{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:40Z","timestamp":1787014060901,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Translational multidisciplinary research is important for the Center for Devices and Radiological Health's efforts for utilizing real\u2010world data (\n                    <jats:styled-content style=\"fixed-case\">RWD<\/jats:styled-content>\n                    ) to enhance predictive evaluation of medical device performance in patient subpopulations. As part of our efforts for developing new\n                    <jats:styled-content style=\"fixed-case\">RWD<\/jats:styled-content>\n                    \u2010based evidentiary approaches, including\n                    <jats:italic>in silico<\/jats:italic>\n                    discovery of device\u2010related risk predictors and biomarkers, this study aims to characterize the sex\/race\u2010related trends in hip replacement outcomes and identify corresponding candidate single nucleotide polymorphisms (SNPs). Adverse outcomes were assessed by deriving\n                    <jats:styled-content style=\"fixed-case\">RWD<\/jats:styled-content>\n                    from a retrospective analysis of hip replacement hospital discharge data from the National Inpatient Sample (\n                    <jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content>\n                    ). Candidate\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    s were explored using pre\u2010existing data from the Personalized Medicine Research Project (\n                    <jats:styled-content style=\"fixed-case\">PMRP<\/jats:styled-content>\n                    ). High\u2010Performance Integrated Virtual Environment was used for analyzing and visualizing putative associations between\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    s and adverse outcomes. Ingenuity Pathway Analysis (\n                    <jats:styled-content style=\"fixed-case\">IPA<\/jats:styled-content>\n                    ) was used for exploring plausibility of the sex\u2010related candidate\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    s and characterizing gene networks associated with the variants of interest. The\n                    <jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content>\n                    \u2010based epidemiologic evidence showed that periprosthetic osteolysis (\n                    <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>\n                    ) was most prevalent among white men. The\n                    <jats:styled-content style=\"fixed-case\">PMRP<\/jats:styled-content>\n                    \u2010based genetic evidence associated the\n                    <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>\n                    \u2010related male predominance with rs7121 (odds ratio\u00a0=\u00a04.89; 95% confidence interval\u00a0=\u00a01.41\u221217.05) and other candidate\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    s.\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    \u2010based\n                    <jats:styled-content style=\"fixed-case\">IPA<\/jats:styled-content>\n                    analysis of the expected gene expression alterations and corresponding signaling pathways suggested possible role of sex\u2010related metabolic factors in development of\n                    <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>\n                    , which was substantiated by\n                    <jats:italic>ad hoc<\/jats:italic>\n                    epidemiologic analysis identifying the sex\u2010related differences in metabolic comorbidities in men vs. women with hip replacement\u2010related\n                    <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>\n                    . Thus, our\n                    <jats:italic>in silico<\/jats:italic>\n                    study illustrates\n                    <jats:styled-content style=\"fixed-case\">RWD<\/jats:styled-content>\n                    \u2010based evidentiary approaches that may facilitate cost\/time\u2010efficient discovery of biomarkers for informing use of medical products.\n                  <\/jats:p>","DOI":"10.1111\/cts.12685","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T08:58:40Z","timestamp":1565081920000},"page":"98-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of an Integrated Platform Using Multidisciplinary Real\u2010World Data to Facilitate Biomarker Discovery for Medical Products"],"prefix":"10.1111","volume":"13","author":[{"given":"Stefan","family":"Dabic","sequence":"first","affiliation":[{"name":"Center for Devices and Radiological Health US Food and Drug Administration (CDRH\/FDA) Silver Spring Maryland USA"},{"name":"High\u2010Performance Integrated Virtual Environment (HIVE) US Food and Drug Administration (FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasameen","family":"Azarbaijani","sequence":"additional","affiliation":[{"name":"Center for Devices and Radiological Health US Food and Drug Administration (CDRH\/FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9911-5315","authenticated-orcid":false,"given":"Tigran","family":"Karapetyan","sequence":"additional","affiliation":[{"name":"Center for Devices and Radiological Health US Food and Drug Administration (CDRH\/FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilsa","family":"Loyo\u2010Berrios","sequence":"additional","affiliation":[{"name":"Center for Devices and Radiological Health US Food and Drug Administration (CDRH\/FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahan","family":"Simonyan","sequence":"additional","affiliation":[{"name":"High\u2010Performance Integrated Virtual Environment (HIVE) US Food and Drug Administration (FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrie","family":"Kitchner","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Marshfield Clinic Research Institute (MCRI) Marshfield Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Brilliant","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Marshfield Clinic Research Institute (MCRI) Marshfield Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2565-3118","authenticated-orcid":false,"given":"Yelizaveta","family":"Torosyan","sequence":"additional","affiliation":[{"name":"Center for Devices and Radiological Health US Food and Drug Administration (CDRH\/FDA) Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"2016\u20132017 Strategic Priorities Center for Devices and Radiological Health. <https:\/\/www.fda.gov\/downloads\/AboutFDA\/CentersOffices\/OfficeofMedicalProductsandTobacco\/CDRH\/CDRHVisionandMission\/UCM481588.pdf>. 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