Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data</title><author><name sortKey="Kass Hout, Taha A" sort="Kass Hout, Taha A" uniqKey="Kass Hout T" first="Taha A" last="Kass-Hout">Taha A. Kass-Hout</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Xu, Zhiheng" sort="Xu, Zhiheng" uniqKey="Xu Z" first="Zhiheng" last="Xu">Zhiheng Xu</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Mohebbi, Matthew" sort="Mohebbi, Matthew" uniqKey="Mohebbi M" first="Matthew" last="Mohebbi">Matthew Mohebbi</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Nelsen, Hans" sort="Nelsen, Hans" uniqKey="Nelsen H" first="Hans" last="Nelsen">Hans Nelsen</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Baker, Adam" sort="Baker, Adam" uniqKey="Baker A" first="Adam" last="Baker">Adam Baker</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Levine, Jonathan" sort="Levine, Jonathan" uniqKey="Levine J" first="Jonathan" last="Levine">Jonathan Levine</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Johanson, Elaine" sort="Johanson, Elaine" uniqKey="Johanson E" first="Elaine" last="Johanson">Elaine Johanson</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Bright, Roselie A" sort="Bright, Roselie A" uniqKey="Bright R" first="Roselie A" last="Bright">Roselie A. Bright</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26644398</idno><idno type="pmc">4901374</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901374</idno><idno type="RBID">PMC:4901374</idno><idno type="doi">10.1093/jamia/ocv153</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000004</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000004</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data</title><author><name sortKey="Kass Hout, Taha A" sort="Kass Hout, Taha A" uniqKey="Kass Hout T" first="Taha A" last="Kass-Hout">Taha A. Kass-Hout</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Xu, Zhiheng" sort="Xu, Zhiheng" uniqKey="Xu Z" first="Zhiheng" last="Xu">Zhiheng Xu</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Mohebbi, Matthew" sort="Mohebbi, Matthew" uniqKey="Mohebbi M" first="Matthew" last="Mohebbi">Matthew Mohebbi</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Nelsen, Hans" sort="Nelsen, Hans" uniqKey="Nelsen H" first="Hans" last="Nelsen">Hans Nelsen</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Baker, Adam" sort="Baker, Adam" uniqKey="Baker A" first="Adam" last="Baker">Adam Baker</name><affiliation><nlm:aff id="ocv153-AFF2">Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</nlm:aff></affiliation></author><author><name sortKey="Levine, Jonathan" sort="Levine, Jonathan" uniqKey="Levine J" first="Jonathan" last="Levine">Jonathan Levine</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Johanson, Elaine" sort="Johanson, Elaine" uniqKey="Johanson E" first="Elaine" last="Johanson">Elaine Johanson</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Bright, Roselie A" sort="Bright, Roselie A" uniqKey="Bright R" first="Roselie A" last="Bright">Roselie A. Bright</name><affiliation><nlm:aff id="ocv153-AFF1">U.S. Food and Drug Administration, Silver Spring, MD, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of the American Medical Informatics Association : JAMIA</title><idno type="ISSN">1067-5027</idno><idno type="eISSN">1527-974X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Objective</bold> The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs).</p><p><bold>Materials and Methods</bold> Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges.</p><p><bold>Results</bold> Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event.</p><p><bold>Conclusion</bold> With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kass Hout, T" uniqKey="Kass Hout T">T Kass-Hout</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kass Hout, T" uniqKey="Kass Hout T">T Kass-Hout</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kass Hout, T" uniqKey="Kass Hout T">T Kass-Hout</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Ramstein, E" uniqKey="Ramstein E">E. Ramstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, J" uniqKey="Levine J">J. Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, J" uniqKey="Levine J">J. Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, J" uniqKey="Levine J">J. Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, J" uniqKey="Levine J">J. Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, J" uniqKey="Levine J">J. Levine</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Tsong, Y" uniqKey="Tsong Y">Y Tsong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcadams, M" uniqKey="Mcadams M">M McAdams</name></author><author><name sortKey="Staffa, J" uniqKey="Staffa J">J Staffa</name></author><author><name sortKey="Dal Pan, G" uniqKey="Dal Pan G">G Dal Pan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dasgupta, N" uniqKey="Dasgupta N">N Dasgupta</name></author><author><name sortKey="Mandl, Kd" uniqKey="Mandl K">KD Mandl</name></author><author><name sortKey="Brownstein, Js" uniqKey="Brownstein J">JS Brownstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bate, A" uniqKey="Bate A">A Bate</name></author><author><name sortKey="Evans, S" uniqKey="Evans S">S Evans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szarfman, A" uniqKey="Szarfman A">A Szarfman</name></author><author><name sortKey="Tonning, Jm" uniqKey="Tonning J">JM Tonning</name></author><author><name sortKey="Doraiswamy, Pm" uniqKey="Doraiswamy P">PM Doraiswamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Subedi, Fh" uniqKey="Subedi F">FH Subedi</name></author><author><name sortKey="Joshi, Ph" uniqKey="Joshi P">PH Joshi</name></author><author><name sortKey="Jones, Sr" uniqKey="Jones S">SR Jones</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Stone, Nj" uniqKey="Stone N">NJ Stone</name></author><author><name sortKey="Robinson, J" uniqKey="Robinson J">J Robinson</name></author><author><name sortKey="Lichtenstein, Ah" uniqKey="Lichtenstein A">AH Lichtenstein</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cefali, Ea" uniqKey="Cefali E">EA Cefali</name></author><author><name sortKey="Simmons, Pd" uniqKey="Simmons P">PD Simmons</name></author><author><name sortKey="Stanek, Ej" uniqKey="Stanek E">EJ Stanek</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Am Med Inform Assoc</journal-id><journal-id journal-id-type="iso-abbrev">J Am Med Inform Assoc</journal-id><journal-id journal-id-type="publisher-id">jamia</journal-id><journal-id journal-id-type="hwp">jaminfo</journal-id><journal-title-group><journal-title>Journal of the American Medical Informatics Association : JAMIA</journal-title></journal-title-group><issn pub-type="ppub">1067-5027</issn><issn pub-type="epub">1527-974X</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26644398</article-id><article-id pub-id-type="pmc">4901374</article-id><article-id pub-id-type="doi">10.1093/jamia/ocv153</article-id><article-id pub-id-type="publisher-id">ocv153</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research and Applications</subject></subj-group></article-categories><title-group><article-title>OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kass-Hout</surname><given-names>Taha A</given-names></name><xref ref-type="aff" rid="ocv153-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Xu</surname><given-names>Zhiheng</given-names></name><xref ref-type="aff" rid="ocv153-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mohebbi</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="ocv153-AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nelsen</surname><given-names>Hans</given-names></name><xref ref-type="aff" rid="ocv153-AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baker</surname><given-names>Adam</given-names></name><xref ref-type="aff" rid="ocv153-AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Levine</surname><given-names>Jonathan</given-names></name><xref ref-type="aff" rid="ocv153-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johanson</surname><given-names>Elaine</given-names></name><xref ref-type="aff" rid="ocv153-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bright</surname><given-names>Roselie A</given-names></name><xref ref-type="aff" rid="ocv153-AFF1"><sup>1</sup></xref></contrib><aff id="ocv153-AFF1"><sup>1</sup>U.S. Food and Drug Administration, Silver Spring, MD, USA</aff><aff id="ocv153-AFF2"><sup>2</sup>Iodine, Inc. 34 Clyde Street, San Francisco, CA 94107, USA</aff></contrib-group><author-notes><corresp>Correspondence to Zhiheng Xu, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA; <email>zhiheng.xu@fda.hhs.gov</email>; Tel: <phone>301-796-6094</phone>; Fax: <fax>301-847-8123</fax></corresp></author-notes><pub-date pub-type="ppub"><month>5</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>07</day><month>12</month><year>2015</year></pub-date><volume>23</volume><issue>3</issue><fpage>596</fpage><lpage>600</lpage><history><date date-type="received"><day>12</day><month>1</month><year>2015</year></date><date date-type="rev-recd"><day>24</day><month>7</month><year>2015</year></date><date date-type="accepted"><day>5</day><month>9</month><year>2015</year></date></history><permissions><copyright-statement>© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.</copyright-statement><copyright-year>2015</copyright-year><license xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" license-type="creative-commons"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com</license-p></license></permissions><abstract><p><bold>Objective</bold> The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs).</p><p><bold>Materials and Methods</bold> Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges.</p><p><bold>Results</bold> Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event.</p><p><bold>Conclusion</bold> With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products.</p></abstract><kwd-group><kwd>openFDA</kwd><kwd>drug safety</kwd><kwd>adverse event</kwd><kwd>API</kwd><kwd>application programming interface</kwd><kwd>open data</kwd><kwd>open source</kwd></kwd-group><counts><page-count count="5"></page-count></counts></article-meta></front><body><sec><title>BACKGROUND AND SIGNIFICANCE</title><p>In the United States, Food and Drug Administration (FDA)-regulated products account for about 25 cents of every dollar spent by American consumers each year—products that touch the lives of every American every day.<xref rid="ocv153-B1" ref-type="bibr"><sup>1</sup></xref> Americans rely on the FDA to keep their food, medical products, and other FDA-regulated products safe, and where applicable, effective. FDA’s major activities regarding marketed products are to:
<list list-type="bullet"><list-item><p>Require firms that manufacture or distribute FDA-regulated products to register with FDA, list the products, and provide the labeling on those products.</p></list-item><list-item><p>Review reports of adverse events, which may include patient or user harm, use error, and/or a quality problem with the product, to monitor marketed products. FDA accepts all voluntary reports and has issued reporting requirements that vary with the particular type of product.</p></list-item><list-item><p>Inspect firms and/or products, either routinely or as part of an investigation prompted by an adverse event report or other concern.</p></list-item><list-item><p>Monitor product recalls, which most often are manufacturer initiated.</p></list-item></list></p><p>FDA has been making non-confidential portions of these data available on <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov">www.fda.gov</ext-link> in 3 modes:
<list list-type="order"><list-item><p>Web-based search tools that return structured and/or unstructured data. These are excellent for occasional use with simple queries.</p></list-item><list-item><p>The entire database downloadable in comma-separated value (CSV) or standard generalized markup language (SGML) format. This mode is only practical for users with broadband internet access, large storage space, statistical software, and the technical skill to properly process the relational database files and any unstructured fields.</p></list-item><list-item><p>Individual files based on popular Freedom of Information Act (FOIA) requests. These files may not be relevant to the user’s questions. Members of the public may also file custom FOIA requests for specific records.</p></list-item></list></p><p>To address these difficulties FDA launched the openFDA project in March 2013.</p><p>The first priority were databases with a combination of high general consumer interest, low accessibility on <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov">www.fda.gov</ext-link>, and high interest on the part of the FDA organization that stewards the database.</p><p>By making the data available to the public in a new harmonized big data format, FDA encourages scientists, clinicians, informaticists, software developers, and other technically focused individuals in both the private and public sectors to explore the data, develop applications that automatically access the data, and offer their own enhancements to the data or the software. The more recent Presidential Executive Order on Open Data<xref rid="ocv153-B2" ref-type="bibr"><sup>2</sup></xref> and the Department of Health and Human Services Health Data Initiative<xref rid="ocv153-B3" ref-type="bibr"><sup>3</sup></xref> require FDA to make its publicly available data more easily accessible in a structured, computer readable format.</p><p>On June 2, 2014, openFDA was launched in Beta mode at <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov">https://open.fda.gov</ext-link>.<xref rid="ocv153-B4" ref-type="bibr"><sup>4</sup></xref> This project uses cutting edge technologies, and is a pilot for how FDA can develop and deploy novel applications in the public cloud securely and efficiently in the future. In this article, we describe the system and demonstrate how to obtain openFDA data through application programming interface (API) calls. A case study illustrates the use of openFDA in investigating an apparent association between a drug and an adverse event.</p></sec><sec sec-type="methods"><title>METHODS</title><sec><title>Data Sources</title><p>Four main data sources are currently available in openFDA:
<list list-type="bullet"><list-item><p>FAERS (FDA Adverse Event Reporting System) for drugs and selected biological products.<xref rid="ocv153-B5" ref-type="bibr"><sup>5–7</sup></xref></p></list-item><list-item><p>SPL (Structured Product Labeling) for drugs and selected biological products.<xref rid="ocv153-B8" ref-type="bibr"><sup>8</sup></xref><sup>,</sup><xref rid="ocv153-B9" ref-type="bibr"><sup>9</sup></xref></p></list-item><list-item><p>RES (Recall Enterprise System), primarily recall notices, and also market withdrawals and safety alerts, for drugs, selected biological products, devices, and foods.<xref rid="ocv153-B10" ref-type="bibr"><sup>10–12</sup></xref></p></list-item><list-item><p>MAUDE (Manufacturer and User Device Experience), adverse event reports for medical devices.<xref rid="ocv153-B13" ref-type="bibr"><sup>13</sup></xref></p></list-item></list></p><p>Details for each data source can be found at <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/updates/">https://open.fda.gov/updates/</ext-link>. To address issues related to differences in the structure of the three drug databases (adverse event reports, recalls, and labeling), openFDA features harmonization on drug identifiers (generic name, brand name, etc.), to make it easier to both search for and understand the drug products returned by API queries (details can be found at <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/updates/">https://open.fda.gov/updates/</ext-link>). When users query a drug database API, they can search either fields original to the database (never deleted) or the harmonized openFDA fields.</p></sec><sec><title>Logical Architecture</title><p>The architecture and technology were chosen to make openFDA scalable; quickly responsive; transferable to new technologies as they mature; easily accessible by application developers, researchers, and the general public; and transparent. The data are on the cloud that has been approved for federal use (Amazon Web Services East).<xref rid="ocv153-B14" ref-type="bibr"><sup>14</sup></xref> Details can be found at <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/updates/">https://open.fda.gov/updates/</ext-link>.</p></sec><sec><title>Design of open.fda.gov</title><p>The design of the open.fda.gov website draws on best practices in agile development, intuitive user experience, and data visualization, aiming to provide one unified, simple presentation to users. The site is organized around broad types of data, rather than FDA’s internal structure. The site is characterized by a combination of interactive programmer-friendly queries, visualizations and examples that help explain the nature of the data and how to use JSON URL query command syntax. Plain language is used throughout.</p></sec><sec><title>Design for Engaged, Open Community</title><p>Users are encouraged to use GitHub<xref rid="ocv153-B15" ref-type="bibr"><sup>15</sup></xref> to see all the open source code and post their own additions or modifications. StackExchange<xref rid="ocv153-B16" ref-type="bibr"><sup>16</sup></xref> is encouraged for discussion, questions, and answers. In addition, FDA publishes update announcements on open.FDA.gov and an openFDA Twitter account, and maintains an openFDA email account is to widen the options for user participation.</p></sec></sec><sec sec-type="results"><title>RESULTS</title><sec><title>Use of openFDA in Applications</title><p>Since the launch of openFDA, a growing community on StackExchange has been engaged in discovering novel ways to use, integrate, and analyze the openFDA data.<xref rid="ocv153-B17" ref-type="bibr"><sup>17</sup></xref> By mid-July 2015, there have been more than 20 million API calls (more than half of which were generated outside the United States), more than 6000 registered API users, and more than 1800 Twitter followers. Twitter has been used to broadcast openFDA news and followers’ feedback and announcements. For example, some followers have shared their experiences of using openFDA to study gender differences in reported drug side effects<xref rid="ocv153-B18" ref-type="bibr"><sup>18</sup></xref> and to cross reference openFDA data with other databases.<xref rid="ocv153-B19" ref-type="bibr"><sup>19</sup></xref></p><p>As a result of the US General Services Administration’s Request for Quotes<xref rid="ocv153-B20" ref-type="bibr"><sup>20</sup></xref> on June 17th<xref rid="ocv153-B21" ref-type="bibr"><sup>21</sup></xref> that requires responders to build working prototype apps that use openFDA and post them in GitHub,<xref rid="ocv153-B22" ref-type="bibr"><sup>22</sup></xref> GitLab,<xref rid="ocv153-B23" ref-type="bibr"><sup>23</sup></xref> or BitBucket,<xref rid="ocv153-B24" ref-type="bibr"><sup>24</sup></xref> dozens of prototypes have been posted on GitHub.</p><p>Apps have been developed that allow a consumer who experiences an adverse event to determine whether there is a report of anyone else having a similar experience after taking the same drug.<xref rid="ocv153-B25" ref-type="bibr"><sup>25–27</sup></xref> An interactive dashboard display of drug reports was published as a “hobby.”<xref rid="ocv153-B28" ref-type="bibr"><sup>28</sup></xref> More advanced statistics are available on a family of public sites<xref rid="ocv153-B29" ref-type="bibr"><sup>29–33</sup></xref> used in the following case study.</p></sec><sec sec-type="cases"><title>Case Study: The Causal Relationship between Aspirin and Flushing</title><p>This case illustrates some of the professional pharmacovigilance processes for assessing an apparent association between a drug and a particular adverse event in a collection of drug adverse event reports summarized in a public FDA guidance document.<xref rid="ocv153-B34" ref-type="bibr"><sup>34</sup></xref> In the past, triggers of increased adverse event reporting to FDA have included news reports, public FDA alerts, and the introduction of new products.<xref rid="ocv153-B35" ref-type="bibr"><sup>35–38</sup></xref> Among the many other issues with drawing causality conclusions from the reports are limited knowledge of the relative extent of use of the drugs involved, and various other alternative explanations for the apparent association. Aspirin is one of the most common drugs listed in openFDA drug adverse event reports (4.2% of all reports). A natural question is what types of adverse events have been reported for aspirin? Or, this could be rephrased as, what types of adverse events were more often reported in the same reports as aspirin, compared to reports that do not mention aspirin? A proportional reporting rate (PRR), a commonly used statistic for this question, of 2 indicates that the proportion of reports for the drug-event combination is twice the proportion of the event in the overall database.<xref rid="ocv153-B34" ref-type="bibr"><sup>34</sup></xref><sup>,</sup><xref rid="ocv153-B38" ref-type="bibr"><sup>38</sup></xref><sup>,</sup><xref rid="ocv153-B39" ref-type="bibr"><sup>39</sup></xref> Using an interactive program designed to look at openFDA drug reports data,<xref rid="ocv153-B29" ref-type="bibr"><sup>29</sup></xref> we can quickly look at the most common events for aspirin (<xref ref-type="table" rid="ocv153-T1">Table 1</xref>). Further details of the steps used in this case can be found at <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/updates/">https://open.fda.gov/updates/</ext-link>.
<table-wrap id="ocv153-T1" orientation="portrait" position="float"><label>Table 1:</label><caption><p>Events reported for generic drug name “aspirin” with PRR > 2.0, ranked by PRR.</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Event rank</th><th rowspan="1" colspan="1">Event</th><th rowspan="1" colspan="1">No. of reports for both aspirin and event</th><th rowspan="1" colspan="1">No. of reports for event</th><th rowspan="1" colspan="1">PRR</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">(any)</td><td rowspan="1" colspan="1">169,838</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">Flushing</td><td rowspan="1" colspan="1">10,071</td><td rowspan="1" colspan="1">42,843</td><td rowspan="1" colspan="1">7.6</td></tr></tbody></table><table-wrap-foot><fn id="ocv153-TF1"><p>Notes: The query URL for all aspirin reports was <ext-link ext-link-type="uri" xlink:href="http://go.usa.gov/cvRTJ">http://go.usa.gov/cvRTJ</ext-link>.Finished data and PRR output was from <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>.<xref rid="ocv153-B29" ref-type="bibr"><sup>29</sup></xref></p></fn><fn id="ocv153-TF3"><p>PRR is the Proportional Reporting Ratio.</p></fn></table-wrap-foot></table-wrap></p><p>“Flushing” is the most common event, with 6% (10 071/169 838) of all reports mentioning aspirin also mentioning flushing. Furthermore, the PRR indicates that a report containing aspirin is more than seven times as likely to include flushing as a report that does not contain aspirin. Labeling for aspirin does not include flushing in the list of adverse events. Before concluding that aspirin causes flushing, one must rule out noncausal explanations of the association, including, but not limited to: 1) the association was a chance occurrence, 2) an extraneous event resulted in the apparent association, 3) the event was related to the underlying condition that prompted the medication use, and 4) other medications are responsible for the relationship.</p><p>Explanations 1) and 2) can be investigated using a dynamic PRR graph (<xref ref-type="fig" rid="ocv153-F1">Figure 1</xref>).
<fig id="ocv153-F1" orientation="portrait" position="float"><label>Figure 1.</label><caption><p>Dynamic proportional reporting ratios (PRR) for reports with aspirin and flushing. At each month, the accumulated reports were used to calculate the PRR and its 95% confidence interval.<xref rid="ocv153-B26" ref-type="bibr"><sup>26</sup></xref></p></caption><graphic xlink:href="ocv153f1p"></graphic></fig></p><p>In <xref ref-type="fig" rid="ocv153-F1">Figure 1</xref> we see that before 2009 there was little or no statistical association between aspirin and flushing, with the PRR values only slightly above 1, and the 95% confidence intervals often including 1. After 2008 we see the PRR rapidly increase to 4, and then increase further to between 7 and 9. The confidence intervals for post 2008 data all exclude 1, so these are unlikely to be a chance association. The dramatic increase after 2008 suggests an explanatory event in 2008.</p><p>In addition, other medication(s) could explain the relationship. Each report allows mentions of multiple drugs and multiple events. <xref ref-type="table" rid="ocv153-T2">Table 2</xref> shows the most common drugs mentioned in reports that also mention aspirin and flushing.
<table-wrap id="ocv153-T2" orientation="portrait" position="float"><label>Table 2.</label><caption><p>Drugs most frequently mentioned in reports with “flushing” events, restricted to those with PRR >2.0.</p></caption><table frame="hsides" rules="groups"><thead align="left"><tr><th rowspan="1" colspan="1">Drug rank</th><th rowspan="1" colspan="1">Drug</th><th rowspan="1" colspan="1">No. of reports for both flushing and drug</th><th rowspan="1" colspan="1">No. of reports for drug</th><th rowspan="1" colspan="1">PRR</th><th rowspan="1" colspan="1">Drug labeling lists flushing in the field “information_for_patients”</th></tr></thead><tbody align="left"><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">(any drug)</td><td rowspan="1" colspan="1">42,841</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">Niacin</td><td rowspan="1" colspan="1">15,303</td><td rowspan="1" colspan="1">36,434</td><td rowspan="1" colspan="1">66</td><td rowspan="1" colspan="1">Yes</td></tr><tr><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">Niacin and
simvastatin</td><td rowspan="1" colspan="1">4975</td><td rowspan="1" colspan="1">10,446</td><td rowspan="1" colspan="1">55</td><td rowspan="1" colspan="1">Yes</td></tr><tr><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">Dimethyl
fumarate</td><td rowspan="1" colspan="1">6234</td><td rowspan="1" colspan="1">24,771</td><td rowspan="1" colspan="1">30</td><td rowspan="1" colspan="1">Yes</td></tr><tr><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">Aspirin</td><td rowspan="1" colspan="1">10,071</td><td rowspan="1" colspan="1">169,838</td><td rowspan="1" colspan="1">7.6</td><td rowspan="1" colspan="1">No</td></tr><tr><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">Lisinopril</td><td rowspan="1" colspan="1">2822</td><td rowspan="1" colspan="1">90,470</td><td rowspan="1" colspan="1">3.3</td><td rowspan="1" colspan="1">Yes</td></tr></tbody></table></table-wrap></p><p>Using openFDA drug labeling, we found that the drugs in <xref ref-type="table" rid="ocv153-T2">Table 2</xref> that list “flushing” are “niacin,” “niacin and simvastatin,” and “lisinopril.” The combination of niacin with simvastatin was first approved as Simcor, February 19, 2008, just before the rise in reports noted in <xref ref-type="fig" rid="ocv153-F1">Figure 1</xref>. Niacin was reported to reduce the risk of myocardial infarction and stroke in 1975, and to reduce atherosclerosis beginning in 1987.<xref rid="ocv153-B40" ref-type="bibr"><sup>40</sup></xref> Consensus guidelines for niacin therapy were published in 2012 and 2013.<xref rid="ocv153-B41" ref-type="bibr"><sup>41</sup></xref><sup>,</sup><xref rid="ocv153-B42" ref-type="bibr"><sup>42</sup></xref> Lisinopril was approved in 1988.<xref rid="ocv153-B43" ref-type="bibr"><sup>43</sup></xref> We then tested whether these three drugs explain all of the apparent association between aspirin and flushing. Looking at aspirin reports that do not mention niacin or lisinopril results in the complete absence of flushing from the list of associated adverse events.</p><p>In summary, we have demonstrated that a drug-event association is unlikely to be causal. Research beyond the reporting data is usually essential to fully understand the relationship between drug-event pairs. For example, Cefali et al.<xref rid="ocv153-B44" ref-type="bibr"><sup>44</sup></xref> found that aspirin is a good way to treat flushing. Our case may be a drug (niacin) causing the event (flushing), and an event (flushing) leading to use of the drug (aspirin).</p></sec></sec><sec sec-type="discussion"><title>DISCUSSION</title><p>The openFDA initiative makes it possible for technology specialists to effectively, automatically, and quickly search, query, or pull massive amounts of public information directly from FDA datasets via URL queries to APIs. As the case study illustrated, openFDA allows users to quickly conduct a variety of analyses to explore the nature of posted data.</p><p>As we focus on making existing public datasets accessible in new ways, it is important to note that only data that has already been cleared for public use is considered for openFDA. This is the practical reason that narrative descriptions of drug adverse event reports are not in the public datasets. The absence of the narratives from the drug reports is enough to prevent drawing any valid conclusions from solely the openFDA drug report data.</p><p>For the first time, the recalls data are more readily searchable and the drug labeling data are searchable on any of the standard labeling fields.</p></sec><sec sec-type="conclusions"><title>CONCLUSION</title><p>OpenFDA brings a new model of big data search and analytics across disparate and complex sources by simplifying dataset structures. With easier and better access, users can learn more about FDA-regulated products, as shown in the case study of aspirin and flushing. A new open community shares code, documentation, examples, apps, and ideas related to openFDA. As the president’s executive order stated, “openness in government…promotes the delivery of efficient and effective services to the public.”<xref rid="ocv153-B2" ref-type="bibr"><sup>2</sup></xref> We invite use of openFDA for entrepreneurship, innovation, and scientific discovery.</p></sec><sec><title>FUNDING</title><p>This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.</p></sec><sec><title>COMPETING INTERESTS</title><p>The authors have no competing interests to declare.</p></sec></body><back><ack><p>The authors wish to acknowledge the ongoing support of the core openFDA team of FDA employees (Steven Hubbard and Kelemework Yimam) and the wider past and current openFDA team (Sharon Campbell, Sean Herron, and Joe Neubauer). The openFDA team has relied heavily on participation by data owners in the FDA programs (Sandra Abbott, Steven Anderson, Yulia Borodina, Erin Brandt, Eric Brodsky, Margarita Brown, Isaac Chang, Lisa Creason, Suranjan De, Ann Ferriter, David Gartner, Marni Hall, David Heller, Randy Levin, Canida Lyle, Elias Mallis, Stanley Milstein, Jonathan Montgomery, Franklin Ohaegbu, Glenn Peterson, John Quinn, Greg Parkover, Lilliam Rosario, Nancy Sager, Jeff Shuren, Ella Smith, Lonnie Smith, Daniel St Laurent, Kevin Starry, Katherine Vierk, and Linda Walter-Grimm); they provided crucial help to prioritize which datasets to make available, get the right data, ensure data quality, and properly document the data. The authors also appreciate support from Ricky Cokely, Mildred Cooper, Andrea Fischer, Janet Gentry, Amber Griffin, Margaret Hamburg, Janet Woodcock, Walter Harris, Joshua Lehman, Angelique Hebert, Milan Kubic, Alan McClelland, Rosie Owens, Jeff Ventura, Bradford Wintermute, Sean Wybenga, and Carolyn Yancey.</p></ack><sec><title>CONTRIBUTORS</title><p>Dr T.A.K.-H. spearheaded the conception and design of the openFDA project. He made significant contributions to the conceptualization of the article and review and synthesis of the literature. Dr Z.X. wrote the initial draft of the manuscript and conducted data analysis. M.M., H.N., A.B., and Russell Power developed openFDA API. Dr J.L. and E.J. conducted case study analysis. Dr R.A.B. contributed content, critical review, and revision of the manuscript.</p></sec><ref-list><title>REFERENCES</title><ref id="ocv153-B1"><label>1</label><mixed-citation publication-type="other">Executive Summary: Strategic Plan for Regulatory Science. <italic>Food and Drug Administration (FDA)</italic>. Updated: January 16, 2013. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm268095.htm">http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm268095.htm</ext-link>. Accessed December 10, 2014.</mixed-citation></ref><ref id="ocv153-B2"><label>2</label><mixed-citation publication-type="other">Executive Order – Making Open and Machine Readable the New Default for Government Information. <italic>Office of the Press Secretary, The White House</italic>. May 9, 2013. <ext-link ext-link-type="uri" xlink:href="http://www.whitehouse.gov/the-press-office/2013/05/09/executive-order-making-open-and-machine-readable-new-default-government-">http://www.whitehouse.gov/the-press-office/2013/05/09/executive-order-making-open-and-machine-readable-new-default-government-</ext-link>. Accessed May 7, 2014.</mixed-citation></ref><ref id="ocv153-B3"><label>3</label><mixed-citation publication-type="other">HHS Open Government Plan. <italic>US Department of Health and Human Services</italic>. Last reviewed January 2, 2015. <ext-link ext-link-type="uri" xlink:href="http://www.hhs.gov/open/plan/opengovernmentplan/initiatives/initiative.html">http://www.hhs.gov/open/plan/opengovernmentplan/initiatives/initiative.html</ext-link>. Accessed March 1, 2014.</mixed-citation></ref><ref id="ocv153-B4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kass-Hout</surname><given-names>T</given-names></name></person-group><article-title>OpenFDA: Innovative Initiative Opens Door to Wealth of FDA’s Publicly Available Data</article-title>. <source>Food and Drug Administration</source>. <comment>June 2, 2014. FDA. <ext-link ext-link-type="uri" xlink:href="http://blogs.fda.gov/fdavoice/index.php/2014/06/openfda-innovative-initiative-opens-door-to-wealth-of-fdas-publicly-available-data">http://blogs.fda.gov/fdavoice/index.php/2014/06/openfda-innovative-initiative-opens-door-to-wealth-of-fdas-publicly-available-data</ext-link>. Accessed March 5, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B5"><label>5</label><mixed-citation publication-type="other">Reports Received and Reports Entered into FAERS by Year. <italic>Food and Drug Administration</italic>. August 6, 2014. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm070434.htm">http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm070434.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B6"><label>6</label><mixed-citation publication-type="other">The Adverse Event Reporting System (AERS): Older Quarterly Data Files. <italic>Food and Drug Administration</italic>. August 15, 2013. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm083765.htm">http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm083765.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B7"><label>7</label><mixed-citation publication-type="other">FDA Adverse Event Reporting System (FAERS): Latest Quarterly Data Files. <italic>Food and Drug Administration</italic>. June 16, 2015. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082193.htm">http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082193.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kass-Hout</surname><given-names>T</given-names></name></person-group><article-title>Providing easy public access to prescription drug, over-the-counter drug, and biological product labeling</article-title>. <source>Food and Drug Administration</source>. <comment>August 18, 2014. <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/update/drug-product-labeling/">https://open.fda.gov/update/drug-product-labeling/</ext-link>. Accessed December 10, 2014</comment>.</mixed-citation></ref><ref id="ocv153-B9"><label>9</label><mixed-citation publication-type="other">DailyMed. <italic>National Library of Medicine, US National Institutes of Health</italic>. <ext-link ext-link-type="uri" xlink:href="http://dailymed.nlm.nih.gov/dailymed/">http://dailymed.nlm.nih.gov/dailymed/</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B10"><label>10</label><mixed-citation publication-type="other">Enforcement Reports. <italic>Food and Drug Administration</italic>. July 15, 2015. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/Safety/Recalls/EnforcementReports/default.htm">http://www.fda.gov/Safety/Recalls/EnforcementReports/default.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B11"><label>11</label><mixed-citation publication-type="other">FDA 101: Product Recalls – From First Alert to Effectiveness Checks. <italic>Food and Drug Administration</italic>. Updated April 29, 2015. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049070.htm">http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049070.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kass-Hout</surname><given-names>T</given-names></name></person-group><article-title>OpenFDA provides ready access to recall data</article-title>. <source>Food and Drug Administration</source>. <comment>August 8, 2014. <ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/update/openfda-provides-ready-access-to-recall-data">https://open.fda.gov/update/openfda-provides-ready-access-to-recall-data</ext-link>. Accessed July 2015</comment>.</mixed-citation></ref><ref id="ocv153-B13"><label>13</label><mixed-citation publication-type="other">Manufacturer and User Facility Device Experience Database – (MAUDE). <italic>Food and Drug Administration</italic>. May 7, 2015. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/ReportingAdverseEvents/ucm127891.htm">http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/ReportingAdverseEvents/ucm127891.htm</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B14"><label>14</label><mixed-citation publication-type="other">FedRAMP Compliant Systems. <italic>FedRAMP, US General Services Administration</italic>. <ext-link ext-link-type="uri" xlink:href="https://www.fedramp.gov/marketplace/compliant-systems/">https://www.fedramp.gov/marketplace/compliant-systems/</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B15"><label>15</label><mixed-citation publication-type="other">FDA/openFDA. <italic>GitHub, Inc</italic>. 2015. <ext-link ext-link-type="uri" xlink:href="https://github.com/FDA/openfda">https://github.com/FDA/openfda</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B16"><label>16</label><mixed-citation publication-type="other">StackExchange. <italic>StackExchange</italic>. <ext-link ext-link-type="uri" xlink:href="http://stackexchange.com/search?q=openFDA">http://stackexchange.com/search?q=openFDA</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B17"><label>17</label><mixed-citation publication-type="other">OpenFDA. <italic>Stack Exchange</italic>. <ext-link ext-link-type="uri" xlink:href="https://opendata.stackexchange.com/search?q=openFDA">https://opendata.stackexchange.com/search?q=openFDA</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B18"><label>18</label><mixed-citation publication-type="other">James G. (@gupta_james). “see how men & women get different drug side effects genderedreactions.com – a @GenderMedKI and @TheThinkTrain project using @openFDA data.” September 1, 2014, 2:23pm. Tweet.</mixed-citation></ref><ref id="ocv153-B19"><label>19</label><mixed-citation publication-type="other">Glenn V. (@TusculumGolfer). “do any of your drug databases have both the @US_FDA @FDA_Drug_Info NDC and @WHO ATC codes listed for each drug? To cross reference.” December 10, 2014, 7:07pm. Tweet.</mixed-citation></ref><ref id="ocv153-B20"><label>20</label><mixed-citation publication-type="other">Request for Quotation (RFQ) 4QTFHS150004 for the Establishment of Multiple Award Blanket Purchase Agreements (BPAs for Agile Delivery Services (ADS I). <italic>US General Services Administration</italic>. <ext-link ext-link-type="uri" xlink:href="https://pages.18f.gov/ads-bpa/assets/ADS_RFQ_Final.pdf">https://pages.18f.gov/ads-bpa/assets/ADS_RFQ_Final.pdf</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B21"><label>21</label><mixed-citation publication-type="other">The Agile Delivery BPA is (almost) here! <italic>US General Services Administration</italic>. June 15, 2015. <ext-link ext-link-type="uri" xlink:href="https://18f.gsa.gov/2015/06/15/agile-bpa-is-here/">https://18f.gsa.gov/2015/06/15/agile-bpa-is-here/</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B22"><label>22</label><mixed-citation publication-type="other">GitHub. <italic>GitHub, Inc</italic>. <ext-link ext-link-type="uri" xlink:href="https://github.com">https://github.com</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B23"><label>23</label><mixed-citation publication-type="other">Create, review and deploy code together<italic>. GitLab</italic>. <ext-link ext-link-type="uri" xlink:href="https://about.gitlab.com/">https://about.gitlab.com/</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B24"><label>24</label><mixed-citation publication-type="other">Your team, your code, connected. <italic>Atlassian, Inc</italic>. <ext-link ext-link-type="uri" xlink:href="https://bitbucket.org">https://bitbucket.org</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B25"><label>25</label><mixed-citation publication-type="other">Track, report, or subscribe to side effects of drugs, vaccines and medical devices. <italic>RecallGuide</italic>. <ext-link ext-link-type="uri" xlink:href="https://www.recallguide.org">https://www.recallguide.org</ext-link>. Accessed July 18, 2015.</mixed-citation></ref><ref id="ocv153-B26"><label>26</label><mixed-citation publication-type="other">Drug Side Effects. <italic>PatientsVille</italic>. 2015. <ext-link ext-link-type="uri" xlink:href="http://www.Patientsville.com">http://www.Patientsville.com</ext-link>. Accessed February 20, 2015.</mixed-citation></ref><ref id="ocv153-B27"><label>27</label><mixed-citation publication-type="other">Welcome to ResearchAE.com. <italic>Social Health Insights LLC</italic>. 2014. <ext-link ext-link-type="uri" xlink:href="http://www.researchae.com">http://www.researchae.com</ext-link>. Accessed December 10, 2014.</mixed-citation></ref><ref id="ocv153-B28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ramstein</surname><given-names>E.</given-names></name></person-group><article-title>openFDA drug adverse events dataviz</article-title>. <source>YouTube</source>. <comment>June 8, 2014. <ext-link ext-link-type="uri" xlink:href="https://www.youtube.com/watch?v=qtSfJUSbMmI&feature=youtu.be">https://www.youtube.com/watch?v=qtSfJUSbMmI&feature=youtu.be</ext-link>. Accessed May 15, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B29"><label>29</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Levine</surname><given-names>J.</given-names></name></person-group><article-title>openFDA RR</article-title>. <comment><ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>. Accessed July 18, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B30"><label>30</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Levine</surname><given-names>J.</given-names></name></person-group><article-title>openFDA RR-Event</article-title>. <comment><ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>. Accessed July 18, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B31"><label>31</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Levine</surname><given-names>J.</given-names></name></person-group><article-title>openFDA Dynamic PRR</article-title>. <comment><ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>. Accessed July 18, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B32"><label>32</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Levine</surname><given-names>J.</given-names></name></person-group><article-title>openFDA Change Point Analysis</article-title>. <comment><ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>. Accessed July 18, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B33"><label>33</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Levine</surname><given-names>J.</given-names></name></person-group><article-title>Report Browser</article-title>. <comment><ext-link ext-link-type="uri" xlink:href="https://open.fda.gov/static/docs/openFDA-analysis-example.pdf">https://open.fda.gov/static/docs/openFDA-analysis-example.pdf</ext-link>. Accessed July 18, 2015</comment>.</mixed-citation></ref><ref id="ocv153-B34"><label>34</label><mixed-citation publication-type="other">Guidance for Industry. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. <italic>Food and Drug Administration, US Department of Health and Human Services</italic>. March, 2005. <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126834.pdf">http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126834.pdf</ext-link>. Accessed February 20, 2015.</mixed-citation></ref><ref id="ocv153-B35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tsong</surname><given-names>Y</given-names></name></person-group><article-title>Comparing reporting rates of adverse events between drugs with adjustment for year of marketing and secular trends in total reporting</article-title>. <source>J Biopharm Stat.</source><year>1995</year>;<volume>5</volume>:<fpage>95</fpage>–<lpage>114</lpage>.<pub-id pub-id-type="pmid">7613562</pub-id></mixed-citation></ref><ref id="ocv153-B36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McAdams</surname><given-names>M</given-names></name><name><surname>Staffa</surname><given-names>J</given-names></name><name><surname>Dal Pan</surname><given-names>G</given-names></name></person-group><article-title>Estimating the extent of reporting to FDA: a case study of statin-associated rhabdomyolysis</article-title>. <source><italic>Pharmacoepidemiol Drug Safety</italic>.</source><year>2008</year>;<volume>17</volume>(<issue>3</issue>):<fpage>229</fpage>–<lpage>239</lpage>.</mixed-citation></ref><ref id="ocv153-B37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dasgupta</surname><given-names>N</given-names></name><name><surname>Mandl</surname><given-names>KD</given-names></name><name><surname>Brownstein</surname><given-names>JS</given-names></name></person-group><article-title>Breaking the news or fueling the epidemic? Temporal association between news media report volume and opioid-related mortality</article-title>. <source><italic>PLoS One</italic>.</source><year>2009</year>;<volume>4</volume>(<issue>11</issue>):<fpage>e7758</fpage>.<pub-id pub-id-type="pmid">19924221</pub-id></mixed-citation></ref><ref id="ocv153-B38"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bate</surname><given-names>A</given-names></name><name><surname>Evans</surname><given-names>S</given-names></name></person-group><article-title>Quantitative signal detection using spontaneous ADR reporting</article-title>. <source>Pharmacoepidemiol Drug Saf</source><year>2009</year>;<volume>18</volume>(<issue>6</issue>):<fpage>427</fpage>–<lpage>436</lpage>.<pub-id pub-id-type="pmid">19358225</pub-id></mixed-citation></ref><ref id="ocv153-B39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Szarfman</surname><given-names>A</given-names></name><name><surname>Tonning</surname><given-names>JM</given-names></name><name><surname>Doraiswamy</surname><given-names>PM</given-names></name></person-group><article-title>Pharmacovigilance in the 21st century: new systematic tools for an old problem</article-title><italic>. </italic><source>Pharmacotherapy</source><year>2004</year>;<volume>24</volume>(<issue>9</issue>):<fpage>1099</fpage>–<lpage>1104</lpage>.<pub-id pub-id-type="pmid">15460169</pub-id></mixed-citation></ref><ref id="ocv153-B40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Subedi</surname><given-names>FH</given-names></name><name><surname>Joshi</surname><given-names>PH</given-names></name><name><surname>Jones</surname><given-names>SR</given-names></name><etal></etal></person-group><article-title>Current guidelines for high-density lipoprotein cholesterol in therapy and future directions</article-title>. <source>Vasc Health Risk Manag</source>. <year>2014</year>;<volume>10</volume>:<fpage>205</fpage>–<lpage>216</lpage>.<pub-id pub-id-type="pmid">24748800</pub-id></mixed-citation></ref><ref id="ocv153-B41"><label>41</label><mixed-citation publication-type="other">Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. <italic>National Guideline Clearinghouse, Agency for Healthcare Research and Quality</italic>. 2012. <ext-link ext-link-type="uri" xlink:href="http://www.guideline.gov/content.aspx?id=38432&search=niacin">www.guideline.gov/content.aspx?id=38432&search=niacin</ext-link>. Accessed May 15, 2015.</mixed-citation></ref><ref id="ocv153-B42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stone</surname><given-names>NJ</given-names></name><name><surname>Robinson</surname><given-names>J</given-names></name><name><surname>Lichtenstein</surname><given-names>AH</given-names></name><etal></etal></person-group><article-title>ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults</article-title>. <source>Circulation</source>. <year>2013</year>;<volume>129</volume>(<issue>25 Suppl 2</issue>):<fpage>S1</fpage>–<lpage>S45</lpage>. <comment>DOI: 10.1161/01.cir.0000437738.63853.7a.</comment><pub-id pub-id-type="pmid">24222016</pub-id></mixed-citation></ref><ref id="ocv153-B43"><label>43</label><mixed-citation publication-type="other">Drugs@FDA: FDA Approved Drug Products. Searched for “Zestril”. <italic>Food and Drug Administration</italic>. <ext-link ext-link-type="uri" xlink:href="http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm">http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm</ext-link>. Accessed May 15, 2015.</mixed-citation></ref><ref id="ocv153-B44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cefali</surname><given-names>EA</given-names></name><name><surname>Simmons</surname><given-names>PD</given-names></name><name><surname>Stanek</surname><given-names>EJ</given-names></name><etal></etal></person-group><article-title>Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation</article-title><italic>. </italic><source>Int J Clin Pharmacol Ther.</source><year>2007</year>;<volume>45</volume>(<issue>2</issue>):<fpage>78</fpage>–<lpage>88</lpage>.<pub-id pub-id-type="pmid">17323787</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Informatique/explor/SgmlV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000004 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000004 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Informatique
|area= SgmlV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |