{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:37:23Z","timestamp":1791657443859,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000261","name":"Multiple Sclerosis Society of Canada","doi-asserted-by":"publisher","award":["AWD\u2010028466"],"award-info":[{"award-number":["AWD\u2010028466"]}],"id":[{"id":"10.13039\/501100000261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010156363"],"award-info":[{"award-number":["PJT\u2010156363"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN\u2010159934"],"award-info":[{"award-number":["FDN\u2010159934"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Given the historical use of limited confounders in multiple sclerosis (MS) studies utilizing administrative health data, this brief report evaluates the impact of incorporating high\u2010dimensional proxy information on confounder adjustment in MS research. We have implemented high\u2010dimensional propensity score (hdPS) and high\u2010dimensional disease risk score (hdDRS) methods to assess changes in effect estimates for the association between disease\u2010modifying drugs (DMDs) and all\u2010cause mortality in an MS cohort from British Columbia (BC), Canada.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a population\u2010based retrospective study using linked administrative databases from BC, including health insurance registries, demographics, physician visits, hospitalizations, prescriptions, and vital statistics. The cohort comprised 19\u2009360 individuals with MS, followed from January 1, 1996, to December 31, 2017. DMD exposure was defined as at least 180\u2009days of use for beta\u2010interferon or glatiramer acetate, or at least 90\u2009days for other DMDs. The outcome was time to all\u2010cause mortality. We compared Cox proportional hazards models adjusting for investigator\u2010specified covariates with those incorporating additional empirical covariates using hdPS and hdDRS methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the unadjusted analysis, DMD exposure was associated with a 69% lower risk of mortality (HR 0.31; 95% CI: 0.27\u20130.36). Adjusting for investigator\u2010specified covariates, the adjusted hazard ratio (aHR) was 0.76 (95% CI: 0.65\u20130.89). HdPS analyses showed a 20%\u201323% lower mortality risk (aHRs: 0.77 to 0.80), while hdDRS analyses indicated a 19%\u201321% reduction (aHRs: 0.79 to 0.81).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Incorporating high\u2010dimensional proxy information resulted in minor variations in effect estimates compared to traditional covariate adjustment. These findings suggest that the impact of residual confounding in the question under consideration may be modest. Further research should explore additional data dimensions and replicate these findings across different datasets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70112","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:19:16Z","timestamp":1738628356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluating the Role of High\u2010Dimensional Proxy Data in Confounding Adjustment in Multiple Sclerosis Research: A Case Study"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0346-2871","authenticated-orcid":false,"given":"Mohammad Ehsanul","family":"Karim","sequence":"first","affiliation":[{"name":"School of Population and Public Health University of British Columbia  Vancouver British Columbia Canada"},{"name":"Centre for Advancing Health Outcomes, University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-863X","authenticated-orcid":false,"given":"Md. Belal","family":"Hossain","sequence":"additional","affiliation":[{"name":"School of Population and Public Health University of British Columbia  Vancouver British Columbia Canada"},{"name":"Centre for Advancing Health Outcomes, University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huah Shin","family":"Ng","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health Flinders University  Adelaide Australia"},{"name":"SA Pharmacy SA Health  Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine The Djavad Mowafaghian Centre for Brain Health, University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna A.","family":"Frank","sequence":"additional","affiliation":[{"name":"School of Population and Public Health University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-2535","authenticated-orcid":false,"given":"Helen","family":"Tremlett","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine The Djavad Mowafaghian Centre for Brain Health, University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2015.10.006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829a3388"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-300616"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211063403"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200005"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12990"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181a663cc"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/00031305.2024.2368794"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv108"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000787"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx032"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwad196"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181cf6ec0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz055"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319831"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61769-3"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6809-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1230"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5121"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(92)90133-8"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000495"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlr.0000182534.19832.83"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12982-016-0047-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.794075"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv445"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70112","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pds.70112","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:43:50Z","timestamp":1788317030000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.70112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/pds.70112"],"URL":"https:\/\/doi.org\/10.1002\/pds.70112","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70112"}}