{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T18:41:58Z","timestamp":1771267318737,"version":"3.50.1"},"reference-count":65,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100006093","name":"Patient-Centered Outcomes Research Institute","doi-asserted-by":"publisher","award":["ME-1502-27794"],"award-info":[{"award-number":["ME-1502-27794"]}],"id":[{"id":"10.13039\/100006093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["R36HS028373-01"],"award-info":[{"award-number":["R36HS028373-01"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["K99CA287059"],"award-info":[{"award-number":["K99CA287059"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stat Methods Med Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>In multicenter randomized trials, when effect modifiers have a different distribution across centers, comparisons between treatment groups that average (standardize) effects over centers may not apply to any of the populations underlying the individual centers. In the presence of such heterogeneity, interpreting the evidence produced by a multicenter trial in the context of the local population underlying each center may be necessary. Here, we identify center-specific effects under conditions that are largely supported by the study design and are weaker than those underlying popular methods for the analysis of multicenter studies, in the presence of associations between center membership and the outcome (\u201ccenter-outcome associations\u201d conditional on baseline covariates and treatment). We then consider an additional testable condition of \u201cno center-outcome associations,\u201d given baseline covariates and treatment. We propose methods for estimating center-specific average treatment effects, when center-outcome associations are present and when they are absent. When center-outcome associations are absent, we discuss how the proposed methods are often more efficient and make weaker conditions than related transportability methods applied to multicenter trials. We evaluate the performance of the methods in a simulation study and illustrate their implementation using data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial.<\/jats:p>","DOI":"10.1177\/09622802251380624","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:11:45Z","timestamp":1761070305000},"page":"2330-2347","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Center-specific causal inference with multicenter trials\u2014Interpreting trial evidence in the context of each participating center"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8973-8655","authenticated-orcid":false,"given":"Sarah E.","family":"Robertson","sequence":"first","affiliation":[{"name":"CAUSALab, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon A.","family":"Steingrimsson","sequence":"additional","affiliation":[{"name":"Brown University School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina R.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Brown University School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Stuart","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-9931","authenticated-orcid":false,"given":"Issa J.","family":"Dahabreh","sequence":"additional","affiliation":[{"name":"CAUSALab, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"e_1_3_3_2_2","first-page":"270","article-title":"An applied researcher\u2019s guide to estimating effects from multisite individually randomized trials: Estimands, estimators, and estimates","volume":"1","author":"Miratrix L","unstructured":"Miratrix L, Weiss MJ, Henderson B. An applied researcher\u2019s guide to estimating effects from multisite individually randomized trials: Estimands, estimators, and estimates. J Res Educ Eff 2021; 1: 270\u2013283.","journal-title":"J Res Educ Eff"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.00569.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90034-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1037\/1082-989X.5.2.199"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.3424"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001177"},{"key":"e_1_3_3_8_2","article-title":"Detecting anomalies among practice sites within multicenter trials: an application of transportability methods to the topcat and accord bp trials","volume":"12","author":"Berkowitz SA","year":"2019","unstructured":"Berkowitz SA, Rudolph KE, Basu S. Detecting anomalies among practice sites within multicenter trials: an application of transportability methods to the topcat and accord bp trials. Circul: Cardiov Quality Outcomes 2019; 12: e004907.","journal-title":"Circul: Cardiov Quality Outcomes"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/pam.22154"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2022.11.008"},{"key":"e_1_3_3_11_2","volume-title":"Statistical issues in drug development","author":"Senn SS","year":"2008","unstructured":"Senn SS. Statistical issues in drug development, Vol. 69. \u00a0Chichester, UK.: John Wiley & Sons, 2008."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980815\/30)17:15\/16<1779::AID-SIM979>3.0.CO;2-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780100604"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-985X.2008.00552.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181caeb90"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000774"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwaa270"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1037\/h0037350"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1986.10478354"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2000.10474214"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13009"},{"key":"e_1_3_3_22_2","volume-title":"Causal inference: what if","author":"Hern\u00e1n MA","year":"2020","unstructured":"Hern\u00e1n MA, Robins JM. Causal inference: what if. Vol. 2020. Boca Raton: Chapman & Hill\/CRC Press, 2020."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181bd5638"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3182109296"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1515\/jci-2012-0002"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001231"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/28.1.1"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj127"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-13-58"},{"key":"e_1_3_3_30_2","unstructured":"Alene M Vansteelandt S Van Lancker K. Analyzing multi-center randomized trials with covariate adjustment while accounting for clustering. arXiv preprint arXiv:2504.12760 2025."},{"key":"e_1_3_3_31_2","first-page":"1111","article-title":"From SATE to PATT: combining experimental with observational studies to estimate population treatment effects","volume":"10","author":"Hartman E","year":"2013","unstructured":"Hartman E, Grieve R, Ramsahai R, et al. From SATE to PATT: combining experimental with observational studies to estimate population treatment effects. J R Stat Soc Ser A (Stat Soc) 2013; 10: 1111.","journal-title":"J R Stat Soc Ser A (Stat Soc)"},{"key":"e_1_3_3_32_2","unstructured":"Lu Y Scharfstein DO Brooks MM et al. Causal inference for comprehensive cohort studies. arXiv preprint arXiv:1910.03531 2019."},{"key":"e_1_3_3_33_2","unstructured":"Dahabreh IJ Steingrimsson JA Robins JM et al. Randomized trials and their observational emulations: a framework for benchmarking and joint analysis. arXiv preprint arXiv:2203.14857 2022."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1214\/19-AOS1857"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-7152(93)90167-H"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1056562466"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/07474930600972590"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/rssb.12299"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1903"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6507"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001097"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2005.00377.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511790942"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980815\/30)17:15\/16<1753::AID-SIM977>3.0.CO;2-X"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1257\/aer.p20171038"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21700-0"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1198\/000313002753631330"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1201\/9780429246593"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.3576"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/9781118625590"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198524847.001.0001"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8426"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/rssb.12213"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707615"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v092.i02"},{"key":"e_1_3_3_56_2","first-page":"20","article-title":"mgcv: GAMs and generalized ridge regression for R","volume":"1","author":"Wood SN","year":"2001","unstructured":"Wood SN. mgcv: GAMs and generalized ridge regression for R. R News 2001; 1: 20\u201325.","journal-title":"R News"},{"key":"e_1_3_3_57_2","first-page":"1905","article-title":"Statistical principles for clinical trials. International conference on harmonisation E9 expert working group","volume":"18","author":"Guideline IH","year":"1999","unstructured":"Guideline IH. Statistical principles for clinical trials. International conference on harmonisation E9 expert working group. Stat Med 1999; 18: 1905\u20131942.","journal-title":"Stat Med"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.1030"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1510057"},{"key":"e_1_3_3_60_2","volume-title":"The learning healthcare system: workshop summary","author":"Olsen L","year":"2007","unstructured":"Olsen L, Aisner D, McGinnis JM. The learning healthcare system: workshop summary. Washington, D.C.: National Academies Press (US), 2007."},{"key":"e_1_3_3_61_2","volume-title":"Social experiments: evaluating public programs with experimental methods","author":"Orr LL","year":"1999","unstructured":"Orr LL. Social experiments: evaluating public programs with experimental methods. Thousand Oaks, CA: Sage, 1999."},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/ev.20212"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/pst.438"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2956"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2021.1981338"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13716"}],"container-title":["Statistical Methods in Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09622802251380624","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09622802251380624","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09622802251380624","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:31:50Z","timestamp":1764772310000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09622802251380624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":65,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1177\/09622802251380624"],"URL":"https:\/\/doi.org\/10.1177\/09622802251380624","relation":{},"ISSN":["0962-2802","1477-0334"],"issn-type":[{"value":"0962-2802","type":"print"},{"value":"1477-0334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}