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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JMI</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Med Inform</journal-id>
      <journal-title>JMIR Medical Informatics</journal-title>
      <issn pub-type="epub">2291-9694</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v12i1e52967</article-id>
      <article-id pub-id-type="pmid">38354027</article-id>
      <article-id pub-id-type="doi">10.2196/52967</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Review</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Use of Metadata-Driven Approaches for Data Harmonization in the Medical Domain: Scoping Review</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Lovis</surname>
            <given-names>Christian</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Löbe</surname>
            <given-names>Matthias</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Xu</surname>
            <given-names>Wei</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Peng</surname>
            <given-names>Yuan</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Institute for Medical Informatics and Biometry</institution>
            <institution>Carl Gustav Carus Faculty of Medicine</institution>
            <institution>Technische Universität Dresden</institution>
            <addr-line>Fetscherstraße 74</addr-line>
            <addr-line>Dresden, 01307</addr-line>
            <country>Germany</country>
            <fax>49 3514585738</fax>
            <phone>49 3514583648</phone>
            <email>yuan.peng@tu-dresden.de</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-6163-9532</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Bathelt</surname>
            <given-names>Franziska</given-names>
          </name>
          <degrees>Dr Rer Nat</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-4139-5489</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Gebler</surname>
            <given-names>Richard</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0009-0004-1543-9769</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Gött</surname>
            <given-names>Robert</given-names>
          </name>
          <degrees>Dipl.-Ing.</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9985-8311</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author">
          <name name-style="western">
            <surname>Heidenreich</surname>
            <given-names>Andreas</given-names>
          </name>
          <degrees>Dipl.-Biol., Dr Rer Nat</degrees>
          <xref rid="aff4" ref-type="aff">4</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-2650-4464</ext-link>
        </contrib>
        <contrib id="contrib6" contrib-type="author">
          <name name-style="western">
            <surname>Henke</surname>
            <given-names>Elisa</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-5002-2676</ext-link>
        </contrib>
        <contrib id="contrib7" contrib-type="author">
          <name name-style="western">
            <surname>Kadioglu</surname>
            <given-names>Dennis</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff4" ref-type="aff">4</xref>
          <xref rid="aff5" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1561-4924</ext-link>
        </contrib>
        <contrib id="contrib8" contrib-type="author">
          <name name-style="western">
            <surname>Lorenz</surname>
            <given-names>Stephan</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-9152-1826</ext-link>
        </contrib>
        <contrib id="contrib9" contrib-type="author">
          <name name-style="western">
            <surname>Vengadeswaran</surname>
            <given-names>Abishaa</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff5" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0009-0005-1077-1698</ext-link>
        </contrib>
        <contrib id="contrib10" contrib-type="author">
          <name name-style="western">
            <surname>Sedlmayr</surname>
            <given-names>Martin</given-names>
          </name>
          <degrees>Dr Rer Nat, Prof Dr</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-9888-8460</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Institute for Medical Informatics and Biometry</institution>
        <institution>Carl Gustav Carus Faculty of Medicine</institution>
        <institution>Technische Universität Dresden</institution>
        <addr-line>Dresden</addr-line>
        <country>Germany</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Thiem-Research GmbH</institution>
        <addr-line>Cottbus</addr-line>
        <country>Germany</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Core Unit Datenintegrationszentrum</institution>
        <institution>University Medicine Greifswald</institution>
        <addr-line>Greifswald</addr-line>
        <country>Germany</country>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution>Department for Information and Communication Technology (DICT), Data Integration Center (DIC)</institution>
        <institution>Goethe University Frankfurt, University Hospital</institution>
        <addr-line>Frankfurt am Main</addr-line>
        <country>Germany</country>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution>Institute for Medical Informatics</institution>
        <institution>Goethe University Frankfurt, University Hospital Frankfurt</institution>
        <addr-line>Frankfurt am Main</addr-line>
        <country>Germany</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Yuan Peng <email>yuan.peng@tu-dresden.de</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2024</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>14</day>
        <month>2</month>
        <year>2024</year>
      </pub-date>
      <volume>12</volume>
      <elocation-id>e52967</elocation-id>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>9</month>
          <year>2023</year>
        </date>
        <date date-type="rev-request">
          <day>24</day>
          <month>10</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>1</day>
          <month>12</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>3</day>
          <month>12</month>
          <year>2023</year>
        </date>
      </history>
      <copyright-statement>©Yuan Peng, Franziska Bathelt, Richard Gebler, Robert Gött, Andreas Heidenreich, Elisa Henke, Dennis Kadioglu, Stephan Lorenz, Abishaa Vengadeswaran, Martin Sedlmayr. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 14.02.2024.</copyright-statement>
      <copyright-year>2024</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Medical Informatics, is properly cited. The complete bibliographic information, a link to the original publication on https://medinform.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://medinform.jmir.org/2024/1/e52967" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Multisite clinical studies are increasingly using real-world data to gain real-world evidence. However, due to the heterogeneity of source data, it is difficult to analyze such data in a unified way across clinics. Therefore, the implementation of Extract-Transform-Load (ETL) or Extract-Load-Transform (ELT) processes for harmonizing local health data is necessary, in order to guarantee the data quality for research. However, the development of such processes is time-consuming and unsustainable. A promising way to ease this is the generalization of ETL/ELT processes.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>In this work, we investigate existing possibilities for the development of generic ETL/ELT processes. Particularly, we focus on approaches with low development complexity by using descriptive metadata and structural metadata.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>We conducted a literature review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We used 4 publication databases (ie, PubMed, IEEE Explore, Web of Science, and Biomed Center) to search for relevant publications from 2012 to 2022. The PRISMA flow was then visualized using an R-based tool (Evidence Synthesis Hackathon). All relevant contents of the publications were extracted into a spreadsheet for further analysis and visualization.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Regarding the PRISMA guidelines, we included 33 publications in this literature review. All included publications were categorized into 7 different focus groups (ie, medicine, data warehouse, big data, industry, geoinformatics, archaeology, and military). Based on the extracted data, ontology-based and rule-based approaches were the 2 most used approaches in different thematic categories. Different approaches and tools were chosen to achieve different purposes within the use cases.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Our literature review shows that using metadata-driven (MDD) approaches to develop an ETL/ELT process can serve different purposes in different thematic categories. The results show that it is promising to implement an ETL/ELT process by applying MDD approach to automate the data transformation from Fast Healthcare Interoperability Resources to Observational Medical Outcomes Partnership Common Data Model. However, the determining of an appropriate MDD approach and tool to implement such an ETL/ELT process remains a challenge. This is due to the lack of comprehensive insight into the characterizations of the MDD approaches presented in this study. Therefore, our next step is to evaluate the MDD approaches presented in this study and to determine the most appropriate MDD approaches and the way to integrate them into the ETL/ELT process. This could verify the ability of using MDD approaches to generalize the ETL process for harmonizing medical data.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>ETL</kwd>
        <kwd>ELT</kwd>
        <kwd>Extract-Load-Transform</kwd>
        <kwd>Extract-Transform-Load</kwd>
        <kwd>interoperability</kwd>
        <kwd>metadata-driven</kwd>
        <kwd>medical domain</kwd>
        <kwd>data harmonization</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>Multisite clinical studies are increasingly using real-world data to gain real-world evidence, especially during the COVID-19 pandemic [<xref ref-type="bibr" rid="ref1">1</xref>]. However, not all clinics use the same hospital information system, resulting in heterogeneity of data produced by different hospital information systems. These heterogeneous data are not semantically and syntactically interoperable. Therefore, it is difficult to analyze such data in a unified way across sites. For this, the heterogeneous data need to be harmonized and standardized, for example, by using a common data model (CDM) [<xref ref-type="bibr" rid="ref2">2</xref>]. For example, the European Medical Agency [<xref ref-type="bibr" rid="ref3">3</xref>] set up the DARWIN EU (Data Analysis and Real World Interrogation Network European Union) [<xref ref-type="bibr" rid="ref4">4</xref>] to provide real-world evidence on use and adverse events of medicines across the European Union. DARWIN EU uses the Observational Medical Outcomes Partnership (OMOP) CDM [<xref ref-type="bibr" rid="ref5">5</xref>] as the base model, which is provided by the Observational Health Data Sciences and Informatics [<xref ref-type="bibr" rid="ref6">6</xref>] community. To participate in such networks, a transformation of local data is needed. A common approach is to develop an Extract-Transform-Load (ETL) or Extract-Load-Transform (ELT) process. Both are used to harmonize heterogeneous data into the target systems. The only difference between them is the order of processing data. ETL transforms the data before loading them into the target systems, while ELT loads the data into the target systems first, and then transforms the data. Due to the different data formats and source systems, multiple ETL/ELT processes have to be implemented [<xref ref-type="bibr" rid="ref7">7</xref>-<xref ref-type="bibr" rid="ref10">10</xref>]. This work is time-consuming and hard to maintain [<xref ref-type="bibr" rid="ref11">11</xref>].</p>
      <p>Using a standard data exchange format can reduce the complexity of transforming heterogeneous data into CDMs. An example is the Fast Healthcare Interoperability Resources (FHIR) [<xref ref-type="bibr" rid="ref12">12</xref>] format. FHIR is a communication standard and is provided by the Health Level 7 (HL7) [<xref ref-type="bibr" rid="ref13">13</xref>]. In Germany, the Medical Informatics Initiative (MII) [<xref ref-type="bibr" rid="ref14">14</xref>] provides a Core Data Set (CDS) [<xref ref-type="bibr" rid="ref15">15</xref>] in FHIR format for enabling the interoperability of data across all university hospitals. Another German association “the National Association of Statutory Health Insurance Physicians” (KBV, German: Kassenärztliche Bundesvereinigung) [<xref ref-type="bibr" rid="ref16">16</xref>] also provides a KBV CDS in FHIR format, which provides a stable foundation for the development of the medical information objects [<xref ref-type="bibr" rid="ref17">17</xref>] (eg, immunization records and maternity records). Although both MII CDS and KBV CDS are based on the German HL7 Basis Profiles [<xref ref-type="bibr" rid="ref18">18</xref>], the FHIR profiles defined in the 2 CDSs are not identical [<xref ref-type="bibr" rid="ref19">19</xref>]. This is due to the different requirements of MII and KBV. For example, codes indicating departments within a clinic (eg, 0100 for internal medicine department) are defined in different value-sets and therefore use different coding systems. This also complicates the implementation and maintenance of ETL/ELT processes.</p>
      <p>Furthermore, most countries try to standardize their electronic health records (EHR) data for research and to improve the interoperability of the data. Consequently, country-specific FHIR profiles are developed, for example, German HL7 Basis Profiles [<xref ref-type="bibr" rid="ref18">18</xref>] and the US CDS [<xref ref-type="bibr" rid="ref20">20</xref>]. Due to different languages (ie, German vs English), different structure definitions (eg, extensions and cardinality) and different coding systems (eg, system URL for International Classification of Diseases, 10, Revision: German Modification [<xref ref-type="bibr" rid="ref21">21</xref>] vs system URL for International Classification of Diseases, 10, Clinical Modification [<xref ref-type="bibr" rid="ref22">22</xref>]) used in the FHIR profiles, different ETL processes need to be implemented [<xref ref-type="bibr" rid="ref8">8</xref>,<xref ref-type="bibr" rid="ref23">23</xref>]. Although these are just a few examples, it is conceivable that with the expansion of supported use cases, the time required for implementing an ETL/ELT process increases massively, while the maintainability decreases. Therefore, the implementation of a generic ETL/ELT process for harmonizing local health data can guarantee the semantic and syntactic interoperability of research data across sites and countries.</p>
      <p>Using metadata for the implementation of ETL/ELT processes is a promising approach, as stated by David Loshin [<xref ref-type="bibr" rid="ref24">24</xref>]: “in order to organize data for analytical purposes, it will need to be extracted from the original source (source metadata), transformed into a representation that is consistent with the warehouse (target metadata) in a way that does not lose information due to differences in format and precision (structure metadata) and is aligned in a meaningful way (semantic metadata).” A very broad definition of metadata is “data about other data” [<xref ref-type="bibr" rid="ref25">25</xref>]. Depending on the specific context of use, metadata can be classified into 3 types [<xref ref-type="bibr" rid="ref26">26</xref>]:</p>
      <list list-type="bullet">
        <list-item>
          <p><bold>Descriptive metadata</bold>: the metadata is used for discovery and identification purposes, for example metadata for source and target data.</p>
        </list-item>
        <list-item>
          <p><bold>Structural metadata</bold>: the metadata is used for managing data in information systems, for example, column names and table names in a database.</p>
        </list-item>
        <list-item>
          <p><bold>Administrative metadata</bold>: the metadata exists within a database that provides additional information, for example, the name of a person, who has changed the data in a database.</p>
        </list-item>
      </list>
      <p>Metadata can be represented by metadata languages (eg, Resource Description Framework and Notation3) [<xref ref-type="bibr" rid="ref27">27</xref>]. Such languages are also called ontology languages. For enabling the interoperability of data from different source and target systems, rule languages (eg, Rule Markup Language and Semantic Web Rule Language) can be used to define the transformation rules between them [<xref ref-type="bibr" rid="ref27">27</xref>]. Therefore, the use of metadata is expected to improve the development and maintenance for transforming FHIR resources to OMOP CDM.</p>
      <p>As a side note, we understand any (descriptive and structural) metadata-based approach used for developing ETL/ELT processes as metadata-driven (MDD) approach. This work focuses on providing an overview of the types of MDD approaches and their use in different thematic categories. The overview aims to identify a suitable MDD approach to enhance the data transformation from FHIR to OMOP CDM. This will be achieved by answering the following questions:</p>
      <list list-type="bullet">
        <list-item>
          <p>Q1: What are the themes of application for MDD approaches?</p>
        </list-item>
        <list-item>
          <p>Q2: What types of MDD approaches exist in the literature?</p>
        </list-item>
        <list-item>
          <p>Q3: What are the reasons for the usage of MDD approaches?</p>
        </list-item>
        <list-item>
          <p>Q4: What tool was used to implement the MDD approach?</p>
        </list-item>
      </list>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>To answer our 4 research questions, we conducted a literature review. To ensure the transparency of the review process, we followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [<xref ref-type="bibr" rid="ref28">28</xref>]. We used 4 publication databases (ie, PubMed, IEEE Explore, Web of Science, and Biomed Center) to search for relevant publications from 2012 to 2022 written in German or English (<xref ref-type="boxed-text" rid="box1">Textbox 1</xref>). The first search was performed on August 11, 2022, and the second one was on March 15, 2023, which in turn completed the search through December 31, 2022. The collected publications were loaded into the Zotero Citation Management program (Corporation for Digital Scholarship) [<xref ref-type="bibr" rid="ref29">29</xref>] and the duplicates were manually removed. To better categorize the publications to be excluded, we defined 8 exclusion criteria (<xref ref-type="boxed-text" rid="box2">Textbox 2</xref>).</p>
      <p>This review was a 2-fold process consisting of Title-Abstract-Screening (TAS) and full-text screening (FTS). Both screening processes used the same exclusion criteria listed in <xref ref-type="boxed-text" rid="box2">Textbox 2</xref>. The unique publications were divided into 2 groups based on their publication dates and uploaded to a research collaboration platform, Rayyan (Qatar Computing Research Institute and Cochrane Bahrain) [<xref ref-type="bibr" rid="ref30">30</xref>], as 2 separate projects. Each publication group was assigned with 4 reviewers. The corresponding author reviewed all publications. The TAS was performed under the blind-modus, so that each reviewer could label the publication independently. The blind-modus was turned off after all publications were tagged and the conflicts were discussed and resolved. After that, all included publications were randomly divided into 2 groups and reloaded into Rayyan as a new project for FTS. Similar to TAS, 4 reviewers were assigned to each publication group and the corresponding author reviewed all publications. The FTS was also conducted under the blind-modus and followed the same review process as the TAS.</p>
      <p>We extracted the content of all included publications based on the categories listed in <xref ref-type="boxed-text" rid="box3">Textbox 3</xref>. The extraction of publication content was done by the corresponding author and validated by 4 coauthors. The extracted content was stored in a spreadsheet for further analysis and visualization.</p>
      <p>The result of the literature review was visualized using an R-based tool, which was developed based on PRISMA 2020 [<xref ref-type="bibr" rid="ref31">31</xref>].</p>
      <boxed-text id="box1" position="float">
        <title>Search string and publication databases.</title>
        <p>Search string</p>
        <p>
          <bold>PubMed</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>((meta data) OR (meta-data) OR (metadata) OR (ontology) OR (rules)) AND ((extract transform load) OR (ETL) OR (extract load transform) OR (ELT))</p>
          </list-item>
        </list>
        <p>
          <bold>IEEE Explore</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>((“All Metadata”:metadata) OR (“All Metadata”:meta-data) OR (“All Metadata”:meta data) OR (“All Metadata”:ontology) OR (“All Metadata”:rules)) AND ((“All Metadata”:ETL) OR (“All Metadata”:extract transform load) OR (“All Metadata”:ELT) OR (“All Metadata”:extract load transform))</p>
          </list-item>
        </list>
        <p>
          <bold>Web of Science</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>(ALL=(metadata) OR ALL=(meta-data) OR ALL=(“meta data”) OR ALL=(ontology) OR ALL=(rules)) AND (ALL=(ETL) OR ALL=(“extract transform load”) OR ALL=(ELT) OR ALL=(“extract load transform”))</p>
          </list-item>
        </list>
        <p>
          <bold>Biomed Center (BMC)</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>(“meta data” OR meta-data OR metadata OR ontology OR rules) AND (“extract transform load” OR ETL OR “extract load transform” OR ELT)</p>
          </list-item>
        </list>
      </boxed-text>
      <boxed-text id="box2" position="float">
        <title>Labels and descriptions of exclusion criteria.</title>
        <p>
          <bold>Wrong_abbreviation</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication does not contain Extract-Transform-Load (ETL) as “Extract-Transform-Load.”</p>
          </list-item>
          <list-item>
            <p>Publication does not contain Extract-Load-Transform (ELT) as “Extract-Load-Transform.”</p>
          </list-item>
        </list>
        <p>
          <bold>Wrong_definition</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication does not use metadata in the context of “metadata of data in source or target.”</p>
          </list-item>
          <list-item>
            <p>Publication does not use rules in the context of “rules for data transformation.”</p>
          </list-item>
        </list>
        <p>
          <bold>Only_etl_elt</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication describes only ETL/ELT.</p>
          </list-item>
        </list>
        <p>
          <bold>Only_metadata</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication describes only metadata.</p>
          </list-item>
        </list>
        <p>
          <bold>Wrong_focus</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication mentioned metadata and ETL/ELT, but the focus is not about data harmonization</p>
          </list-item>
        </list>
        <p>
          <bold>Wrong_type</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication is not a conference paper or a journal publication</p>
          </list-item>
        </list>
        <p>
          <bold>Foreign_language</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication is written in other languages than English and German</p>
          </list-item>
        </list>
        <p>
          <bold>Wrong_content</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Publication does not mention ETL/ELT or metadata</p>
          </list-item>
        </list>
      </boxed-text>
      <boxed-text id="box3" position="float">
        <title>Categories for data extraction.</title>
        <p>
          <bold>Theme</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>The main theme of the work.</p>
          </list-item>
        </list>
        <p>
          <bold>Metadata-driven method</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>The used metadata-driven method in the work.</p>
          </list-item>
        </list>
        <p>
          <bold>Metadata-driven method tool</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>Tool which was used to conduct the metadata-driven method.</p>
          </list-item>
        </list>
        <p>
          <bold>Purpose</bold>
        </p>
        <list list-type="bullet">
          <list-item>
            <p>The purpose of using the metadata-driven method.</p>
          </list-item>
        </list>
      </boxed-text>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Literature Search</title>
        <p>The literature search resulted in 538 publications. After removing 85 duplicates, 453 publications were screened during the TAS phase. By using the exclusion criteria defined in <xref ref-type="boxed-text" rid="box2">Textbox 2</xref> and excluding the publications, which have no full-text, 64 publications were included for FTS. Finally, we included 33 publications in this work. The screening process and results are structured using the PRISMA flow diagram 2020 (<xref rid="figure1" ref-type="fig">Figure 1</xref>). A complete list of included publications is available in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>.</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. Generated using an R-based tool (reproduced from Haddaway et al [<xref ref-type="bibr" rid="ref31">31</xref>], with permission from Neal R Haddaway).</p>
          </caption>
          <graphic xlink:href="medinform_v12i1e52967_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Distribution of Publications</title>
        <p>In order to gain an overview of the potential application focuses of MDDs (Q1) and thus an indication of where the approaches have proven beneficial, the focused theme of application was first evaluated. According to the extracted data, the focuses of all included publications are classified into 7 different categories, namely medicine (n=9) [<xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref39">39</xref>], data warehouse (n=13) [<xref ref-type="bibr" rid="ref40">40</xref>-<xref ref-type="bibr" rid="ref52">52</xref>], big data (n=4) [<xref ref-type="bibr" rid="ref53">53</xref>-<xref ref-type="bibr" rid="ref56">56</xref>], industry (n=4) [<xref ref-type="bibr" rid="ref57">57</xref>-<xref ref-type="bibr" rid="ref60">60</xref>], geoinformatics (n=1) [<xref ref-type="bibr" rid="ref61">61</xref>], archaeology (n=1) [<xref ref-type="bibr" rid="ref62">62</xref>], and military (n=1) [<xref ref-type="bibr" rid="ref63">63</xref>]. This shows that data warehouse and medicine are the 2 categories that use the MDD approach the most.</p>
      </sec>
      <sec>
        <title>MDD Approaches Used for Various Thematic Categories</title>
        <p>Different types of MDD approaches were used across the thematic categories. To gain knowledge about the use of these types of MDD approaches in each category (Q2), the distribution of MDD approaches was investigated. <xref rid="figure2" ref-type="fig">Figure 2</xref> shows the application of different types of MDD approaches in different thematic categories. The most frequently used type of MDD approach was ontology-based, where the ontology (using for example, resource description framework) of the source or target was applied in the ETL/ELT process. This approach was used in 6 categories, particularly in the categories of data warehouse [<xref ref-type="bibr" rid="ref45">45</xref>-<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref52">52</xref>] and medicine [<xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref37">37</xref>-<xref ref-type="bibr" rid="ref39">39</xref>]. Another frequently used type of MDD approach was rule-based, which applied transformation rules generated based on the source and target to the ETL/ELT process. The rule-based approach was also widely used in the categories of data warehouse [<xref ref-type="bibr" rid="ref40">40</xref>-<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] and medicine [<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref39">39</xref>]. All other MDD approaches besides the ontology-based and rule-based approaches were categorized as “other” (<xref ref-type="table" rid="table1">Table 1</xref>).</p>
        <fig id="figure2" position="float">
          <label>Figure 2</label>
          <caption>
            <p>Metadata-driven approaches used in each thematic category.</p>
          </caption>
          <graphic xlink:href="medinform_v12i1e52967_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
        <table-wrap position="float" id="table1">
          <label>Table 1</label>
          <caption>
            <p>MDD<sup>a</sup> approaches that are categorized as “other.”</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="220"/>
            <col width="750"/>
            <thead>
              <tr valign="top">
                <td colspan="2">MDD approach type and publication</td>
                <td>Example</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="3">
                  <bold>UML<sup>b</sup>-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Dhaouadi et al [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>UML class diagram is used for modeling the transformation process</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>Graphic-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Dhaouadi et al [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>BPMN<sup>c</sup> standard is used for modeling an ETL<sup>d</sup> process</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>Ad hoc formalisms-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Dhaouadi et al [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>Entity Mapping Diagram is used for representing ETL tasks</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>MDA<sup>e</sup>-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Dhaouadi et al [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>MDA is a multilayered framework with multiple submodules for separation of the specification of a functionality from its implementation</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>Message-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Novak et al [<xref ref-type="bibr" rid="ref51">51</xref>]</td>
                <td>“Normal message” contains information of mapping and transformation; “command message” configures the (execution) system</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>Template-based</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>McCarthy et al [<xref ref-type="bibr" rid="ref58">58</xref>]</td>
                <td>A transformation template for each data source that manages the complex transformation process</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Binding et al [<xref ref-type="bibr" rid="ref62">62</xref>]</td>
                <td>A template contains the mapping patterns which is then used for querying in database</td>
              </tr>
              <tr valign="top">
                <td colspan="3">
                  <bold>Metadata-based<sup>f</sup></bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Ozyurt and Grethe [<xref ref-type="bibr" rid="ref36">36</xref>]</td>
                <td>Implementing a generic data transformation language to transform heterogeneous data from multiple sources to a common format</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Tomingas et al [<xref ref-type="bibr" rid="ref44">44</xref>]</td>
                <td>Metadata of the source and target stored in a knowledge and metadata repository</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Suleykin and Panfilov [<xref ref-type="bibr" rid="ref60">60</xref>]</td>
                <td>Metadata of the mapping path stored in a metadata management framework</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table1fn1">
              <p><sup>a</sup>MDD: metadata-driven.</p>
            </fn>
            <fn id="table1fn2">
              <p><sup>b</sup>UML: unified modeling language.</p>
            </fn>
            <fn id="table1fn3">
              <p><sup>c</sup>BPMN: Business Process Model Notation.</p>
            </fn>
            <fn id="table1fn4">
              <p><sup>d</sup>ETL: Extract-Transform-Load.</p>
            </fn>
            <fn id="table1fn5">
              <p><sup>e</sup>MDA: Model Driven Architecture.</p>
            </fn>
            <fn id="table1fn6">
              <p><sup>f</sup>Metadata-based approach: approach uses metadata without any specification.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Purposes of Using MDD Method for Data Harmonization</title>
        <p>The purpose of using MDD approaches in each use case was then investigated to clarify the reasons why MDD approaches were used (Q3). <xref rid="figure3" ref-type="fig">Figure 3</xref> shows different purposes of using MDD approaches in developing ETL/ELT processes based on the extracted data. The majority of publications describe the use of MDD approaches to develop an ETL/ELT process. This purpose can be divided into three detailed categories: (1) to automate the development of the ETL/ELT process [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref48">48</xref>-<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref60">60</xref>], (2) to develop a generic ETL/ELT process [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref52">52</xref>], and (3) to develop a new ETL/ELT process without any further technical specifications [<xref ref-type="bibr" rid="ref40">40</xref>,<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref61">61</xref>]. Additionally, the transformation part of the ETL/ELT process could also be automated by applying an MDD approach [<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref63">63</xref>]. For example, Chen and Zhao [<xref ref-type="bibr" rid="ref41">41</xref>] described an MDD approach for the automatic generation of SQL scripts for data transformation. Moreover, using MDD approaches can also help to improve the performance of ETL/ELT processes [<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref46">46</xref>] or to partially or fully reuse the ETL/ELT process [<xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref62">62</xref>]. Other goals (categorized as “Others” in <xref rid="figure3" ref-type="fig">Figure 3</xref>), such as simplifying the maintenance of the transformation process [<xref ref-type="bibr" rid="ref37">37</xref>] and reducing the complexity of the extraction process [<xref ref-type="bibr" rid="ref53">53</xref>], can also be realized by using MDD approaches in ETL/ELT processes.</p>
        <fig id="figure3" position="float">
          <label>Figure 3</label>
          <caption>
            <p>Purposes of using MDD approaches in ETL/ELT process. ELT: Extract-Load-Transform; ETL: Extract-Transform-Load; i2b2: Informatics for Integrating Biology and the Bedside; MDD: metadata-driven.</p>
          </caption>
          <graphic xlink:href="medinform_v12i1e52967_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Relationship Between Use Case and Used MDD Approach</title>
        <p>As shown in the previous section, different MDD approaches were applied for different purposes. To further elucidate the reasons for choosing MDD approaches (Q3), the relationship between them was investigated. <xref ref-type="table" rid="table2">Table 2</xref> lists the number of publications, which used a type of MDD approach to achieve a specific purpose. The ontology-based approach was used to achieve purposes (1) and (2), and (4)-(7). For example, Huang et al [<xref ref-type="bibr" rid="ref63">63</xref>] created both local ontology (ontology based on the source data) and global ontology (ontology for the query processing) for the data transformation process, so that the data transformation from local ontology to global can be automated by applying ontology learning, ontology mapping, and ontology rules. Additionally, the ontology-based approach was also used to achieve other goals, such as controlling the ETL process to Informatics for Integrating Biology and the Bedside [<xref ref-type="bibr" rid="ref32">32</xref>] and reducing the complexity of the extraction process [<xref ref-type="bibr" rid="ref53">53</xref>]. Similar to the ontology-based approach, the rule-based approach was used to achieve the purposes of (1)-(3) and (5)-(7). Due to the reusability of the transformation rules, it was also possible to simplify the maintenance of the ETL/ELT process by applying rules in the process [<xref ref-type="bibr" rid="ref37">37</xref>]. Other MDD approaches such as template-based [<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref62">62</xref>], message-based [<xref ref-type="bibr" rid="ref51">51</xref>], and metadata-based [<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] were used to achieve the goals of (1)-(3) and (5)-(7). A metadata-based approach (eg, metadata management framework) can be used to develop the ETL tasks automatically [<xref ref-type="bibr" rid="ref60">60</xref>]. The detailed information of <xref ref-type="table" rid="table2">Table 2</xref> is available in the <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>.</p>
        <table-wrap position="float" id="table2">
          <label>Table 2</label>
          <caption>
            <p>Relationships between purposes and MDD<sup>a</sup> approaches used.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="70"/>
            <col width="460"/>
            <col width="180"/>
            <col width="160"/>
            <col width="130"/>
            <thead>
              <tr valign="top">
                <td colspan="2">Purposes</td>
                <td colspan="3">MDD approaches</td>
              </tr>
              <tr valign="top">
                <td>Number</td>
                <td>Description</td>
                <td>Ontology-based, n/N (%)</td>
                <td>Rule-based, n/N (%)</td>
                <td>Other, n/N (%)</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>(1)</td>
                <td>To automate the data transformation within an ETL<sup>b</sup>/ELT<sup>c</sup> process</td>
                <td>2/6 (33)</td>
                <td>3/6 (50)</td>
                <td>1/6 (17)</td>
              </tr>
              <tr valign="top">
                <td>(2)</td>
                <td>To reuse an ETL/ELT process (partially or completely)</td>
                <td>1/4 (25)</td>
                <td>2/4 (50)</td>
                <td>1/4 (25)</td>
              </tr>
              <tr valign="top">
                <td>(3)</td>
                <td>To improve the performance of an ETL/ELT process</td>
                <td>0/2 (0)</td>
                <td>1/2 (50)</td>
                <td>1/2 (50)</td>
              </tr>
              <tr valign="top">
                <td>(4)</td>
                <td>To develop a generic ETL/ELT process</td>
                <td>3/3 (100)</td>
                <td>0/3 (0)</td>
                <td>0/3 (0)</td>
              </tr>
              <tr valign="top">
                <td>(5)</td>
                <td>To develop an ETL/ELT process automatically</td>
                <td>5/9 (56)</td>
                <td>2/9 (22)</td>
                <td>2/9 (22)</td>
              </tr>
              <tr valign="top">
                <td>(6)</td>
                <td>To develop a new ETL/ELT process (without any other specific purposes)</td>
                <td>4/6 (67)</td>
                <td>1/6 (17)</td>
                <td>1/6 (17)</td>
              </tr>
              <tr valign="top">
                <td>(7)</td>
                <td>Other</td>
                <td>5/11 (45)</td>
                <td>2/11 (18)</td>
                <td>4/11 (36)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table2fn1">
              <p><sup>a</sup>MDD: metadata-driven<bold>.</bold></p>
            </fn>
            <fn id="table2fn2">
              <p><sup>b</sup>ETL: Extract-Transform-Load<bold>.</bold></p>
            </fn>
            <fn id="table2fn3">
              <p><sup>c</sup>ELT: Extract-Load-Transform<bold>.</bold></p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Tools Used for Implementing MDD Approaches</title>
        <p>Finally, we focused on the tools used to implemented MDD approaches (Q4). For achieving various purposes as shown in the previous section, different tools were used. As shown in <xref rid="figure4" ref-type="fig">Figure 4</xref>, each type of MDD approach can be implemented by using either an existing tool or a use case specific tool. Based on the included publications, the ontology-base approaches were mostly implemented using Protégé (Stanford Center for Biomedical Informatics Research) [<xref ref-type="bibr" rid="ref64">64</xref>]. Protégé is an ontology editor, as well as OntoEdit (Institute AIFB, University of Karlsruhe and Ontoprise GmbH) [<xref ref-type="bibr" rid="ref65">65</xref>]. The main reason for using an ontology editor is its ease of use and maintenance, as well as the various plug-ins. The use of case specific tools, such as ontology generator introduced by Kamil et al [<xref ref-type="bibr" rid="ref45">45</xref>], generated ontologies based on the data definition language of the relational database. Both types of tools were used for creating and maintaining the ontology, which was then used to establish a generic mapping logic in the ETL/ELT process [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref61">61</xref>]. Another type of frequently used MDD approach is rule-based, which is used for phrasing and storing the transformation rules. The transformation rules can be stored in a mapping sheet [<xref ref-type="bibr" rid="ref49">49</xref>], a CSV file [<xref ref-type="bibr" rid="ref34">34</xref>], a YAML (YAML Ain’t Markup Language) file [<xref ref-type="bibr" rid="ref33">33</xref>] or a table within a database [<xref ref-type="bibr" rid="ref43">43</xref>], which were implemented manually. Afterwards, the transformation rules could be used in the ETL/ELT process, for example, to enable the automatic transformation. Other types of MDD approaches can also be implemented by using existing tools (eg, knowledge and metadata repository [<xref ref-type="bibr" rid="ref66">66</xref>]) or use case specific tools (eg, metadata repository [<xref ref-type="bibr" rid="ref41">41</xref>] and metadata management framework [<xref ref-type="bibr" rid="ref60">60</xref>]). For example, Ozyurt and Grethe [<xref ref-type="bibr" rid="ref36">36</xref>] implemented a generic transformation language using the bioCADDIE Data Tag Suite (bioCADDIE Project) [<xref ref-type="bibr" rid="ref67">67</xref>] (a metadata schema) to align heterogeneous data from multiple sources, which provided a basis for further analytic queries.</p>
        <fig id="figure4" position="float">
          <label>Figure 4</label>
          <caption>
            <p>Tools used for developing the metadata-driven approach. MMF: metadata management framework; OWL: Web Ontology Language; YAML: YAML Ain’t Markup Language.</p>
          </caption>
          <graphic xlink:href="medinform_v12i1e52967_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <p>Our literature review on the topic “metadata-driven ETL/ELT” includes all publications listed on PubMed, IEEE Explore, Web of Science, and Biomed Center on MDD ETL/ELT process from 2012 to 2022. In some context, the use of metadata is represented specifically using “ontology” or “rules.” Therefore, we added “ontology” and “rules” into the search string to expand the search range.</p>
        <p>With the review process presented, we were able to provide an overview of the thematic categories to which the MDD ETL/ELT processes were applied (Q1), the types of MDD approaches used in the ETL/ELT processes (Q2), the purposes of using MDD approaches (Q3), as well as the tools used to implement the MDD approaches (Q4).</p>
        <p>Across all thematic categories, ontology-based and rule-based approaches are the most used approaches in the data warehouse and the medical thematic categories. In some cases, more than one MDD approach was used in the ETL/ELT process. For example, Del Carmen Legaz-García et al [<xref ref-type="bibr" rid="ref39">39</xref>] used both ontology-based and rule-based approaches. Therefore, such publications were categorized as both MDD approach types.</p>
        <p>Various tools can be used to implement MDD approaches. Unfortunately, we were not able to extract this information from all included publications. The reason for that is that some publications used proprietary or nontransferable approaches (eg, data-specific ontologies [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref62">62</xref>] and rules from Data Vault [DataVaultAlliance] [<xref ref-type="bibr" rid="ref42">42</xref>]). Some other publications did not explicitly mention or describe the tools they used. Therefore, these publications were not included in the analysis of MDD tools used.</p>
        <p>The results indicate that it is promising to implement a generic ETL/ELT process to transform different FHIR profiles to OMOP CDM automatically by applying MDD approaches. However, the results do not provide a trivial solution for this. For example, Huang et al [<xref ref-type="bibr" rid="ref63">63</xref>] used an ontology-based approach to be able to automate the data transformation in an ETL/ELT process, while Ong et al [<xref ref-type="bibr" rid="ref34">34</xref>] used a rule-based approach to achieve the same purpose. In some cases, more than one MDD approach were used as complements in order to accomplish the data transformation. For example, Pacaci et al [<xref ref-type="bibr" rid="ref37">37</xref>] chose an ontology-based approach to automate the data transformation and a rule-based to simplify the maintenance of the transformation process in case of changes in data sources. By applying these 2 approaches in combination, the authors were able to transform EHR data from heterogeneous EHR systems into OMOP CDM. Therefore, determining an appropriate MDD approach and tool to implement a generic ETL/ELT process to transform FHIR to OMOP CDM automatically remains a challenge.</p>
        <p>This work aimed to provide an overview of different types of MDD approaches and their tools. Consequently, this review lacks an analysis of detailing the specific traits of each MDD approach. This gap underscores the importance of providing a comprehensive insight into the characterizations of the MDD approaches presented in this study. This analysis will be conducted in the future to provide solid evidence for selecting the most suitable MDD approach and tool, or for considering using multiple MDD approaches in combination to implement the generic ETL/ELT process for transforming FHIR to OMOP CDM.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Our literature review shows that using MDD approaches to develop an ETL/ELT process can serve different purposes in different focus groups (ie, medicine, data warehouse, big data, industry, geoinformatics, archaeology, and military). The results show that it is promising to implement an ETL/ELT process by applying MDD approach for automating the data transformation from FHIR to OMOP CDM. However, the determination of an appropriate MDD approach and tool to implement such an ETL/ELT process remains a challenge. This is due to the lack of comprehensive insight into the characterizations of the MDD approaches presented in this study. Therefore, our next step is to evaluate the MDD approaches presented in this study and to determine the most appropriate MDD approaches and the way of integrating them into the MII CDS FHIR to OMOP CDM ETL process [<xref ref-type="bibr" rid="ref8">8</xref>]. This could verify the ability of using MDD approaches to generalize the ETL process for harmonizing medical data [<xref ref-type="bibr" rid="ref11">11</xref>].</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>Excel tables for extracted data from included publications.</p>
        <media xlink:href="medinform_v12i1e52967_app1.xlsx" xlink:title="XLSX File  (Microsoft Excel File), 462 KB"/>
      </supplementary-material>
      <supplementary-material id="app2">
        <label>Multimedia Appendix 2</label>
        <p>PRISMA-ScR checklist.</p>
        <media xlink:href="medinform_v12i1e52967_app2.docx" xlink:title="DOCX File , 85 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">CDM</term>
          <def>
            <p>Common Data Model</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">CDS</term>
          <def>
            <p>Core Data Set</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">DARWIN EU</term>
          <def>
            <p>Data Analysis and Real World Interrogation Network European Union</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">EHR</term>
          <def>
            <p>electronic health record</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">ELT</term>
          <def>
            <p>Extract-Load-Transform</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">ETL</term>
          <def>
            <p>Extract-Transform-Load</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">FHIR</term>
          <def>
            <p>Fast Healthcare Interoperability Resources</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">FTS</term>
          <def>
            <p>full-text screening</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb9">HL7</term>
          <def>
            <p>Health Level 7</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb10">KBV</term>
          <def>
            <p>The National Association of Statutory Health Insurance Physicians (German: Kassenärztliche Bundesvereinigung)</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb11">MDD</term>
          <def>
            <p>metadata-driven</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb12">MII</term>
          <def>
            <p>Medical Informatics Initiative</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb13">OMOP</term>
          <def>
            <p>Observational Medical Outcomes Partnership</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb14">PRISMA</term>
          <def>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb15">TAS</term>
          <def>
            <p>Title-Abstract-Screening</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb16">YAML</term>
          <def>
            <p>YAML Ain’t Markup Language</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>This publication was partially funded by the German Federal Ministry of Education and Research (BMBF) Network of University Medicine 2.0: “NUM 2.0”, Grant No. 01KX2121, Project: NUM-Data integration center – NUM-DIZ. The Article Processing Charge was funded by the joint publication funds of the Technische Universität, Dresden, including the Carl Gustav Carus Faculty of Medicine, and the Sächsische Landesbibliothek—Staats- und Universitätsbibliothek, Dresden, as well as the Open Access Publication Funding of the Deutsche Forschungsgemeinschaft.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>All authors contributed substantially to this work. YP did the search string definition and publications for the review-process preparation. YP, FB, Robert G, AH, EH, DK, SL, and AV: screened the title and abstract. YP, FB, Richard G, Robert G, AH, EH, DK, SL, and AV screened the full text. YP did the data extraction. FB, DK, Robert G, and SL performed the data extraction validation. YP wrote the original draft. YP, FB, Richard G, Robert G, AH, EH, DK, SL, AV, and MS reviewed and edited the writing. MS handled the resources. All authors have read and agreed to the current version of the paper and take responsibility for the scientific integrity of the work.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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