{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:06:09Z","timestamp":1779192369065,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"8-9","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The self\u2010controlled case series (SCCS) method is frequently employed to explore the relationship between transient exposures and subsequent health events, utilizing data from individuals who have experienced the event of interest. Conventional spline\u2010based SCCS models typically do not account for overlapping exposure periods and fail to accommodate complex interactive effects among multiple exposures. In this paper, we introduce a novel semiparametric SCCS method that employs a functional partial\u2010linear single index (PLSI) link function, allowing for the estimation of overlapping exposure risks. Our approach offers greater interpretability and flexibility compared with existing methods by consolidating multiple exposures into a single index and modeling complex interactions through a nonparametric link function. We validate our model through simulation studies comparing its performance with standard methods under various practical exposure settings. Furthermore, we apply our method to two real\u2010world datasets involving MMR vaccination and malaria chemoprevention, demonstrating its practical utility and enhanced capability to handle multiple, overlapping exposures effectively. Our findings suggest that the PLSI\u2010SCCS model is a robust tool for modern epidemiological and pharmaceutical research, providing a nuanced understanding of exposure effects, particularly in complex multi\u2010exposure scenarios.<\/jats:p>","DOI":"10.1002\/sim.70552","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:11:17Z","timestamp":1776172277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Flexible and Interpretable Modeling of Overlapping Exposure Risks in Self\u2010Controlled Case Series Analysis"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-8832","authenticated-orcid":false,"given":"Xuezhixing","family":"Zhang","sequence":"first","affiliation":[{"name":"Centre for Biomedical Data Science, Duke\u2010NUS Medical School National University of Singapore  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-3395","authenticated-orcid":false,"given":"Paul","family":"Milligan","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-7625","authenticated-orcid":false,"given":"Yin Bun","family":"Cheung","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Data Science, Duke\u2010NUS Medical School National University of Singapore  Singapore"},{"name":"Tampere Center for Child, Adolescent and Maternal Health Research Tampere University  Tampere Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533328"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2302"},{"key":"e_1_2_9_4_1","volume-title":"Use of the Self\u2010Controlled Case Series Method Beyond Vaccine Safety: A Review and Discussion","author":"Ghebremichael\u2010Weldeselassie Y.","year":"2018"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-022-01520-w"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-024-03687-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-024-00969-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003523"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2022.10.019"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280208092342"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00097-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5949"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.201400257"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7311"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.10049"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.78.4.742"},{"issue":"3","key":"e_1_2_9_17_1","first-page":"1","article-title":"Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)","volume":"59","author":"Marin M.","year":"2010","journal-title":"MMWR Recommendations and Reports"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-026953"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8040676"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwaf115"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176347963"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1214\/09-AOS712"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/sjos.12178"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-019-0557-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429491313"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1997.10474001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1198\/016214502388618861"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1038425655"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1198\/106186002853"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2307\/2534006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.06.010"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","unstructured":"S.MaandX.He \u201cInference for Single\u2010Index Quantile Regression Models With Profile Optimization \u201d(2016).","DOI":"10.1214\/15-AOS1404"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13702"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/imamat\/6.1.76"},{"key":"e_1_2_9_35_1","volume-title":"Introduction to Numerical Analysis","author":"Hildebrand F. B.","year":"1987"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90471-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.3.351"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7519.727"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7319"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2021.1998099"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3601-3606.2005"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01075-10"},{"issue":"5","key":"e_1_2_9_43_1","first-page":"10","article-title":"Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: A Pooled Analysis to Inform Optimal Dosing in African Children With Uncomplicated Malaria","volume":"62","author":"Kock M.","year":"2018","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2015.04.007"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-020-01194-6"},{"issue":"2","key":"e_1_2_9_46_1","first-page":"1","article-title":"General Recommendations on Immunization","volume":"60","author":"Kroger A. T.","year":"2011","journal-title":"MMWR \u2010 Recommendations and Reports"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70552","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.70552","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:20:51Z","timestamp":1779189651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":45,"journal-issue":{"issue":"8-9","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/sim.70552"],"URL":"https:\/\/doi.org\/10.1002\/sim.70552","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70552"}}