected, reviewed, and verified?

Data completeness: How were missing data handled?

Data analysis: How were the analyses chosen and performed? While the scientific opportunities that may result from using data from a well-designed registry are clear, there are inherent challenges to making appropriate inferences. A principal concern with registries is that of making inferences without regard to the quality of data, since quality standards have not been previously well established or consistently reported. In some registries, comparison groups may be less robustly defined than in more formal observational designs (e.g., cohort, case-control studies).19

Types of registry data

Analysis of a registry should explicitly provide the following information:

Patient: What are the characteristics of the patient population in terms of demographics, such as age, gender, race/ethnicity, insurance status, and clinical and treatment characteristics (e.g., past history of significant medical conditions, disease status at baseline, and prior treatment history)?

Exposure: Exposure could be therapeutic treatment such as medication or surgery; a diagnostic or screening tool; behavioural factors such as alcohol, smoking habits, and diet; or other factors such as genetic predisposition or environmental factors.

Endpoints (or outcomes): Outcomes of interest may encompass effectiveness or comparative effectiveness, the benefits of a health care intervention under real-world circumstances, and safety—the risks or harms that may be associated with an intervention. Examples of effectiveness outcomes include survival, disease recurrence, symptom severity, quality of life, and cost-effectiveness. Safety outcomes may include infection, sensitivity reactions, cancer, organ rejection, and mortality. Endpoints must be precisely defined at the data collection and analysis stages.

Covariates: As with all observational studies, comparative effectiveness research requires careful consideration, collection, and analysis of important confounding and effect modifying variables. For valid analysis of risk or benefit that occurs over a period of time following therapy, detailed accounting for time factors is required.

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For exposures, dates of starting and stopping a treatment or switching therapies should be recorded. For outcomes, the dates when follow-up visits occur and whether or not they lead to a diagnosis of an outcome of interest are required in order to take into account how long and how frequently patients were followed. Dates of diagnosis of outcomes of interest or dates when patients complete a screening tool or survey should be recorded. At the analysis stage, results must also be described in a time-appropriate fashion. Different analytic approaches may be required to address issues of patients enrolling in a registry at different times and/or having different lengths of observation during the study period.20 21

It should be noted here however that the terms with which the registries are described (i.e. population-based registry, clinical registry, rare disease registry, clinical or patient database, survey) can sometimes be misleading due to different country-specific or registry-specific practices, historical conditions, legal and governance structure in place or any other reason specific to the registry. Also, the reasons for establishing a registry can vary and change in time and sometimes the name of the registry may stay when the registry purpose has changed (became more specific or included multiple clinical fields).

DATA INTEROPERABILITY Data interoperability is one of the main goals of PARENT project as interoperability makes available the reuse of healthcare data, for patient care and clinical research, relying on standardized approaches in data representation. European patient and other healthcare registries abound with terminologies and dictionaries supporting the representation of patient and other healthcare data, but these are not necessarily interoperable and one of PARENT project’s main goals is to “scan” the European healthcare data horizon in search of useful interoperability practices and make use of state-of-the-art models for data sharing.22

INTEROPERABILITY DEFINITIONS

Interoperability is the ability of two or more systems or components to exchange information and to use the information that has been exchanged.23 Interoperability means to be able to accomplish end-user applications using different types of computer systems, operating systems, and application software, interconnected by different types of local and wide area networks.24 Achieving data interoperability between organizations relies upon agreed meaning and representation (metadata) of data. For managing and registering metadata, many organizations have built metadata registries (MDRs) in various domains based on international standard for MDR framework, ISO/IEC 11179.25

SYNTACTIC INTEROPERABILITY

If two or more systems are capable of communicating and exchanging data, they are exhibiting syntactic interoperability. Specified data formats, communication protocols and the like are fundamental. XML or SQL standards are among the tools of syntactic interoperability.26

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SEMANTIC INTEROPERABILITY

Beyond the ability of two or more computer systems to exchange information, semantic interoperability is the ability to automatically interpret the information exchanged meaningfully and accurately in order to produce useful results as defined by the end users of both systems. To achieve semantic interoperability, both sides must refer to a common information exchange reference model. The content of the information exchange requests are unambiguously defined: what is sent is the same as what is understood.27 In order to achieve semantic interoperability of healthcare data, it is important not only to specify clinical entries and documents and the structure of data in patient registries, but also to use clinical terminology to describe clinical data. There are three types of clinical terminology: interface terminology to support a user-friendly structured data entry; reference terminology to store, retrieve, and analyze clinical data; and classification to aggregate clinical data for secondary use.28 It has been noted that a semantic metadata mapping procedure is able to maximize the interoperability among metadata. The methodology explored consists of three processes such as identifying metadata element sets, grouping data elements, and mapping semantically.29

METADATA In its most simple definition, metadata is data used to describe other data in order to better understand, categorize and catalogue that data. It provides information about a data element's attributes and values. Metadata consist of “statements” about data, where each statement consists of an element ("attribute" or "relationship") of the entity, and a "value" for that element30. Healthcare metadata describes healthcare data information according to a predetermined set of value sets. Metadata interoperability in healthcare can be described as a measure of the compatibility of two health-related metadata value sets.31 In order for a healthcare registry to achieve interoperability with other data sources (medical or other), metadata sets need to be compatible (i.e. syntactically and semantically). Metadata are used to provide answers to the “who, what, where and when” of data contained in an information system (i.e. patient registry) and can be considered from the perspective of both the healthcare data producer (patient registry owner or registry holder) and the healthcare data consumer (second party, which uses data for secondary purposes). For the registry data producer, healthcare metadata are used to document registry data in order to inform data users of their characteristics while for the data consumer, registry metadata are used to both discover data and assess their appropriateness for particular healthcare needs.

METADATA DEFINITIONS

As has previously been said, metadata is often defined as data about data.32 33 34 35 Metadata is structured information that describes, explains, locates, or otherwise makes it

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easier to retrieve, use or manage an information resource, especially in a distributed network environment such is a patient registry.36 Structural metadata is usually considered to be data about the containers of data and is opposed to content about individual instances of data content or meta-content, the type of data usually found in library catalogues37. Both kinds of metadata are used in patient registries, depending on the registry purposes and data architecture.38

METADATA TYPES

Healthcare metadata found in patient registries is usually categorized into three types:

Descriptive healthcare metadata describes an information resource for identification and retrieval through elements such as patient name, patient ID, and diagnosis.39

Structural metadata documents relationships within and among objects through elements such as links to other components (how patient’s name and ID relates to a more complex clinical picture).40

Administrative metadata helps to manage information resources through elements such as patient case number, hospitalization dates, and other technical information for purposes of patient management.41

Metadata is defined as data providing information about one or more aspects of the data, such as:

Means of creation of the registry data

Purpose of the registry data

Time and date of registry data creation

Creator or author of registry data

Location on the organization’s computer network where the registry data was created

Metadata standards used Registry metadata are usually made available in two modes of data completeness. Discovery mode of metadata typically provides a minimum of information for enabling the data user to find out if a particular dataset exists, provide information on data location and data ownership links to other relevant information on the data. Full metadata mode includes information on other aspects of data usage such as data quality and also technical details for data access and purposeful usage. Metadata can be stored and managed in a database, often called a metadata registry or Metadata repository.42

METADATA STANDARDS

In order to support empirical medical research concerning reuse and improvement of the expressiveness of study data and hence promote syntactic as well as semantic interoperability, metadata standards are required for the maintenance and re-usage of data element collections.43 For each data element defined, a metadata standard provides rules for how data should be included, representation rules for data and allowable data values.44 To harvest information from a set of metadata it is necessary to understand the schema of the metadata.45

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Metadata registries are considered to be a solution to the problem of data sharing and standardizing of information on the Internet. A standardized approach to this problem came in the form of ISO/IEC 11179 Information Technology Standard for Specification and Standardization of Data Elements.46 Metadata standards are international standards that apply to metadata. Much work is being accomplished in the national and international standards communities, especially ANSI (American National Standards Institute) and ISO (International Organization for Standardization) to reach consensus on standardizing metadata and registries. They are the requirements which are intended to establish a common understanding of the meaning or semantics of the data, to ensure correct and proper use and interpretation of the data by its owners and users. To achieve this common understanding, a number of characteristics, or attributes of the data have to be defined, also known as metadata.47 The core ISO metadata standard is ISO/IEC 11179. All metadata standards are a set of vocabulary terms which can be used to describe resources for the purposes of metadata discovery. One of the widely used metadata standard sets is the Dublin Core Metadata Element Set48 which is used in the following metadata standards: IETF RFC 501349, ISO Standard 15836-200950, NISO Standard Z39.8551, Microformats (not a standard in itself but is a web based approach to semantic interoperability using HTML and XHTML).52 ISO/IEC 24744 Software Engineering — Meta-model for Development Methodologies is an ISO standard for software engineering meta-modelling for development methodologies. The aim of SEMDM is to define methodologies in information-based domains, i.e. areas characterized by their intensive reliance on information management and processing, such as software, business or systems engineering. The SEMDM combines key advantages of other meta-modelling approaches with none of their known drawbacks, allowing the seamless integration of process, modelling and people aspects of methodologies.53 ISO/IEC 11179 (formally known as the ISO/IEC 11179 Metadata Registry (MDR) standard) is an international standard for representing metadata for an organization in a metadata registry. ISO/IEC 11179-3:2013 specifies the structure of a metadata registry in the form of a conceptual data model. While the model diagrams are presented in UML notation, ISO/IEC 11179-3:2013 does not assume nor endorse any specific system environment, database management system, database design paradigm, system development methodology, data definition language, command language, system interface, user interface, computing platform, or any technology required for implementation. ISO/IEC 11179-3:2013 does not directly apply to the actual use of data in communications and information processing systems. ISO/IEC 11179-3:2013 specifies basic attributes which are required to describe metadata items, and which might be used in situations where a complete metadata registry is not appropriate (e.g. in the specification of other International Standards).54 NISO Z39.85 Standard is a metadata elements standard used for resource description in a cross-disciplinary information environment.55 Microformats are extensions to HTML for marking up various types of data. Dublin Core uses microformats to publish a standard API that is consumed and used by search

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engines, browsers, and other IT tools. They are sets of simple, open data formats built upon existing and widely adopted standards.56 Below is a catalogue of other notable metadata projects, organizations and public documents which use data to describe other data in a systematic and standardized manner in order to achieve interoperability between disparate information systems. Some of them are health-related and others are used across knowledge domains in for interoperability purposes of various kinds.

CCD: Continuity of Care Document (http://www.hl7.org/implement/standards/product_brief.cfm?product_id=6)

CCHIT: Certification Commission for Health Information Technology (https://www.cchit.org/)

CCR: Continuity of Care Record (http://www.astm.org/Standards/E2369.htm)

CDA: Clinical Document Architecture (http://www.cdc.gov/nhsn/CDA/)

CPOE: Computerized Physician/Provider Order Entry (http://www.cpoe.org/)

FIPS: Federal Information Processing Standards (http://www.nist.gov/itl/fips.cfm)

HIPAA: Health Insurance Portability and Accountability Act of 1996 (Title II of HIPAA, known as the Administrative Simplification (AS) provisions, requires the establishment of national standards for electronic health care transactions and national identifiers for providers, health insurance plans, and employers57) (http://www.cms.gov/Regulations-and-Guidance/HIPAA-Administrative-Simplification/HIPAAGenInfo/index.html?redirect=/HIPAAGenInfo/)

HIT: Health Information Technology (http://www.ama-assn.org/ama/pub/physician-resources/health-information-technology.page)

HITECH: Health Information Technology for Economic and Clinical Health (http://www.hhs.gov/ocr/privacy/hipaa/administrative/enforcementrule/hitechenforcementifr.html)

HITSP: Healthcare Information Technology Standards Panel (http://www.hitsp.org/)

HL7: Health Level Seven (http://www.hl7.org)

ICD: International Classification of Diseases (http://www.who.int/classifications/icd/en/)

o ICD–9–CM International Classification of Diseases, 9th Revision, Clinical Modification (http://www.cdc.gov/nchs/icd/icd9cm.htm)

o ICD–10–PCS International Classification of Diseases, 10th Revision, Procedure Coding System (http://www.cdc.gov/nchs/icd/icd10cm.htm)

o ICD–10–CM International Classification of Diseases, 10th Revision, Clinical Modification (http://www.cdc.gov/nchs/icd/icd10cm.htm)

LOINC: Logical Observation Identifiers Names and Codes (http://loinc.org/)

NCPDP: National Council for Prescription Drug Programs (www.ncpdp.org )

ONC: Office of the National Coordinator for Health Information Technology (provides certifications for EHRs) (http://oncchpl.force.com/ehrcert)

PHII: Population Health Impact Institute (http://www.phiinstitute.org/)

PHDSC: Public Health Data Standards Consortium (http://www.phdsc.org/)

PQRI: Physician Quality Reporting Initiative (http://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/PQRS/index.html?redirect=/PQRS/)

REST: Representational state transfer (http://www.ics.uci.edu/~fielding/pubs/dissertation/top.htm)

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SNOMED–CT: Systematized Nomenclature of Medicine Clinical Terms (http://www.ihtsdo.org/)

SOA: Service Oriented Architecture (http://www-01.ibm.com/software/solutions/soa/)

SOAP: Simple Object Access Protocol (http://www.w3.org/TR/soap/)

UCUM: Unified Code for Units of Measure (http://unitsofmeasure.org/trac/)

UMLS: Unified Medical Language System (http://www.nlm.nih.gov/research/umls/)

XML: eXtensible Markup Language (http://www.w3.org/XML/)

W3C: World Wide Web Consortium (http://www.w3.org/) Adherence to metadata standards is essential to ensure registry interoperability, especially in a European network of healthcare data users and publishers. Both the patient registry data publishers and data users are not supposed to know the technical detail of these metadata standards. One of PARENT project's roles is to provide the guidelines, best practices, methodologies and IT tools to ensure standard compliance to metadata standards while providing an intuitive GUIs that would allow registry owners (i.e. data providers) and data users to focus on the content instead of its underlying technical structure. To conclude, metadata standards are requirements which are intended to establish a common understanding of the meaning or semantics of the data, to ensure correct and proper use and interpretation of the data by its owners and users. To achieve this common understanding, a number of characteristics, or attributes of the data have to be defined, also known as metadata24. Other metadata standards are mentioned in the Appendix I of the document. Note: The College of Healthcare Information Management Executives (CHIME) in the USA has recently rejected the idea that metadata standards should be used to support the meaningful use of healthcare and patient data in a US federal patient registry58. "We do not believe enough progress has been made, or evidence gathered, to support the technologies and strategies needed to include metadata standards as part of Meaningful Use Stage 2," wrote Richard Correll, CHIME president and CEO59. This could have implications on the usage of metadata standards on European patient registries as well, as there are no unique standards across the healthcare area.

METADATA IN HEALTHCARE

To integrate the existing large quantity of health data from various sources usually healthcare registries), a couple of interoperable data models were designed to organize data items, avoiding conflicts and duplications in between. For data quality purposes, standardized data elements should be extracted from the data items and defined as attributes of classes in the data model by choosing essential metadata attributes.60 Treating data items as instances of well-defined data elements might make data in different contexts manageable and agreeable. To be interoperable, further methodological work should be performed to standardize detailed medical information, and integrate the approach of metadata harmonization.61 In general, a full review of metadata in healthcare might be quite difficult since healthcare does not take a uniform approach to how metadata is understood (the term itself is not always used). Patient or any other healthcare metadata registries can be developed to support a variety of uses, including public health surveillance, patient care (management of chronic illness), connecting patients with clinical trials, post-

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marketing surveillance for adverse events and research. Each of these purposes has different regulations and stakeholders, and different relevant data standards. While some disease registries are "standardized" and relevant resources are available, there is no standard protocol or set of data collection elements for all registries.62

HEALTHCARE INTEROPERABILITY STANDARDS

Healthcare interoperability standards provide a framework for the exchange, transformation and retrieval of electronic health information covering the complete lifecycle of information sharing between eHealth systems. Two best known and most widely used are Health Level 7 and SNOMED CT. HL7 – Health Level 7 (http://www.hl7.org) HL7 provides standards for interoperability that improve care delivery, optimize workflow, reduce ambiguity and enhance knowledge transfer among all of our stakeholders, including healthcare providers, government agencies, the vendor community, fellow SDOs and patients. In all of our processes we exhibit timeliness, scientific rigor and technical expertise without compromising transparency, accountability, practicality, or our willingness to put the needs of our stakeholders first. "Level Seven" refers to the seventh level of the International Organization for Standardization (ISO) seven-layer communications model for Open Systems Interconnection (OSI) - the application level. The application level interfaces directly to and performs common application services for the application processes. Although other protocols have largely superseded it, the OSI model remains valuable as a place to begin the study of network architecture. SNOMED CT (http://www.ihtsdo.org/snomed-ct) SNOMED CT is a clinical terminology for the electronic health record (EHR) and contains more than 311,000 active concepts with unique meanings and formal logic-based definitions organized into hierarchies. When implemented in software applications, SNOMED CT can be used to represent clinically relevant information consistently, reliably and comprehensively as an integral part of producing electronic health records63.

METADATA REGISTRY

The metadata contained in a metadata registry is used to provide descriptions about the types of data they contain in a centralized manner usually for a predefined registry purpose. The metadata repository is a way to ensure consistency of metadata or metadata quality. The metadata in a metadata registry is stored in a registry database and then referenced on-demand by the applications or web services that need it for various business purposes.

METADATA REPOSITORY VS. METADATA REGISTRY

As both terms are sometimes used interchangeably, some further discussion is in order to explain the differences and similarities between the two. A metadata repository is similar to a metadata registry in that it also only stores metadata (i.e. data explaining registry data). A metadata repository is different from a metadata registry in that a repository provides information on data searching and reporting.64 On the other hand, a metadata registry is a

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protected area where only approved individuals may make changes (those individuals are usually the organization's data architect or data modelling team) and it stores data elements that include both semantics and representation. The semantically interoperable areas of a metadata registry contain the meaning of all the data elements with precise value definitions. The representational areas of a metadata registry define how the data is represented in a specific format such as within a database or a structure file format such as XML. 65 The metadata repository is responsible for physically storing and cataloguing metadata 66. The metadata repository should also be designed so that current and historical metadata can both be accessed.67 Metadata repositories usually store metadata in four broad categories – data ownership, descriptive characteristics of data, data rules and policies, and physical characteristics of the data stored in a system. Data ownership points to the data owner. The descriptive characteristics define the data names and data types. They also define business data or business processes concerning the usage of data. Data rules and policies describe data security issues, data quality and relationships between data. Physical data characteristics define the data source and physical location of data. Like building a logical data model for creating a relational database, a metadata model for a patient registry describes the relation of metadata requirements to business data in a medical or healthcare organization.68

COMMON CHARACTERISTICS OF A TYPICAL METADATA REGISTRY

A metadata registry typically contains the following characteristics:

Data itself

XML files

XML Schemas (Metadata structured in XSD format)

User Interface(s)

Metadata stored in Metadata Repository

Discovery metadata

Web Service Definition Language (WSDL) for interface metadata

Universal Description, Discovery and Integration (UDDI)

Electronic Business Using eXtensible Markup Language (ebXML)

Discovery metadata stored in Catalogs

Follows ISO/IEC 11179 Standards for metadata registries

RELATED REGISTRIES/PROJECTS/BEST PRACTICES – INTERNATIONAL LEVEL For most of these projects the descriptions used are from the project websites. References are provided in the project title. The criteria for recognizing best practices are in accordance with overall PARENT aims, and include projects, organizations, initiatives, registries etc. working on national, regional or international level in the field of:

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- Recognizing and converging similar sources of data (based on disease, device and/or service) in order to improve surveillance, quality, outcomes, safety and/or effectiveness.

- Tackling different levels of data exchange (individual or aggregated level, metadata) between similar (group of registries) or different sources of data (registries – EHR – insurance databases).

- Healthcare data exchange issues such as standards, interoperability, metadata, platform, common datasets etc.

- Defining and addressing needs for efficient health information exchange on different levels (patients, health care providers, researchers, payers, decision makers etc.) and ways to address those.

- Promoting collaboration, reducing redundancies, and improving transparency among patient registry holders.

- Patient registries classification, definitions, taxonomy, purpose, development and governance.

- Adding value through secondary use of health data. METeOR (Metadata Online Registry) (http://meteor.aihw.gov.au ) The METeOR is Australia’s repository for national metadata standards for health, housing and community services statistics and information. It is a Metadata registry based on the 2003 version of the ISO/IEC 11179 Information technology - Metadata registries standard. The registry was developed to store, manage and disseminate metadata in the Australian health, community services and housing assistance sectors. Two types of metadata are used in METeOR - metadata items and navigational items. Metadata items proceed through a series of registration states until they become endorsed as standards by the relevant registration authority. Thus, the metadata items become official data standards. Besides the metadata items, this registry also hold the navigational items. The Navigational items are added to METeOR by the Registrars to make the navigation and management of metadata items easier and more meaningful. This means that navigational items are not official data standards. Two navigational items are currently used in METeOR the Object class specializations and the Property groups.69 AHRQ RoPR (Registry of Patient Registries) (https://patientregistry.ahrq.gov) The Agency for Healthcare Research and Quality (AHRQ) has designed and deployed the RoPR system to complement ClinicalTrials.gov project by providing additional registry-specific data elements. This system contains registry specific information intended to promote collaboration, reduce redundancy, and improve transparency among registry holders. The RoPR data entry system allows for registry owners to provide information about the classification and purpose i.e. the type of registry and its purpose, contact and conditions of access (the circumstances under which the registry can be contacted, and contact information for those interested in collaboration, participation and/or data access), progress reports - includes information about the growth of the registry and any relevant references to available progress reports, common data elements (the descriptions of registry-specific standards, scales, instruments, and measures).The Registry of Patient Registries (RoPR) was launched on December 1, 2012 and is available online at

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https://patientregistry.ahrq.gov. Sponsored by the Agency for Healthcare Research and Quality (AHRQ), the RoPR is a database of existing patient registries that was designed with extensive stakeholder participation to promote collaboration, reduce redundancy, and improve transparency in registry-based research.70 caDSR (https://wiki.nci.nih.gov/display/caDSR) The caDSR (Cancer Data Standards Registry and Repository) is a database and a set of APIs and tools to create, edit, control, deploy, and find common data elements (CDEs) for use by metadata consumers, and information about the UML models and Forms containing CDEs for use in software development. The common data elements are developed by the National Cancer Institute Centre for Biomedical Informatics and Information Technology (NCI CBIIT) and caBIG® partners in the research community, to be used as metadata descriptors for research and caCORE-like applications. The UML models represent information domains and are developed by research partners in collaboration with CBIIT. The semantics of the data elements used in the models are extracted and transformed into administered components in the caDSR database. When a UML model is registered in caDSR, the collection of related CDEs are classified as part of the UML Model and visible as a collection in the UML Model Browser. Use of CDEs addresses a biomedical data management problem, namely the many and varied ways in which similar or identical concepts have been collected and stored in databases. Common information building blocks or "common data elements" are used for capture of data and for reporting, facilitate understanding and sharing of cancer research information. All of the caDSR tools and interfaces connect to the same central database. NCI chose an international standard to represent the CDEs in the database, the ISO/IEC 11179 Standard for Metadata Registries. This somewhat complex standard offers a richly expressive model for metadata that does a good job of supporting the variations needed for biomedical applications. In implementing the ISO/IEC 11179 model, NCI has included extensions, among them two important additional types of content in the caDSR, Forms and UML Model associations. For clinical trials applications, a Form corresponds to a Case Report Form (CRF). CDEs can be grouped together for use in Modules on Case Report Forms (CRF). Modules are grouped together to make a CRF. A Protocol, which corresponds to a clinical trial protocol, is made up of a collection of CRFs. UML Model class associations are recorded as a new kind of administered item, with key semantic attributes of the association stored as an Object Class Relationship. ThecaDSR tools include interactive tools to perform various tasks associated with managing and deploying CDEs, and a series of tools that support reviewing externally generated forms to see if they are CDE-compliant, that is, comprised of approved CDEs found in the caDSR. NAACCR (www.naaccr.org) The North American Association of Central Cancer Registries, Inc. (NAACCR) is a professional organization that develops and promotes uniform data standards for cancer registration; provides education and training; certifies population-based registries; aggregates and publishes data from central cancer registries; and promotes the use of cancer surveillance data and systems for cancer control and epidemiologic research, public health programs, and patient care to reduce the burden of cancer in North America. One of NAACCR’s first goals was to achieve consensus on cancer registration standards among the many standard-setting organizations in the United States and Canada, in order to facilitate compilation and comparison of information across different registries. Today, nearly all registries in North

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America have adopted the NAACCR consensus standards. NAACCR updates these standards annually to meet the changing needs of the registry community. Every year, NAACCR issues a call for data from its registry members. These data are evaluated for accuracy and compiled into analytic files to produce CINA, an annual statistical monograph of cancer incidence in the United States and Canada; CINA+ Online, an online query system of cancer incidence data for the previous five years from selected member registries; and CINA Deluxe, a data file for NAACCR researchers to conduct cancer surveillance systems. NAACCR also collaborates with other cancer organizations to produce the Annual Report to the Nation on the Status of Cancer.71 CORRONA (http://www.corrona.org) The Consortium of Rheumatology Researchers of North America, Inc. (CORRONA) was founded in 2000 by leading rheumatologists dedicated to advancing and improving the care of patients with rheumatic diseases. CORRONA's mission is to advance rheumatology research and improve the quality of rheumatology patient care. CORRONA is an independent registry without any ownership links to the pharmaceutical industry. Data on Rheumatoid Arthritis, Psoriatic Arthritis, Osteoarthritis, Osteoporosis, and Osteoporosis Risk derived from rheumatologists and patients are entered from directly by the physician. The data are entered in an aggregate from throughout the United States and can then be analyzed by members of the CORRONA team. Data from the CORRONA registry can be used to derive insights regarding the effectiveness, and safety of drugs used to treat these diseases. It can also be used for the purposes of improved patient care and quality management. Mission is to provide excellence in the necessary interaction between the Clinicians and the scientific community to gather high quality data and data analysis for the advancement of treatment for the disease. CORRONA and its adaptive database gathering technology are constantly changing to follow the needs of the scientific community to collect, analyze and disseminate expertise in the field of rheumatoid arthritis disease.72 REACH (www.reachregistry.com)* The risk of atherothrombosis is a large health care burden worldwide. With its global prevalence, there is a need to understand all the associated risk factors, both old and new, and their interdependencies in the development of this complex disease leading to myocardial infarction, ischaemic stroke, and vascular death and, thus, the major cause of mortality throughout the world.73The Reduction of Atherothrombosis for Continued Health (REACH) Registry (Australia74) aims at improving the treatment of patients with atherothrombosis or atherothrombotic risk factors. The aim of this study is to report the 3-year medication use and outcomes in symptomatic patients enrolled in the REACH. Outcomes assessed in REACH project are MI/stroke/vascular death and rehospitalisation for vascular events other the MI/stroke/vascular death.75 *Link currently unavailable

ICHOM (http://www.ichom.org) ICHOM is a not-for-profit organization committed to the advancement of value-based health care delivery by facilitating outcomes measurement and benchmarking globally. It offers a differentiated approach to improving health care value measurement by creating an

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international consortium of leaders in academia, clinical practice, patient organizations, and business. Among four strategic priorities one of the most interesting to PARENT is No3: Catalyze the establishment and improvement of disease registries- the Consortium has constructed a strategic framework for positioning registries to best enable value-based care. The Registry Development Compass (RDC) serves as a multidimensional tool to guide registry development along five key areas: Governance and Control, Designing Measures, Collecting Data, Analyzing and Reporting, Driving Change. Registries that have significantly advanced their practices along each of the five compass axes are best positioned to support providers, motivate excellence and promote value-based health care. The RDC offers a guide for the next steps in maximizing clinical impact for a registry at any stage in development. Through the RDC, ICHOM aims to rapidly diffuse outcomes measurement best practices and facilitate a community of registry leaders and stakeholders globally.76 CRE-PS (http://www.med.monash.edu.au/sphpm/creps/) Centre of Research Excellence in Patient Safety (CRE-PS) was established in late 2005 with the objective of developing national research capability and capacity that in turn improve patient safety. CRE-PS designs, conducts, promotes, and promulgates a high quality multi-centre research to improve quality, safety, efficiency and effectiveness of health care for Australians. Research and patient safety initiatives in each state and territory, and internationally has been undertaken. Research has focused on four main areas: the use of data to monitor quality of care, improving information transfer, reducing medication error and patient safety. It was established to design, conduct, promote and promulgate high quality multi-centre research to improve quality, safety, efficiency and effectiveness of health care for Australians. Funding for this national centre was provided by the Australian Council for Safety and Quality in Health Care (now the Australian Commission on Safety and Quality in Health Care) and was awarded through the NMHRC. The consortium includes a team of experts in health care risk management and an advisory group including patient safety specialists from the UK and the US. The objectives of this agreement include the establishment of a national Centre of Research Excellence for Patient Safety that will promote and develop resources to improve patient safety, and with the intention that it will lead to: a better identification of factors that affect patient safety in clinical situations, a better understanding of the role of human performance factors, organizational factors, and system deficiencies in the generation of clinical errors, the more effective use of registry data to identify variations in performance, and the development of research models to investigate them, a better understanding of the role of patients and physicians in working with staff to identify and support innovation, an understanding of error management in other industrial settings and its potential application to health care, the use of clinical simulation to provide a realistic and safe environment for research, training, and education in the recognition and management of error-prone situations, the development of mechanisms for ensuring the uptake and application of research outcomes, and the training of new researchers with an appreciation of the role of multidisciplinary research in studying patient safety. These objectives are consistent with the Council’s overall purposes with regards to patient safety research, which are to strengthen the evidence base for developing and implementing system improvements to reduce the occurrence of adverse events, and to continually improve the safety and quality of care for patients in Australia.77

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ISPOR (https://www.ispor.org) The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) promotes the science of pharmacoeconomics (health economics) and outcomes research (the scientific discipline that evaluates the effect of health care interventions on patient well-being including clinical, economic, and patient-centred outcomes) and facilitates the translation of this research into useful information for healthcare decision-makers to increase the efficiency, effectiveness, and fairness of health care to improve health. Founded in 1995, ISPOR is a non-profit public organization for educational and scientific purposes, as defined by the United States Internal Revenue Service, and a non-profit research organization under the European Commission 7th Framework Program. ISPOR has over 6500 members from 100 countries. In addition, each of the 62 ISPOR Regional Chapters have more than 4800 members, extending ISPOR outreach to over 11,300 members. ISPOR provides and promotes quality education on good outcomes research practices as well as health policy issues on topics such as modelling, economic evaluation, patient-reported outcomes (quality of life), clinical observational or retrospective study research methods, and use of outcomes research in health care decisions. ISPOR promotes research by providing tools for health care researchers and health care decision makers. Tools include 44 ISPOR Good Outcomes Research Practice Reports (consensus documents on key outcomes research methods; over 125,000 article downloads in past 12 months), ISPOR Research Digest (searchable database of 20,000 abstracts with over 8,000 presentation PDFs from ISPOR meetings), Pharmacoeconomic (PE) Guidelines Around the World (comparison of PE Guidelines from different countries), the Global Health Care Systems Road Map (description of health care and reimbursement systems around the world), and more – all freely available at the ISPOR website. ISPOR provides and promotes communication through the ISPOR meetings, Value in Health (ISPOR’s peer-reviewed scientific journal), Value in Health Regional Issues (ISPOR’s peer-reviewed scientific journal focusing on Asia, Latin America, Central / Eastern Europe, Western Asia, and Africa) and, ISPOR CONNECTIONS (ISPOR technical and news journal). ISPOR Task Forces and Special Interest Groups facilitate and encourage the interchange of expert knowledge and communications among the research community, health care professionals, practitioners, decision-makers, manufacturers, payers, policy makers and educators around the globe. ISPOR’s core operations are funded by membership fees, meeting registration fees and event sponsorship. Meeting content, including contributed issue panels, workshops, and research and plenary sessions are determined by independent evaluators selected from the diverse membership of the Society.78 WHO ICTRP (www.who.int/ictrp) The mission of the WHO International Clinical Trials Registry Platform is to ensure that a complete view of research is accessible to all those involved in health care decision making. This should improve research transparency and ultimately strengthen the validity and value of the scientific evidence base. Following the Ministerial Summit on Health Research that took place in Mexico City, Mexico, in November 2004, participants called for the WHO to facilitate the establishment of “a network of international clinical trials registries to ensure a single point of access and the unambiguous identification of trials”. This was further expanded on during the 58th World Health Assembly in Resolution WHA58.34 that called on the global scientific community, international partners, the private sector, civil society, and other relevant stakeholders to: “establish a voluntary platform to link clinical trials registries

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in order to ensure a single point of access and the unambiguous identification of trials with a view to enhancing access to information by patients, families, patient groups and others”. These details are published on a publicly-accessible website managed by a registry conforming to WHO standards. The main aim of the WHO ICTRP is to facilitate the prospective registration of the WHO Trial Registration Data Set on all clinical trials, and the public accessibility of that information.79

OTHER EXAMPLES OF INTEROPERABILITY PRACTICES WITH POTENTIALLY APPLICABLE ELEMENTS IHE (www.ihe.net) Integrating the Healthcare Enterprise (IHE) brings together users and developers of healthcare information technology (HIT) in an annually recurring process: Clinical and technical experts define critical use cases for information sharing, technical experts create detailed specifications for communication among systems to address these use cases, selecting and optimizing established standards, industry implements these specifications called IHE Profiles in HIT systems. IHE tests vendors’ systems at carefully planned and supervised events called Connectathons. IHE also organizes demonstrations of IHE-compliant systems working in real-world clinical scenarios at medical meetings and other venues. IHE committees follow the four-step annual process to address interoperability in a variety of clinical domains: anatomic pathology, eye care, IT infrastructure, laboratory, patient care coordination, patient care devices, quality, research and public health, radiation oncology and radiology. Healthcare professionals seeking to acquire or upgrade systems need a convenient, reliable way of specifying a level of compliance to standards sufficient to achieve truly efficient interoperability. The purpose of the IHE initiative is to meet that need. IHE is organized across a growing number of clinical and operational domains. Each domain produces its own set of Technical Framework documents, in close coordination with other IHE domains. Committees in each domain review and republish these documents annually, often expanding with supplements that define new profiles. Initially each profile is published for public comment. After the comments received are addressed, the revised profile is republished for trial implementation: that is, for use in the IHE implementation testing process. If criteria for successful testing are achieved, the profile is published as final text and incorporated. IHE is organized by clinical and operational domains. In each domain users with clinical and operational experience identify integration and information sharing priorities and vendors of relevant information systems develop consensus, standards-based solutions to address them. Each domain includes a technical committee, whose primary task is developing and documenting this solutions (known as integration profiles), and a planning committee, whose primary tasks are long-term scope planning and organizing deployment activities (such as testing events and educational programs). Each domain develops and maintains its own set of Technical Framework documents. Coordination among domains is the responsibility of the Domain Co-chairs Committee, comprising representatives from each of the domain planning and technical committees. IHE Profiles organize and leverage the integration capabilities that can be achieved by coordinated implementation of communication standards, such as DICOM, HL7, W3C and security standards. They provide precise definitions of how standards can be implemented to meet specific clinical needs.80

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PHDSC (www.phdsc.org) The Public Health Data Standards Consortium (PHDSC) is a US national non-profit membership-based organization of federal, state, and local health agencies; professional associations, academia; public and private sector organizations; international members; and individuals. Its goal is to empower the healthcare and public health communities with health information technology standards to improve individual and community health. The Consortium is committed to bringing a common voice from the public health community to the national efforts of standardization of health information for healthcare and population health. To fulfil this commitment the Consortium identifies priorities for the new national standards for population health and promotes the integration of health-related data systems to meet the health data needs of public and private organizations, agencies and individuals. They also participate in national and international efforts on the standardization of health-related information, represent public health interests in standards development organizations, data content committees & standards harmonization entities and educate the public health community about health information technology standards and the health information technology community about public health. PHDSC's goal is to empower the healthcare and public health communities with health information technology standards to improve individual and community health. PHDSC has been invited by IHE to start a Public Health Domain at IHE. PHDSC and IHE are collaborating to enable interoperability across clinical and public health enterprises. This includes the development of interoperability standards for immunization information systems, cancer registries, chronic disease registries (diabetes) and maternal and child health (newborn screening). This also includes work on information infrastructure issues such as service-oriented architecture (SOA) for public health. PHDSC member organizations, American Immunization Registry Association (AIRA), North-American Association of Central Cancer Registries (NAACCR), Software Partners and OZ Systems, have been working on various public health projects at IHE.81 i2b2 - Informatics for Integrating Biology & the Bedside (www.i2b2.org) 2b2 (Informatics for Integrating Biology and the Bedside) is an NIH-funded National Center for Biomedical Computing based at Partners HealthCare System. The i2b2 Center is developing a scalable informatics framework that will enable clinical researchers to use existing clinical data for discovery research and, when combined with IRB-approved genomic data, facilitate the design of targeted therapies for individual patients with diseases having genetic origins. This platform currently enjoys wide international adoption by the CTSA network, academic health centres, and industry. i2b2 is funded as a cooperative agreement with the National Institutes of Health82. i2b2 is a great example of practice in establishing self-scalable thematic patient registries network based on the pear-to-pear (p2p) technology where there is no central platform facilitating the enrolment of registries, but only providing data exchange, protection and translation tools in enabling safe semantic and technical interoperability .This example shows the weaknesses of central approach and addresses barriers with incentives to registry holders, but implies higher level of their technical involvement.83

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RELATED REGISTRIES/PROJECTS/BEST PRACTICES – EU LEVEL EUBIROD (www.eubirod.eu) European Best Information through Regional Outcomes in Diabetes (EUBIROD) is a three year public health project in the field of diabetes started on the 1st September 2008, sponsored by the European Union under the Health Information Strand of the Public Health Program (DG-SANCO). EUBIROD aims to implement a sustainable European Diabetes Register through the coordination of existing national/regional frameworks and the systematic use of the BIRO technology. The scope of the EUBIROD project is to improve information to the public and formulate appropriate strategies, policies and actions and targeting appropriate sustainable coordination, in the area of health information, collection of data and information, comparability issues, exchange of data and information within and between Member States, continuing development of databases, analyses, and wider dissemination of information. In 2012, the project successfully delivered a common European infrastructure for standardized information exchange in diabetes care, for the purpose of monitoring, updating and disseminating evidence on the actual application of clinical guidelines across Europe. For this purpose, the EUBIROD project specifically defined standardized European definitions, agreed privacy-enhanced procedures and finally developed the “BIRO” system accordingly, as a suite of open source tools allowing the automatic generation of local statistical reports and the safe transfer of aggregate data to the European level, for the common good of producing international reports of diabetes indicators (Di Iorio et al 2009,2012). According to the FP7 independent evaluation conducted by the EU project “Euroreach”, “the EUBIROD project represents the most complete approach to report on structures, processes and outcomes in a specific setting”. For this reason, B. Zander and R. Busse (TUB Berline) concluded their overview by recommending the use of BIRO technology for the establishment of nationwide databases with multiple administrative registry linkages at the individual-patient level. In particular, “BIRO can be extended to further diseases and has even been specifically conceived and realized for that, since the entire platform may be parameterized to allow the computation of health indicators for a wide range of diseases” (http://www.euroreach.net/activities/workpackages/w2). The EUBIROD project delivered also a complete platform for the accurate registration of diabetes data sources, defined “Meta Register”, which includes criteria identified by the project for different areas of interest: a) to share definitions in diabetes; b) to report on data completeness and accuracy; and c) to apply common principles in the evaluation of privacy and data protection according to European legislation. The project also includes a specific training activity in the “BIRO academy”, targeting the dissemination of the approach at a global level. The aim of the EUBIROD network is to continue the organization of a European interface for the rapid publication of accurate, updated and comparable information about quality of care and outcomes in diabetes. The methodology used for the creation of EU standardized reports offers to the European Commission an opportunity to set uniform procedures that can be used repeatedly for the construction of sustainable disease registers.84 85 86

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EUROCISS (www.euro-ciss.eu) The EUROCISS Project (European Cardiovascular Indicators Surveillance Set) was set up in 2000 by a partnership of European Union (EU) countries to develop health indicators and recommendations for monitoring the burden and distribution of cardiovascular disease (CVD). The Project was financed by the European Commission within the Health Monitoring Programme (HMP). The aims of the EUROCISS project were to define indicators for monitoring CVD, to recommend standardized methods for collecting indicators in EU countries, to prepare manuals of operations describing in detail procedures and methods for easy implementation of population-based registries and CVD surveys. The achievement of these aims facilitates cross-country comparisons and assists efforts to improve the prevention and control of CVD. The countries involved in the project were Austria, Belgium, Czech Republic, Germany, Denmark, Spain, Greece, France, Finland, Hungary, Iceland, Italy, Ireland, Luxembourg, Netherlands, Norway, Portugal, Poland and United Kingdom, with the participation of European Heart Network. The EUROCISS project had two phases. First, from 2000-2003 the Project gathered experts from 14 countries in six international meetings, produced an inventory of indicators and available information sources in participating countries and set out recommendations. The main objectives of the first phase were to prioritize CVD of importance in public health, to identify specific indicators for assessing CVD mortality and morbidity and ensuing disability, to develop recommendations for collection and analysis of data for monitoring CVD in EU countries. In the second phase (2004-2007) the main objectives were to complete the technical and scientific work, begun during the first phase of the EUROCISS Project and necessary to finalize the list of indicators and the standardized procedures and methods of data collection that will assist Member States in producing reliable, valid and comparable data, to develop knowledge, tools and expertise among Member States for CVD surveillance and prevention, to assist in implementing recommendations for the development of population-based registries and surveys for monitoring temporal trends and geographical differences of CVD in Member States, to create a network of Member States with expertise in chronic diseases surveillance, which will also serve to improve the coordination of other projects funded within the Public Health Program.87 EUReMS (http://www.emsp.org/projects/eurems) European MS Platform (EMSP) is keenly aware that effective action against MS requires the ability to detect determinants of the disease, their order of importance and their impacts on quality of life for Persons with Multiple Sclerosis. With regard to Persons with Multiple Sclerosis, across European countries there is currently a widely recognized lack of data on disease epidemiology, including age and gender specific trends, actual access to new disease modifying and symptomatic treatments, long-term efficacy, safety and cost-effectiveness of disease modifying drugs, societal costs and ways to best allocate socioeconomic resources, degree of access to health care services and their quality, quality of life priorities of Persons with Multiple Sclerosis. A comprehensive approach to data collection in MS is needed addressing these issues, building on existing systems for MS data collection, but bridging their gaps and limitations by incorporating additional purposes, standardized methodological strategies and ensuring its validity across different European populations. Such an effort should be built on existing national/regional data collections, registries or cohorts and using the expertise of clinicians, researchers and patient organizations involved.

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Also, recognition that such a complex project must address all aspects in an unprejudiced way with regard to objectives, organization and technical solutions is imperative. The end goal is offering a cutting-edge research tool for improved knowledge on several aspects of MS, including the long-term effect of the services offered to Persons with Multiple Sclerosis (believed to be particularly important in times of economic constraints). In order to fulfil its aims, EUReMS’ mission is pivoted on four areas of actions - MS epidemiological and clinical surveillance across European countries, including the assessment of the "MS burden" in Europe, assessment of long-term efficacy, safety and cost-effectiveness of MS disease modifying and symptomatic treatments across European countries, assessment of provision and quality of health care services across European countries, and assessment of Persons with Multiple Sclerosis’ quality of life, the burden of symptoms and socio-economic aspects from the patient’s perspective across European countries.88 EPIRARE (www.epirare.eu) EPIRARE (European Platform for Rare Disease Registries) is a three-year project co-funded by the European Commission within the EU Program of Community Action in the field of Public Health. EPIRARE started officially on April 15, 2011. The adoption of the EU Council Recommendation on rare diseases (2009/872/CE), which recommends support of registries and databases for epidemiological purpose, is expected to result in a burst of initiatives for rare disease registration. The aim is to tackle the need for shared quality data collections for different health and healthcare purposes and the awareness of difficulties posed by their maintenance. PARENT and EPIRARE projects share several common goals, described as following: (1) Defining the needs of the EU registries and databases on rare diseases; to define the state of the art of existing registries with reference to their legal basis; organizational and IT measures used; type of data collected; compliance with the rules on personal data protection; quality assurance; operational and financial support. (2) Identifying key issues to prepare a legal basis to assess the feasibility of an EU legal instrument to allow the integration of national information sources and the collation and exchange of data at the Community level in compliance with the EU Directive 45/96 and with other relevant provisions. (3) Agreeing on a Common data set, elaborate procedures for quality control and to define a minimum data set for all rare diseases; to define criteria for quality assessment of data, data sources and procedures in the registries. (4) Agreeing on the Register and Platform Scope, Governance and long-term sustainability, to define the scope, operation and governance model of the platform, balancing the interests of relevant stakeholders and ensuring long-term sustainability of the platform. 89 EAR EFORT (www.efort.org/ear) The European Arthroplasty Register (EAR; www.ear.efort.org) is a major activity of the European Federation on National Associations of Orthopaedics and Traumatology. It is organized as a scientific non-profit society located in Austria, inside the EFORT organization. It was founded in 2001 as a voluntary network of national arthroplasty registries. Main aims of the EAR EFORT project are: to support national orthopaedic societies to establish national arthroplasty registries based on the EU-level standardization and harmonization of processes, basic research on comprehensive patient registries, the support for scientific

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activities related to arthroplasty registries and also the support of registries via EFFORT. Currently, 30 projects in 26 countries in Europe, Israel and Saudi Arabia are linked to the EAR-network. The projects are in different stages of development. The work is organized on national level as a cooperation of orthopaedic societies and national public health authorities. EAR’s main focus of activities is on outcome research and methodological research in context of arthroplasty registries. Arthroplasty Registries are powerful instruments to assess the performance of arthroplasty procedures, and a major source for scientific discussion. EAR supports the development of Arthroplasty Registries and register documentation, and aims to enhance the comparability of reports by standardization. 90 EuraHS (www.eurahs.eu) The EuraHS aims to develop and provide for all European Hernia Society’s (EHS) members an international online platform for registration and outcome measurement, an online platform for reporting early or late mesh complications, as a survey of implant materials, a set of definitions and classifications for use in clinical research on abdominal wall hernias, an uniform method of presenting outcome results in clinical studies on abdominal wall hernia repair. The registry intends to collect some preoperative data on the patient and indication, intra-operative data and outcome data (risk factor, type of hernia, date of surgery, Mesh implantation and complications). It is important that their quality equals the performance of other online applications used daily l. All data will be registered in a central database after coding, ensuring patient and surgeon anonymity. A co-worker from the central database location will contact every surgeon to obtain the outcome data after 1 and 12 months. Every participant will be able to obtain all of the data from his/her own centre. In order to increase the chances for systematic consecutive inclusion of as many patients as possible, the registration form will be provided with every purchase of a biological prosthesis and the documentation will be actively supported by the participating companies. The technical requirements for the dialogue to input data in the database are complex, including a multilingual database, a compact layout and a fast reload time. The EuraHS platform is free for use by surgeons, and only surgeons will be allowed access the platform. The surgeon uploading a case using his or her account will be the owner of the data. Moreover, a standardized set of tables and figures with the users’ data will be available and downloadable. Data can be shared in groups. A surgeon can decide to group their data with the data of other surgeons within the same hospital and therefore will be able to retrieve the overall data of the institution. Every user will be asked whether the institutional data can be shared amongst the members of the institution. The registry also aims to detect patient variables such as: complications, recurrences and quality of life. The scope of the EuraHS registry will be primary ventral hernias, incision ventral hernias and parastomal hernias in adult patients older than 18 years. Hernia operations and not patients will be registered. An attempt will be made to convince existing European hernia databases, to join the EuraHSand to collect their data on the same Internet platform.91 TREAT-NMD (www.treat-nmd.eu) TREAT-NMD is a network for the neuromuscular field that provides an infrastructure to ensure that the most promising new therapies reach patients as quickly as possible. Since its launch in January 2007 the network's focus has been on the development of tools that industry, clinicians and scientists need to bring novel therapeutic approaches through

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preclinical development and into the clinic, and on establishing best-practice care for neuromuscular patients worldwide. TREAT-NMD was initially established as a EU funded ‘network of excellence’ with the remit of ‘reshaping the research environment’ in the neuromuscular field. When a clinical trial is being planned, it is very important that patients suitable for that trial can be found and contacted quickly. The best way of ensuring this can happen is to make sure that patients' details are all collected together in a single database or "registry" that contains all the information that researchers will need, including each patient's particular genetic defect and other key information about their disease. The TREAT-NMD network is creating this kind of registry in countries across Europe and is also linking with other national registry efforts worldwide. These national registries all feed into a single global registry which combines the information from each of the national registries, and this will ensure that patients who register in their national registry can be contacted if their profile fits a clinical trial. In addition, these registries will help researchers to answer questions such as how common the individual diseases are across the world and will support other activities to improve patient care, such as the assessment of care standards in different countries. Pharmaceutical companies interested in locating patients for a clinical trial are able to request information from the TREAT-NMD global registry in a secure fashion that means that patients' details are never disclosed but companies can speedily find the information they need. The data is collected via an online form and will be stored in a central registry on the TREAT-NMD secure server. Initial data collection will include nine ‘mandatory questions’ including demographic information, NMD diagnosis, genetic results and current condition. A further six "highly encouraged questions" focus on family history, ventilation, other registries and more specific information on their disease. One of the purposes of the national registry is to define the countries NMD population and since, at the time of enrolment, patients will be at various stages of their disease course and medical care patients will be invited to update their records on a yearly basis again via an online form at this time they will also be given the opportunity to remove their data from the registry.92 EuroCMR (http://eurocmr2013.medconvent.at) The European Cardiovascular Magnetic Resonance (EuroCMR) Registry is an initiative of the ESC Working Group "Cardiovascular Magnetic Resonance". Enrolment of patients on a European level started in March 2009, resulting in the largest database on the clinical use, the impact on patient management, image quality and safety of cardiovascular MR (CMR) available so far. Including the German pilot phase (2007-2009) 31.500 patients from 58 centers in 15 countries all over Europe have been collected. In addition to the questionnaire of the pilot phase, dedicated scientific issues will be addressed by individual additional protocols.9394

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EAACI (http://www.eaaci.org/) Allergic diseases, such as asthma, hay fever, eczema, and food allergies, affect around 20% of children in European countries and early onset severe disease often persists into adulthood. The impact on quality of life and health care resources is comparable to diabetes and rheumatoid arthritis. Furthermore, immediate allergic reactions, for instance to foods and drugs, can be life threatening. European Academy of Allergy and Clinical Immunology (EAACI) is an association of clinicians, researchers and allied health professionals, dedicated to improving the health of people affected by allergic diseases. With over 7,400 members from 121 countries and 42 National Societies, EAACI is the primary source of expertise in Europe for all aspects of allergy. EAACI is aimed at allergic and immunologic diseases (such as asthma, rhinitis, eczema and occupational allergy, food and drug allergy, severe anaphylactic reactions, rheumatic and autoimmune diseases, AIDS). EAACI is an association including 41 European National Societies, more than 6,800 academicians, research investigators and clinicians aimed at promoting basic and clinical research, collecting, assessing and disseminating scientific information, functioning as a scientific reference body for other scientific, health and political organizations, encouraging and providing training and continuous education, promoting good patient care in this important area of medicine. EAACI is a non-profit organization. Income derived from fees, congress and meeting profits are devoted to current activities, research and travel awards, and initiatives of interest to members. The EAACI project is aimed at setting up a Task Force on allergic disease registries with the overall objective to provide a platform for the formation of allergic disease registries across EU country borders to develop suitable monitoring tools for use in both clinical practice and research. Goals are to help standardization of data collection on allergic diseases, diagnosis and treatment and ultimately improve allergic disease and allergen exposure management. The initial A-reg project is focused on two national allergic disease registries that are planned to grow into a pan-European registry, namely anaphylaxis and drug allergy. Two further therapy-related projects were planned to be started de novo, one on cutaneous and systemic side effects of immunotherapy and one on immunosuppressive therapies in patients with severe atopic dermatitis. EAACI states that the main advantage of starting a registry in several European reference centres at the same time is that the same methodology ensures direct comparability from the start. EAACI also plans to incorporate bio banking in all of these registries for research purposes. It is anticipated that these four projects will inform the development of further allergic disease/therapy registries, especially with regard to methodology (data collection, software use, data analysis and ethics).95 Chronic Ischemic Cardiovascular Disease (CICD) Pilot Registry (http://www.escardio.org) In the Western world, ischaemic stroke has a major public health impact as the first cause of long-term disability and the third leading cause of death. Stroke mortality ranges from 10% to 30%, and survivors remain at risk of recurrent neurological and cardiac ischaemic events. CICD registry is being undertaken to improve knowledge about the care of patients with Coronary artery disease (CAD) and peripheral artery disease (PAD). The registry will provide important data on: (1) The demographic and clinical profile of the patient population suffering from CAD and/or PAD, (2) Current treatment in daily practice, adherence to guidelines and evidence-based

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practice, (3) The changing patterns of CAD and/or PAD management during the registry, (4) Follow-up, (5) Variations in management of CAD and/or PAD patients according to geography, type of physician, patient characteristics, (6)The determinants of long-term prognosis, (7) The population of this registry is intended to reflect the spectrum of patients with CAD and/or PAD. This information will help to improve the management of patients suffering from CV disease, which represents the number one killer in western countries96 The registry will provide important data on following: demographic and clinical profile of the patient population suffering from CAD and/or PAD; evidence-based daily practice, adherence to guidelines; changing patterns of CAD and/or PAD management (related to geography and patient/care type); the determinants of long-term prognosis. This information from this registry should support improvement of patient management suffering from cardiovascular diseases.97 EGHI (http://ec.europa.eu/health/strategy/implementation/hic/) The Experts Group on Health Information (EGHI) is a consultative structure with representatives from all the Member States to support the overall implementation mechanisms for the health strategy with regard to health information. In particular, the Experts Group on Health Information should work together with the Commission to agree on needs and solutions for European health information and reconcile the technical issues and resource constraints of this information with the overall EU policy and strategic needs, assist in defining and overseeing technical work needed to achieve this work, act as a platform for cooperation and collaboration on health information at a European level. Technical groups are being established to take forward work in specific areas, and would report back to the EGHI. These technical groups have a specific and time-limited mandate to achieve a specific result, rather than becoming a standing structure. The ongoing operational technical groups are Task Force on Health Expectancies, Subgroup on the European Health Examination Survey and European Community Health Indicators Monitoring Group. The EU Health strategy is focused towards fostering good health in an ageing Europe, protecting citizens from health threats, supporting dynamic health systems and new technologies. For each objective, the Commission has several committees or working groups, which bring together national governments, local and regional authorities, stakeholders, national and international organizations and other experts. The strategy aims at delivering concrete results in improving health. It is implemented in tandem with Member States, regions and stakeholders, through a number of financial and organizational instruments created by the Commission.98 ECAB (http://www.ecabeurope.eu/) ECAB project brings together a team of high level experts with very extensive experience in the area of European health policy. The thirteen-partner project consortium combines geographical and disciplinary diversity with academic rigor and policy relevance. The scope of ECAB project is to identify and analyze arrangements of cooperation between actors located in different EU countries that aim to transfer patients, providers, products, services, funding or knowledge across the border which separates them. Current gaps in documentation of already existing cross-border collaboration activities as regards geographical coverage, availability and quality of data need to be addressed. On this basis a systematic in-depth analysis of the potential impact of cross-border collaboration on the

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wider healthcare system should be undertaken. Primary data collected in this project should close existing gaps and the findings of this research should enable national and European decision-makers to correctly assess the scale of existing cross-border care cooperation and its potential implications for the national healthcare system. The aim of ECAB is to facilitate a process whereby Europe’s citizens can make informed choices about whether to seek health care in another Member State and, if they so choose, to ensure that the administrative and clinical processes are straightforward and ensure continuity of care. It takes as its starting point the recent draft Directive on Patients’ Rights, augmented by the existing body of research on cross-border care. It then focuses on those areas where the necessary information is incomplete and seeks to fill the gaps. It is equally important to state what it does not do. It does not seek to quantify the scale of movement because our earlier research reveals this to be a dynamic area where data are often unavailable and rapidly become out of date. ECAB firstly examines five aspects of health care delivery where it will be necessary for procedures to be compatible if patients are to be assured that the care they receive is safe, of adequate quality, and capable of providing continuity where some parts of the overall care process are provided in different Member States. These are provisions with regard to the continuing quality of health professionals, treatment pathways, public reporting of quality, content and scope of medical records, medical prescribing. The objectives of ECAB are to undertake a review of the key policy directions and results of EU-funded R&D initiatives and analyze them from two perspectives (to have policy recommendations addressed issues pertinent to the development and implementation of discharge summaries in the context of cross-border care, to have EU-funded R&D efforts thus far produced results that could be utilized in focusing further policy and deployment efforts in the area of discharge summaries), to undertake a comparative assessment of hospital discharge summaries, through a systematic literature review of hospital discharge summary (systems) in Europe, a mapping exercise of hospital discharge summary (systems) in Europe; and a comparative assessment of hospital discharge summaries across Europe, to describe the nature of information supplied to patients and referring physicians on discharge from hospital in each Member State. The methodology used is the systematic review of electronic medical records / systems of health data collection in EU Member States, comparative assessment of hospital discharge summaries and research of policy recommendations on improving and standardizing public medical records across the EU.99 eHGI (www.ehgi.eu) The European eHealth Governance Initiative (eHGI) supports cooperation between Member States at Political Governance levels and eHealth Stakeholders. The European eHealth Governance Initiative ultimately aims at improving the health status of European citizens, the quality and continuity of care and the sustainability of European Health Systems. By improving eHealth governance, through the coordination of the Member States and the European eHealth policies, an interoperable eHealth structure will be built within the EU. The eHealth Governance Initiative (eHGI) is a project composed of a Joint Action (co-funded by DG SANCO) and a Thematic Network (funded by DG INFSO).

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The eHealth Governance Initiative is focusing on achieving an eHealth governance structure, in particular by developing strategies, priorities, recommendations and guidelines on how to develop eHealth in Europe in a coordinated way and joining efforts, involving stakeholders, especially patients and health professionals, in the hope of ensuring continuity of the healthcare provided either at home or crossing borders. The eHealth Governance Initiative seeks a strong coordinated political leadership and the integration of eHealth into health policies. Furthermore, the eHealth Governance Initiative will support the political process and governance structures in setting the right priorities, developing strategies, recommendations and guidelines on how to promote an interoperable and sustainable eHealth implementation in Europe. The Joint Action aims to support the eHealth Governance Initiative (eHGI) as the platform for technical and political co-operation between Member States on eHealth including their relationships with eHealth Stakeholder Groups which include EU level organizations representing health professionals, hospitals, patients, standards developing organizations and industry. The results of JA (recommendations, guidelines) will furthermore support the work of the eHealth Network set up in accordance with Art.14 of the Directive on patients' rights in cross-border healthcare. In the framework of the eHealth Network, the Commission and Member States will discuss and agree on political and strategic issues related to eHealth, in accordance with Art.14 of the Directive, including political prioritization in the eHealth interoperability roadmap and its implementation. To ensure coordination, coherence and consistency between the political level (the eHealth Network) and the expert level (the JA on eHGI), the eHealth Network shall provide guidance for the work of the Joint Action as appropriate.100 epSOS (www.epsos.eu) The epSOS key goals are to improve the quality and safety of healthcare for citizens when travelling to another European country. Moreover, it concentrates on developing a practical eHealth framework and ICT infrastructure that enables secure access to patient health information among different European healthcare systems. The epSOS strives to contribute patient safety and reducing the frequency of medical errors as well as to provide quick access to documentation. In emergency situations, this documentation provides the medical personnel with life-saving information and reduces (sometimes needless) repetition of diagnostic procedures. In the first phase epSOS will try to access important medical data for patient treatment, make a platform for cross-border use of electronic prescriptions (“ePrescription” or “eMedication” systems). In the second phase (enlargement phase), epSOS will integrate the 112 emergency services, integrate the European Health Insurance Card (EHIC). EpSOS is aimed at giving patients in Europe the opportunity to use cross-border eHealth services when seeking healthcare in participating epSOS pilot countries - whether as tourists, business travellers, commuters or exchange students.101 EudraGMP (http://eudragmp.ema.europa.eu) EudraGMP is the name for the Community database on manufacturing and import authorizations and Good Manufacturing Practice (GMP) certificates. The European

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Medicines Agency launched the first release in April 2007 and future releases will include planning of inspections in third countries, alerts for quality defects and in addition it is expected to also include information on Wholesale as a result of new Community legislation on anti-falsification. They are working on significantly improving information and coordination sharing in the area of authorizations and GMP certificates between national competent authorities. This is done by eliminating duplication of work and the administrative paper exchange between national competent authorities. It also provides a future platform for facilitating collaboration with international regulatory partners. Authorization and certificate formats together with relevant procedures are harmonized and published in the Compilation of Community Procedures. The European legislation does not require mandatory routine GMP inspections for substance manufacturers. Therefore, the absence of a GMP certificate for a manufacturer of active substances in EudraGMP does not automatically mean that the manufacturer does not comply with GMP. To ensure that the Agency’s system works effectively, it works closely with its partners and stakeholders, and is a proactive member of important networks in Europe and beyond. These include the European Commission, the European Parliament and the Member States, as well as other decentralized agencies of the European Union (EU); medicines regulators outside of the EU; patient and consumer organizations; organizations representing healthcare professionals; the pharmaceutical industry; international organizations; multi-partner networks; health technology assessment bodies. 102 EUnetHTA (http://www.eunethta.eu/) EUnetHTA is a network of government appointed organizations and a large number of relevant regional agencies and non-for-profit organizations that produce or contribute to health technology assessment (HTA) in 32 European countries including 26 EU Member States. It focuses on HTA in Europe to facilitate efficient use of resources available for HTA, to create a sustainable system of HTA knowledge sharing, and to promote good practice in HTA methods and processes. EUnetHTA aims at developing reliable, timely, transparent and transferable information to contribute to HTA in European countries. This collaboration started in 2008. The aims of the HTA are to support collaboration between European HTA organizations bringing added value to healthcare systems. This network provides an independent and science-based platform for HTA agencies in countries across Europe to exchange and develop HTA information and methodology. They provide an access point for communication with stakeholders to promote transparency, objectivity, independence of expertise, fairness of procedure and appropriate stakeholder consultations and to develop alliances with contributing fields of research to support a stronger and broader evidence base for HTA while using the best available scientific competence. The project has two databases: EUnetHTA Planned and Ongoing Projects (POP) Database, and EVIDENT Database. The POP database allows HTA agencies to share with each other information on planned and ongoing projects conducted at each agency. The aim of the database is to reduce duplication and facilitate collaboration among HTA agencies. Access to the POP database is currently restricted to EUnetHTA Partners and Associates who contribute to the POP database. The project does not gather the data as in other registries. It comprises of HTA cases database, hidden to public and left only to project partners and associates, the database is developed and maintained by DIMDI, Partner country-Germany Partner. The main value of the project is the improvement in number of available HTA cases as help for

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countries where HTA is not fully implemented in reimbursement process, or where it is still in project and note regulatory level.103 EUDRANET (http://ec.europa.eu/idabc/en/document/2291/5926.html) EUDRANET is a European human and veterinary pharmaceuticals telecommunication network offering Information and Communication Technology (ICT) services that allows scientific experts, those working on pharmaceutical business processes and policy makers to have a secure and well structured electronic environment to 'meet', exchange information and work together on a pan-European scale. Although managed by the European Medicines Evaluation Agency (EMEA), the Eudra "family" of applications (such as EUDRAVIGILANCE and EudraTrack) comes under the overall responsibility of the Pharmaceuticals and Cosmetics Unit within the European Commission's DG Enterprise. These applications are provided in collaboration with the EMEA and the national authorities responsible for pharmaceuticals, which make 28 organizations in total. EUDRANET aims to provide appropriate secure services for inter-Administration data interchange and for exchanges between Administrations and industry. One of EUDRANET's main objectives is to enable the electronic exchange of information between the European Commission, EMEA and the national regulatory authorities responsible for pharmaceuticals across the EU Member States. It aims to achieve this through the use of TESTA as its backbone. A second key objective is to provide a service for secure and managed communication over the Internet between European Administrations and pharmaceutical companies. This has been achieved through the implementation of EudraLink, a software tool designed to facilitate the secure transmission of information or documents between the EU Member States, the European Commission and the pharmaceutical industry. Due to this network, elements of the marketing authorization procedures can be carried out over the Internet. EudraLink seeks to ensure the confidential and rapid granting of these authorizations. Thirdly, EUDRANET exists to host and provide access to Community databases in pharmaceuticals. This includes the European Experts Database and Pharmacovigilance database (EUDRAVIGILANCE). Finally, and most importantly, EUDRANET aims to provide a collaborative group work environment and business cooperation tools such as desktop video conference.104

BURQOL-RD (http://burqol-rd.com/) BURQOL-RD is a 3 year project under the 2nd Program of Community Action in the Field of Public Health that commenced in April 2010 and is promoted by the DG SANCO. The main aim of BURQOL-RD is to generate a model to quantify the socio-economic costs and Health Related Quality of Life (HRQOL), of both patients and caregivers, for up to 10 rare diseases in different European countries. This model will be adaptable and sufficiently sensitive to capture the differences in the distinct Health and Social Care Systems in the EU Member States. The information generated by the BURQOL-RD consortium should help designing future policies in the area of rare diseases, which will ultimately have positive benefits for EU citizens’ health, both patients and caregivers. The goals of this project are to readily transfer the protocols established to other RD and to other countries, to compare the availability and access to specific health resources for specific RD in each country, and to explore the potential relationships between HRQL and access to healthcare resources. BURQOL-RD is targeted at 10 rare diseases - Cystic fibrosis, Prader-Willi Syndrome, Haemophilia, Duchenne Muscular Dystrophy, Epidermolysis Bullosa, Fragile X Syndrome, Scleroderma, Mucopolysaccharidosis,

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Juvenile idiopathic arthritis and Histiocytosis. The objectives of BURQOL-RD are to generate a methodological framework to measure the socio-economic burden of RD, to define a methodological framework to measure the HRQOL of RD, to develop unified instruments to gather information on the socio-economic burden and HRQOL of RD throughout Europe, to perform a pilot study measuring the socio-economic burden and HRQOL for selected RD, to refine and package the tools developed for continued and more extensive costs and HRQOL studies of RD. The fundamental beneficiary of the results of this project are families and caregivers of those affected by RD.105 HoNCAB A Commission granted second Health Programme project to support creation of a pilot network of hospitals related to payment of care for cross-border patients. The main objectives are to determine the patients' rights in terms of access to cross-border health assistance and entitlement to reimbursement of such treatment, to ensure access and provision of safe, high-quality, efficient and quantitatively adequate healthcare abroad, to support collaboration between Member States regarding healthcare, and to obtain a better understanding of the financial and organizational requirements that may arise as a result of a patient receiving healthcare outside the Member State of affiliation. HoNCAB is setting up a web-based database to collect and exchange information as well as a pilot network to test and implement the knowledge management systems on administrative issues related to payment of care and patient experience of cross‐border care with a focus on reimbursement issues. HIQA (www.hiqa.ie) The Health Information and Quality Authority is the independent Authority established in May 2007 to drive continuous improvement in Ireland’s health and social care services. HIQA is an independent authority responsible for driving quality, safety and accountability in residential services for children, older people and people with disabilities in Ireland. HIQA develops standards, monitor compliance with standards and carries out investigations where there are reasonable grounds to do so. One of HIQA functions is to carry out national Health Technology Assessments (HTA). HIQA is responsible for setting standards on safety and quality for health and social care services. Under legislation, these standards are applicable to services provided by or on behalf of the Heath Services Executive (HSE) as well as services provided by a nursing home. Examples include but are not limited to: acute hospitals, community hospitals, nursing homes/hospitals, district hospitals, health centres, dental clinics, childcare residential services, primary care services, home care, etc. HIQA is developing Health Information Technical Standards to ensure that there can be consistency in capturing and sharing of health information records. Health Information Technical Standards support interoperability between systems and meaningful sharing of data. These include data definitions, clinical concepts and terminologies, coding and classifications, messaging specifications, the Electronic Health Record, and security. Health information standards are intended to remove ambiguity and ensure that there can be mutual understanding. Common data definitions are required in order to support the collection of nationally consistent and comparable data on the health status of the community, health determinants and health services (including performance). HIQA

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developed the General Practice Messaging Standard in March 2010 and a revised version was published in November 2011. This defines the structure and content of electronic messages used in the transfer of information to and from general practices and acute care and out of hours care. The standard is a local customization of the international messaging standard developed by the Health Level Seven (HL7) organization, an international standards development agency specializing in messaging standards for healthcare.106107 SALUS (http://www.salusproject.eu/) Scalable, Standard based Interoperability Framework for Sustainable Proactive Post Market Safety Studies (SALUS) aims to provide a standard-based interoperability framework that will enable execution of safety studies for mining and analyzing real-time patient data in communication with disparate heterogeneous Electronic Health Record (EHR) systems. The goal of SALUS is to provide:

Functional interoperability profiles enabling exchange of EHRs Semantic interoperability solutions enabling meaningful interpretation of the

exchanged EHRs Security and Privacy mechanisms ensuring EHRs are shared in an ethical and safe

way A novel framework for open-ended temporal pattern discovery for safety studies on

top of EHR Systems Implementation of high potential use cases enabling secondary use of EHRs for post

market safety studies108 There are also other notable examples of state-of-the-art patient registry usage. We will note them briefly in the following text. Australia: Operating Principles and Technical Standards for Clinical Quality Registries. http://www.crepatientsafety.org.au/registries/operating_principals_technical_standards_nov08.pdf United Kingdom: Disease Registers in England. http://www.sepho.org.uk/download/Public/5445/1/disease_registers_in_england.pdf Health and Social Care Information Centre http://systems.hscic.gov.uk/ http://www.hscic.gov.uk/collectingdata Canada: Canadian Institute for Health Information http://www.cihi.ca/CIHI-ext-portal/internet/EN/Document/standards+and+data+submission/data+holding+metadata/data_holdings_metadata

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New Zealand: http://www.health.govt.nz/nz-health-statistics/national-collections-and-surveys/collections Ireland: IPPOSI – Towards a national strategy for patient registries http://www.ipposi.ie/index.php/information-centre/patient-registries/179-towards-a-national-strategy-for-patients-registries-report

SEARCH METHODOLOGY After searching for various sources of information on the Internet, including the “grey literature” we opted for performing a classic literature review approach with the biomedical scientific databases. In the first step, we wanted to test the versatile key words in MeSH terms and versatile results deriving from different wording and wording combination. The MeSH term for patient registry is “registries” and we have selected all of the offered sub terms.

• Inclusion criteria were all of EU countries and keywords reflecting the Scenario2 as well as opinion papers (only when addressing the subject of interest)

• Exclusion criteria: clinical studies, non EU countries, non patient registry relevant

We have tested the wording registries and drugs and/or devices with selected words (diabetes, cardiovascular, arthroplasty, hernia and rare diseases) with word Europe and /or agents. Under each of the term/wording combination we have put number of resulting references, and where possible, final results of references valid according to criteria (Table 1). Results below should serve as reference point when performing target LitRev. Also, for several wording results we have selected the references according to the above inclusion/exclusion criteria. The searches were conducted during 2012 and updated at the beginning of 2013, March 20th being the final day. The databases that were searched are shown in Table 1 with the references found in each database listed. Afterwards, the search continued within the following databases: PubMed, Web of Science, Scopus. We defined as the most appropriate search terms: “interoperability”, “registry” (with various versions, e.g. register, registers, registries, etc.) and “best practices” in the mentioned databases, while in PubMed we also used the MeSH term "Practice Guidelines as Topic". We chose to narrow the search in this manner in order to identify articles as specific as possible for the description of best practices in the field of registry establishment and maintenance (Table 2). In the next step, in order to broaden the search, we have removed the “best practice”/ "Practice Guidelines as Topic" term from the search, and we found 36 references in the PubMed database, 81 references in the Web of Science database, and 252 in Scopus. While this approach yielded more results, after the screening of those articles, we found that

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many of those articles were not specific to our field of interest or related to other aspects of registries than we were interested in and have therefore decided to try another search strategy. We included the term “metadata registry” OR “metadata registries” instead of the term “registry” and when combining it with the “interoperability” term, we obtained the results shown in Table 3.

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Table 1: Results of various searches in PubMed

CRITERIA Results

"Registries"[Mesh] 46912

("Registries"[Mesh]) AND "Europe"[Mesh] 18561

("register"[Title] OR "registry"[Title] OR "registers"[Title] OR "registries"[Title]) AND "Europe"[Mesh]

5657

("register"[Title] or "registry"[Title] or "registers"[Title] or "registries"[Title]) and "Patient"[Title] and "Europe"[Mesh]

128

("register"[Title] or "registry"[Title] or "registers"[Title] or "registries"[Title]) and "Patient"[Title]

368

("register"[Title] or "registry"[Title] or "registers"[Title] or "registries"[Title]) and ("patient"[Title] or "disease"[Title] or "device"[Title] or "service"[Title])

1283

("register"[Title] or "registry"[Title] or "registers"[Title] or "registries"[Title] or "registration"[Title]) and ("patient"[Title] or "disease"[Title] or "device"[Title] or "service"[Title])

1619

("register"[Title] or "registry"[Title] or "registers"[Title] or "registries"[Title] or "registration"[Title]) and ("patient"[Title] or "disease"[Title] or "device"[Title] or "service"[Title] or "care"[Title] or "implant"[Title] or "chronic"[Title] or "rare"[Title])

2327

("register"[Title] OR "registry"[Title] OR "registers"[Title] OR "registries"[Title] OR "registration"[Title]) and ("patient"[Title] OR "disease"[Title] OR "device"[Title] OR "service"[Title] OR "care"[Title] OR "implant"[Title] OR "chronic"[Title] OR "rare"[Title]) AND "Europe"[Mesh]

797

"cross-border"[Title] AND "Europe"[Mesh] 65

("Registries"[Mesh]) AND "Electronic Health Records"[Mesh] 63

(( "Arthroplasty/adverse effects"[Mesh] OR "Arthroplasty/classification"[Mesh] OR "Arthroplasty/contraindications"[Mesh] OR "Arthroplasty/economics"[Mesh] OR "Arthroplasty/instrumentation"[Mesh] OR "Arthroplasty/legislation and jurisprudence"[Mesh] OR Arthroplasty/methods"[Mesh] OR "Arthroplasty/mortality"[Mesh] OR "Arthroplasty/nursing"[Mesh] OR "Arthroplasty/psychology"[Mesh] OR "Arthroplasty/rehabilitation"[Mesh] OR "Arthroplasty/standards"[Mesh] OR "Arthroplasty/statistics and numerical data"[Mesh] OR "Arthroplasty/trends"[Mesh] OR "Arthroplasty/utilization"[Mesh] )) AND ( "Registries/classification"[Mesh] OR "Registries/economics"[Mesh] OR "Registries/ethics"[Mesh] OR "Registries/history"[Mesh] OR "Registries/legislation and jurisprudence"[Mesh] OR "Registries/methods"[Mesh] OR "Registries/standards"[Mesh] OR "Registries/statistics and numerical data"[Mesh] OR "Registries/utilization"[Mesh] )

47

"Arthroplasty" AND "Registries" 523

"Arthroplasty implants" AND "Registries" 1

"Arthroplasty" and "Registries" and "Europe" 14

"Hernia/rehabilitation"[Mesh] OR "Hernia/therapy"[Mesh] )) AND ( "Registries/classification"[Mesh] OR "Registries/economics"[Mesh] OR "Registries/ethics"[Mesh] OR "Registries/history"[Mesh] OR "Registries/legislation and jurisprudence"[Mesh] OR "Registries/methods"[Mesh] OR "Registries/organization and administration"[Mesh] OR "Registries/standards"[Mesh] OR "Registries/statistics and numerical data"[Mesh] OR "Registries/utilization"[Mesh] )

20

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"HERNIA" and "Registries" 170

"HERNIA" and "Registries" and "Europe" 15

"orphan drugs" AND " REGISTRIES" 13

"RARE DISEASES" AND "drugs" AND "REGISTRIES" 13

"Rare Diseases/drug therapy"[Mesh]and "registries" 12

"DIABETES drugs" AND "REGISTRIES" 1

"Diabetes Mellitus/drug therapy"[Mesh] and "registries" 215

Table 2: Overview of obtained references on the subject of interoperability, and best practices in registries

Database References

PubMed (1)

Lim Choi Keung SN, Ogunsina I, Rossiter J, Langford G, Tyler E, Arvanitis TN. Standardised representation of healthcare information in secondary care research: a Central England case study. Stud Health Technol Inform. 2012;180:529-33.

Web of Science (1)

Ayres EJ, Hoggle LB. Advancing practice: Using nutrition information and technology to improve health - the nutrition informatics global challenge. Nutrition & Dietetics. 2012 Sep;69(3):195-7.

Scopus (2)

Henninger, A.E., Gibson, R., Oates, W., Gravitz, P., Burnette, M., Hutt, R., Reed, J., Shook, T., Lightner, M.The development of a DoD M&S Standards Profile (2010) Spring Simulation Interoperability Workshop 2010, 2010 Spring SIW, pp. 345-353

Lampathaki, F., Kroustalias, N., Koussouris, S., Charalabidis, Y., Psarras, J. Implementing interoperability infrastructures: Issues and challenges from the citizens' base registry in Greece (2010) Proceedings of the Annual Hawaii International Conference on System Sciences, art. no. 5428278,

Table 3: Overview of obtained references on the subject of interoperability and metadata registries

Database References

Pubmed (3)

Park YR, Kim JH. Achieving interoperability for metadata registries using comparative object modelling. Stud Health Technol Inform. 2010;160(Pt 2):1136-9.

Bruland P, Breil B, Fritz F, Dugas M. Interoperability in clinical research: from metadata registries to semantically annotated CDISC ODM. Stud Health Technol Inform. 2012;180:564-8.

Ngouongo SM, Löbe M, Stausberg J. The ISO/IEC 11179 norm for metadata registries: Does it cover healthcare standards in empirical research? J Biomed Inform. 2012 Dec 14. doi:pii: S1532-0464(12)00182-7. 10.1016/j.jbi.2012.11.008. [Epub ahead of print]

Web of Science (17)

Heery R. Information gateways: collaboration on content. Online Information Review. 2000;24(1):40-5.

Ruggieri AP, Elkin P, Chute CG. Representation by standard terminologies

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of health status concepts contained in two health status assessment instruments used in rheumatic disease management. Journal of the American Medical Informatics Association. 2000:734-8.

Polydoratou P, Nicholas D. Familiarity with and use of metadata formats and metadata registries amongst those working in diverse professional communities within the information sector. Aslib Proceedings. 2001 Sep;53(8):309-24.

Fischer T. Metadata registries: Current status and future developments. Zeitschrift Fur Bibliothekswesen Und Bibliographie. 2003 Jul-Aug;50(4):199-204.

Jeong DW, Kim YG, Baik DK. SQL/MDR: Query language for consistent access of metadata registries based on SQL3. In: Li Q, Wang G, Feng L, editors. Advances in Web-Age Information Management: Proceedings2004. p. 239-48.

Choi OH, Lim JE, Baik DK. MDR-based framework for sharing metadata in ubiquitous computing environment. In: Yang LT, Amamiya M, Liu Z, Guo M, Rammig FJ, editors. Embedded and Ubiquitous Computing - Euc 20052005. p. 858-66.

Jeong D, Kim YG, In HP. Quantitative evaluations on the query modelling and system integrating cost of SQL/MDR. Etri Journal. 2005 Aug;27(4):367-76.

Jeong D, Kim YG, Park SH, Baik DK. Uniformly handling metadata registries. In: Dosch W, Lee RY, Wu C, editors. Software Engineering Research, Management and Applications2005. p. 81-91.

Na HS, Choi OH. FSMI: MDR-based metadata interoperability framework for sharing XML documents. In: Baik DK, editor. Systems Modeling and Simulation: Theory and Applications2005. p. 343-51.

Jeong D, Han Y. Resolving the semantic inconsistency problem for ubiquitous RFID applications. In: Ma J, Jin H, Yang LT, Tsai JJP, editors. Ubiquitous Intelligence and Computing, Proceedings2006. p. 1134-43.

Kock YG, Jung GD, Choi YK. Data grid system based on agent for interoperability of distributed data. In: Shi ZZ, Sadananda R, editors. Agent Computing and Multi-Agent Systems2006. p. 162-74.

Nadkarni PM, Brandt CA. The common data elements for cancer research: Remarks on functions and structure. Methods of Information in Medicine. 2006;45(6):594-601.

Tsiknakis M, Brochhausen M, Nabrzyski J, Pucacki J, Sfakianakis SG, Potamias G, et al. A semantic grid infrastructure enabling integrated access and analysis of multilevel biomedical data in support of postgenomic clinical trials on cancer. Ieee Transactions on Information Technology in Biomedicine. 2008 Mar;12(2):205-17.

King T, Merka J, Narock T, Walker R, Bargatze L. A registry framework and Rosetta attributes for distributed science. Earth Science Informatics. 2010 Jun;3(1-2):127-33.

Liu DH, Wang X, Pana F, Yang P, Xu YY, Tang XJ, et al. Harmonization of health data at national level: A pilot study in China. International Journal of Medical Informatics. 2010 Jun;79(6):450-8.

Park YR, Kim HH, Seo HJ, Kim JH. CDISC Transformer: a metadata-based

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transformation tool for clinical trial and research data into CDISC standards. Ksii Transactions on Internet and Information Systems. 2011 Oct;5(10):1830-40.

Park YR, Kim H, An EY, Kim HH, Kim JH, Park RW, et al. Establishing semantic interoperability in the course of clinical document exchange using internation standard for metadata registry. Journal of the Korean Medical Association. 2012 Aug;55(8):729-40.

Scopus (34 – 6 duplicates removed)

Blanchi C, Petrone J. Distributed interoperable metadata registry. D-Lib Magazine. 2001;7(12).

Cornwell IH, Raines A, Booth JH, editors. Results of ITS Metadata Registry trial2004; London.

DC-2006 - International Conference on Dublin Core and Metadata Applications: "Metadata for Knowledge and Learning"2006; Manzanillo, Colima.

Jeong D, Jing Y, Kim J, Baik DK, editors. A framework for application-independent semantic management for ubiquitous computing environment2006; Seattle, WA.

Ki YK, Kim JW, Baik DK, editors. A traffic accident detection model using metadata registry2006; Seattle, WA.

Lim JE, Choi OH, Na HS, Baik DK, editors. A methodology for semantic similarity measurement among metadata based information system2006; Seattle, WA.

Swain DE, Wagy J, McClelland M, Jacobs P, editors. Developing a metadata schema for CSERD: A computational science digital library2006; Chapel Hill, NC.

Winters LS, Gorman MM, Tolk A, editors. Next generation data interoperability: It's all about the metadata2006; Orlando, FL.

Burnett M, Weinstein B, Mitchell A, editors. ECHO - Enabling interoperability with NASA earth science data and services2007; Barcelona.

Kim JD, Jeong D, Jing Y, Baik DK, editors. UbiMDR: Supporting application-independent semantic interoperability for ubiquitous applications2007; Guangzhou.

Li JH, Gao JX, Dong JN, Wu W, Hou YF. A metadata registry for metadata interoperability. Data Science Journal. 2007;6(SUPPL.):S379-S84.

Yutao M, He K, Liu W, Tian J, editors. A grid-oriented platform for software component repository based on domain ontology2007; Salt Lake City, UT.

Broyles DH, Moore JS, editors. Net-centric information sharing for M&S2008; Orlando, FL.

Kim JD, Jeong D, Baik DK, editors. Semantic interoperability for RFID service framework2008; Busan.

Kook YG, Kim RYC, Choi YK. Multi-agent system using G-XMDR for data synchronization in pervasive computing environments. Kuala Lumpur2009. p. 297-309.

Liu H, Yang JY, Liu MS, editors. Research on metadata registry based on web service2009; Baoding.

Mitchell A, Ramapriyan H, Lowe D, editors. Evolution of web services in

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EOSDIS - Search and order metadata registry (ECHO)2009; Cape Town.

Rehak DR, Nicholas N, Ward N. Service-oriented models for educational resource federations. D-Lib Magazine. 2009;15(11-12).

Gustavson P, Dumanoir P, Blais C, Daehler-Wilking R, editors. Discovery and reuse of modelling and simulation assets2010; Orlando, FL.

King T, Merka J, Narock T, Walker R, Bargatze L. A registry framework and Rosetta attributes for distributed science. Earth Science Informatics. 2010;3(1):127-33.

Park YR, Kim JH, editors. Achieving interoperability for metadata registries using comparative object modeling2010; Cape Town.

Barateiro J, Borbinha J, editors. Integrated management of risk information2011; Szczecin.

Han MJ, Wacker M, Dartt J, editors. Testing resource description and access (RDA) with dublin core2011; The Hague.

Kim JD, Son J, Baik DK, editors. MMOR: A mapping method for ontology registration to improve XMDR2011; Paris.

Bruland P, Breil B, Fritz F, Dugas M, editors. Interoperability in clinical research: From metadata registries to semantically annotated CDISC ODM2012; Pisa.

Jeong D. Framework for seamless interpretation of semantics in heterogeneous ubiquitous sensor networks. International Journal of Software Engineering and its Applications. 2012;6(3):9-16.

Lim S, Seo T, Lee C, Shin S. Study on the international standardization for the semantic metadata mapping procedure. Busan2012. p. 243-9.

MnNgouongo S, Stausberg J, editors. A ClaML-based interface for the import of monohierarchical classifications2012; Pisa.

We performed the review of available data from these articles and found valuable information for the designation of pilot RoR. However, since these articles are still relatively too specific and do not provide country-specific experiences we opted to include various other references provided by other sources such as Google Scholar and Google itself, using similar searching techniques as described above. The other reasons were valuable experiences from various other projects described in this review, both from Associated Projects Group and other projects and organizations that are described in more detail with the information obtained from sources other than classic peer-reviewed literature (such as websites of national societies, various projects, and other grey literature). In conclusion, while the search of biomedical literature regarding the interoperability of registries did provide important information for the implementation of RoR, the information obtained was not sufficient regarding the background description of projects and registries that will be involved in the designation of RoR and this information was obtained through more conventional sources.

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Appendix I: Other related metadata Standards and Organizations Current schemes

CDWA (Categories for the Description of Works of Art)

CSDGM (Content Standard for Digital Geospatial Metadata)

DC (Dublin Core)

EAD (Encoded Archival Description)

IEEE LOM (Learning Objects Metadata)

MARC/XML

METS (Metadata Encoding & Transmission Standard

MODS (Metadata Object Description Schema)

ONIX 3.0

TEI P4 (Text Encoding Initiative)

VRA Core 4.0 (Visual Resources Association)

XOBIS (XML Organic Bibliographic Information Schema) Crosswalks

EAD crosswalks / from LC

Mapping between metadata formats / from UKOLN

MARC mapping to MODS 3.1 / from LC

MARC to Dublin Core / from LC

Metadata mappings / from MIT

Metadata standards crosswalks / from the Getty Institute

ONIX to MARC21 / from LC

University of Oregon Art & Architecture Images : crosswalks to VRA 3.0 & DC

UNTL Digital Products Unit crosswalks / from the University of North Texas Libraries

VRA Core 3.0 to MARC21 Attribute values sources

Date and time formats / W3C

DCMI type vocabulary

MARC value list for realtors and roles

Mime media types

MODS identifier attributes Content standards

Cataloging cultural objects (CCO)

Describing archives: A content standard (DACS)

AACR2 (via Cataloger's Desktop- requires password) XML

A gentle introduction to XML / from TEI

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References 1Wallgren A, Wallgren B. Register-based Statistics: Administrative Data for Statistical Purposes, Wiley Series in Survey Methodology, 2007. 2Wallgren A, Wallgren B. Register-based Statistics: Administrative Data for Statistical Purposes, Wiley Series in Survey Methodology, 2007. 3Wallgren A, Wallgren B. Register-based Statistics: Administrative Data for Statistical Purposes, Wiley Series in Survey Methodology, 2007. 4 Newton J, Garner S. Disease Registers in England/A report commissioned by the Department of Health Policy Research Programme in support of the White Paper entitled Saving Lives: Our Healthier Nation, Institute of Health Sciences, 2002. University of Oxford. 5 Porta M (ed), A dictionary of Epidemiology. New York. Oxford University Press. 5th edition 2008) 6Olsen J, Basso O and Sørensen HT. What is a population-based registry?, Scand J Public Health 1999;27:78 7http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=12 8AHRQ. Registries for evaluating patient outcomes: a users’ guide, No 10-EHC049-1, September 2010. http://www.ncbi.nlm.nih.gov/books/NBK49448/ 9EM B. The current and future use of registers in health information systems. Geneva: World Health Organization. Geneva: World Health Organization, 1974. 10(AHRQ) Registries for Evaluating Patient Outcomes: A User’s Guide, 3Ed, Volume 1. In: Guide, editor, 2012. 11Patterson MC, Mengel E, Wijburg FA, Muller A, Schwierin B, Drevon H, Vanier MT, Pineda M. Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis. 2013 Jan 16;8:12http://www.ojrd.com/content/pdf/1750-1172-8-12.pdf 12https://www.lsdregistry.net/fabryregistry/hcp/understd/freg_hc_u_aboutreg.asp 13https://www.eimd-registry.org/ 14Wennberg DE, Lucas FL, Birkmeyer JD et al. Variation in carotid endarterectomy mortality in the Medicare population. JAMA 1998;279:1278-81 15MacIntyre K, Capewell S, Stewart S et al. Evidence of improving prognosis in heart failure: trends in casefatality in 66 547 patients hospitalized between 1986 and 1995. Circulation 2000;102:1126–31 16Hutchins LF, Unger JM, Crowley JJ et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061-7. 17https://research.tufts-nemc.org/cear4/ 18Baim DS MR, Kereiakes DJ, et al. Postmarket surveillance for drug-eluting coronary stents: a comprehensive approach. Circulation 2006;(113):891–7. 19Sedrakyan A M-DM, Norman SL, et al. A framework for evidence evaluation and methodological issues in implantable device studies. Med Care. 2010;48(6 Suppl):S121–8. 20Greenland S PJ, Robins JM. Causal diagrams for epidemiologic research. Epidemiology. 1999;10(1):37-48. 21Hernán MA H-DS, Robins JM.A structural approach to selection bias. Epidemiology 2004;15(5):615-25. 22Lim Choi Keung SN, Ogunsina I, Rossiter J, Langford G, Tyler E, Arvanitis TN. Standardised representation of healthcare information in secondary care research: A Central England Case Study. Stud Health Technol Inform. 2012;180:529-33.

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23Institute of Electrical and Electronics Engineers. IEEE Standard Computer Dictionary: A Compilation of IEEE Standard Computer Glossaries. New York, NY: 1990. 24 O'Brien J, Marakas G. Introduction to Information Systems, McGraw-Hill/Irwin; 13 edition 25Park YR, Kim JH. Achieving interoperability for metadata registries using comparative object modeling. Stud Health Technol Inform. 2010;160(Pt 2) 26EN 13606 Association, CEN/ISO 13606 standard - Semantic interoperability, http://www.en13606.org/the-ceniso-en13606-standard/semantic-interoperability, accessed on 14.06.2013. 27EN 13606 Association, CEN/ISO 13606 standard - Semantic interoperability, http://www.en13606.org/the-ceniso-en13606-standard/semantic-interoperability, accessed on 14.06.2013. 28Park YR, Kim H, An EY, Kim HH, Kim JH, Park RW, Park DK, Jung EY, Kim JH. Establishing semantic interoperability in the course of clinical document exchange using international standard for metadata registry. J Korean Med Assoc. 2012;55(8):729-40. 29Lim S, Seo T, Lee C, Shin S. Study on the international standardization for the semantic metadata mapping procedure. Busan 2012; 243-9 30http://www.w3.org/2005/Incubator/lld/XGR-lld-vocabdataset-20111025/ 31Blanchi C, Petrone J. Distributed Interoperable Metadata Registry. D-Lib Magazine, 2001:7(12)http://www.dlib.org/dlib/december01/blanchi/12blanchi.html 32National Information Standards Organization (NISO) (), A Framework of Guidance for Building Good Digital Collections, 3rd ed., 2007. A NISO Recommended Practice, Baltimore, USA 33National Information Standards Organization (NISO), Understanding Metadata. NISO Press. http://www.niso.org/publications/press/UnderstandingMetadata.pdf 34 Duval E. Metadata Standards, What, Who & Why, Journal of Universal Computer Science, 2001;7(7):591-601, Springer 35 Cabinet Office, e-Government Metadata Standard Version 3.1, 2005, e-Government Unit, London 36 De Carvalho Moura A, Machado Campos M, Barreto C. A survey on metadata for describing and retrieving Internet resources, World Wide Web, 1998;1(4):221-40, Kluwer Academic Publishers 37Bagley P. (Nov), Extension of programming language concepts, 1968. Philadelphia: University City Science Center 38Solntseff N, Yezerski A, A survey of extensible programming languages, Annual Review in Automatic Programming, Elsevier Science Ltd, 1974;7:267–307 39Lambe P. Organising Knowledge: Taxonomies, Knowledge and Organisational effectiveness, 2007, Chandos Publishing, Oxford 40 National Information Standards Organization (NISO), Understanding Metadata, NISO Press, 2004, Bethesda, USA 41 National Information Standards Organization (NISO), A Framework of Guidance for Building Good Digital Collections, 3rd ed., 2007. A NISO Recommended Practice, NISO, Baltimore, USA 42Hüner K, Otto B, Österle H. Collaborative management of business metadata, in: International Journal of Information Management, 2011 43Ngouongo SM, Löbe M, Stausberg J. The ISO/IEC 11179 norm for metadata registries: Does it cover healthcare standards in empirical research? J Biomed Inform. 2012 Dec 14.

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44Li JH, Gao JX, Dong JN, Wu W, Hou YF. A metadata registry for metadata interoperability. Data Science Journal. 2007;6(SUPPL.):S379-S84 45King T, Merka J, Narock T, Walker R, Bargatze L. A registry framework and Rosetta attributes for distributed science. Earth Science Informatics, 2010;3(1-2):127-33 46Polydoratou P, Nicholas D. Familiarity with and use of metadata formats and metadata registries amongst those working in diverse professional communities within the information sector, Aslib Proceedings, 2001;53(8):309-24 47 International Organization for Standardization and the International Electromechanical Commission (ISO/IEC) (2003), Information Technology - Metadata Registries - Part 3: Registry metamodel and basic attributes, ISO/IEC 11179-3:2003(E), International Organization for Standardization, Geneva 48http://dublincore.org/documents/dces/ 49http://www.ietf.org/rfc/rfc5013.txt 50http://www.iso.org/iso/iso_catalogue/catalogue_ics/catalogue_detail_ics.htm?csnumber=52142 51http://www.niso.org/kst/reports/standards?step=2&gid=None&project_key=9b7bffcd2daeca6198b4ee5a848f9beec2f600e5 52http://microformats.org/ 53http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=38854 54Ruggieri AP, Elkin P, Chute CG. Representation by standard terminologies of health status concepts contained in two health status assessment instruments used in rheumatic disease management. Proc AMIA Symp. 2000:734–8. 55http://www.niso.org/standards/z39-85-2007/ 56http://microformats.org 57http://www.cms.gov/Regulations-and-Guidance/HIPAA-Administrative-Simplification/HIPAAGenInfo/index.html?redirect=/HIPAAGenInfo/ 58http://www.informationweek.com/healthcare/policy/it-executives-reject-meaningful-use-meta/231602114 59http://www.informationweek.com/healthcare/policy/it-executives-reject-meaningful-use-meta/231602114 60Liu D, Wang X, Pan F, Yang P, Xu Y, Tang X, Hu J, Rao K. Harmonization of health data at national level: a pilot study in China. Int J Med Inform. 2010 Jun;79(6):450-8. 61Liu D, Wang X, Pan F, Yang P, Xu Y, Tang X, Hu J, Rao K. Harmonization of health data at national level: a pilot study in China. Int J Med Inform. 2010 Jun;79(6):450-8. 62http://prism.epi.usf.edu/prism/ 63http://www.ihtsdo.org/snomed-ct/ 64Thompson J Q&A: What Is a Registry/Repository, and Who Should Consider One? 2007. http://www.gartner.com/it/content/754400/754413/qa_what_is_a_registry.pdf 65http://nesipublic.spawar.navy.mil/nesix/perspectives/P1050.html 66Marco D, Jennings M. Universal Metadata Models. Wiley, 2004. Chapter 2 67Marco D, Jennings M. Universal Metadata Models. Wiley, 2004. Chapter 2 68Moss LT, Atre S. Business Intelligence Roadmap: The Complete Project Lifecycle for Decision-Support Applications. Addison-Wesley Professional, 2003. 69http://meteor.aihw.gov.au/content/index.phtml/itemId/181414 70http://www.outcome.com/ropr.htm 71http://www.naaccr.org 72http://www.corrona.org

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73Ohman EM, Bhatt DL, Steg PG, Goto S, Hirsch AT, Liau CS, Mas JL, Richard AJ, Röther J, Wilson PW; REACH Registry Investigators. The Reduction of Atherothrombosis for Continued Health (REACH) Registry: an international, prospective, observational investigation in subjects at risk for atherothrombotic events - study design. Am Heart J. 2006;151(4):786.e1-10 74Reid CM, Ademi Z, Nelson MR, Connor G, Chew DP, Shiel L, Smeath A, De Looze F, Steg PhG, Bhatt DL and Liew D. Outcomes from the REACH Registry for Australian general practice patients with or at high risk of atherothrombosis. Med J Aust 2012;196(3):193-7. 75http://www.reachregistry.org 76http://ichom.org/#&panel1-3 77http://www.med.monash.edu.au/sphpm/creps/index.html 78http://www.ispor.org/news/articles/dec05/Patient_registries.asp 79http://www.who.int/ictrp/publications/en 80http://www.ihe.net 81http://www.phdsc.org 82www.i2b2.org 83Natter MD, Quan J, Ortiz DM, Bousvaros A, Ilowite NT, Inman CJ, Marsolo K, McMurry AJ, Sandborg CI, Schanberg LE, Wallace CA, Warren RW, Weber GM, Mandl KD, An i2b2-based, generalizable, open source, self-scaling chronic disease registry, J Am Med Inform Assoc. 2013 Jan 1;20(1):172-9. doi: 10.1136/amiajnl-2012-001042. Epub 2012 Jun 25. 84http://www.eubirod.eu/index.html 85DiIorio CT, Carinci F, Azzopardi J, Baglioni V, Beck P, Cunningham S, Evripidou A, Leese G, Loevaas KF, Olympios G, Federici MO, Pruna S, Palladino P, Skeie S, Taverner P, Traynor V, Benedetti MM. Privacy impact assessment in the design of transnational public health information systems: the BIRO project, J Med Ethics. 2009 Dec;35(12):753-61. 86 Di Iorio CT, Carinci F, Brillante M, Azzopardi J, Beck P, BratinaN, Cunningham SG, De Beaufort C, Debacker N, Jarosz-Chobot P, Jecht M, Lindblad U, Moulton T, Metelko Z, Nagy A, Olympios G, Pruna S, Røder M, Skeie S, Storms F, Massi Benedetti M. Cross-border flow of health information: is 'privacy by design' enough? Privacy performance assessment in EUBIROD.Eur J Public Health. 2012 May 4. 87http://www.cuore.iss.it/eurociss/en/project/project.asp 88http://www.emsp.org/ 89http://www.epirare.eu/ 90http://www.ear.efort.org 91http://www.eurahs.eu/ 92http://www.treat-nmd.eu/resources/patient-registries/registries-toolkit 93Bruder O, Schneider S, Nothnagel D, Dill T, Hombach V, Schulz-Menger J, Nagel E, Lombardi M, van Rossum AC, Wagner A, Schwitter J, Senges J, Sabin GV, Sechtem U, Mahrholdt H. EuroCMR (European Cardiovascular Magnetic Resonance) registry: results of the German pilot phase. J Am Coll Cardiol. 2009;54(15):1457-66 94http://www.eurocmr-registry.com/layout/index2.php 95http://www.eaaci.org 96http://www.escardio.org/guidelines-surveys/eorp/surveys/chronic-ischaemic-cardiovacsular-disease/Pages/cicd-pilot-registry.aspx 97http://www.escardio.org/guidelines-surveys/eorp/surveys/chronic-ischaemic-cardiovacsular-disease/Pages/cicd-pilot-registry.aspx 98http://ec.europa.eu/health/strategy/implementation/hic/index_en.htm 99http://www.euro.centre.org

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100http://ec.europa.eu/digital-agenda/en/digital-life/health 101http://www.epsos.eu 102http://eudragmp.ema.europa.eu/inspections/displayWelcome.do;jsessionid=ac10292bd31811528e45a7943b49e21bfcd21d8791f.rlmNb3aInljyqA4IpR9BcxaNbNq 103http://www.eunethta.eu 104http://eudrapharm.eu/eudrapharm 105http://www.burqol-rd.com 106http://www.hiqa.ie 107http://www.hiqa.ie/publications/international-review-health-information-sources 108http://www.salusproject.eu/