{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:07:51Z","timestamp":1780049271731,"version":"3.53.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["R01DK118354"],"award-info":[{"award-number":["R01DK118354"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>In clinical studies of chronic diseases, the effectiveness of an intervention is often assessed using \u201chigh cost\u201d outcomes that require long-term patient follow-up and\/or are invasive to obtain. While much progress has been made in the development of statistical methods to identify surrogate markers, that is, measurements that could replace such costly outcomes, they are generally not applicable to studies with a small sample size. These methods either rely on nonparametric smoothing which requires a relatively large sample size or rely on strict model assumptions that are unlikely to hold in practice and empirically difficult to verify with a small sample size. In this paper, we develop a novel rank-based nonparametric approach to evaluate a surrogate marker in a small sample size setting. The method developed in this paper is motivated by a small study of children with nonalcoholic fatty liver disease (NAFLD), a diagnosis for a range of liver conditions in individuals without significant history of alcohol intake. Specifically, we examine whether change in alanine aminotransferase (ALT; measured in blood) is a surrogate marker for change in NAFLD activity score (obtained by biopsy) in a trial, which compared Vitamin E ($n=50$) versus placebo ($n=46$) among children with NAFLD.<\/jats:p>","DOI":"10.1093\/biomtc\/ujad035","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T02:40:07Z","timestamp":1708656007000},"source":"Crossref","is-referenced-by-count":3,"title":["A rank-based approach to evaluate a surrogate marker in a small sample setting"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7288-1009","authenticated-orcid":false,"given":"Layla","family":"Parast","sequence":"first","affiliation":[{"name":"Department of Statistics and Data Science, University of Texas at Austin , Austin, TX 78712 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-2502","authenticated-orcid":false,"given":"Tianxi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard University , Boston, MA 02115 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-0169","authenticated-orcid":false,"given":"Lu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Stanford University , Stanford, CA 94305 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"2024022302395862800_bib1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1515\/jci-2012-0004","article-title":"A general algorithm for deciding transportability of experimental results","volume":"1","author":"Bareinboim","year":"2013","journal-title":"Journal of Causal Inference"},{"key":"2024022302395862800_bib2","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.2307\/2533853","article-title":"Criteria for the validation of surrogate endpoints in randomized experiments","volume":"54","author":"Buyse","year":"1998","journal-title":"Biometrics"},{"key":"2024022302395862800_bib3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/biostatistics\/kxt051","article-title":"Surrogacy assessment using principal stratification when surrogate and outcome measures are multivariate normal","volume":"15","author":"Conlon","year":"2014","journal-title":"Biostatistics"},{"key":"2024022302395862800_bib4","first-page":"181","article-title":"Non-parametric regression with censored survival time data","volume":"14","author":"Dabrowska","year":"1987","journal-title":"Scandinavian Journal of Statistics"},{"key":"2024022302395862800_bib5","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"2024022302395862800_bib6","doi-asserted-by":"crossref","first-page":"e2100354","DOI":"10.1002\/bimj.202100354","article-title":"Generalized pairwise comparisons for censored data: An overview","volume":"65","author":"Deltuvaite-Thomas","year":"2023","journal-title":"Biometrical Journal"},{"key":"2024022302395862800_bib7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrd3493","article-title":"Accelerating access to treatments for rare diseases","volume":"10","author":"Dunoyer","year":"2011","journal-title":"Nature Reviews Drug Discovery"},{"key":"2024022302395862800_bib8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1146\/annurev-statistics-032921-035359","article-title":"Surrogate endpoints in clinical trials","volume":"10","author":"Elliott","year":"2023","journal-title":"Annual Review of Statistics and its Application"},{"key":"2024022302395862800_bib9","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1214\/aos\/1176348900","article-title":"Variable bandwidth and local linear regression smoothers","volume":"20","author":"Fan","year":"1992","journal-title":"The Annals of Statistics"},{"key":"2024022302395862800_bib10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/sim.4780110204","article-title":"Statistical validation of intermediate endpoints for chronic diseases","volume":"11","author":"Freedman","year":"1992","journal-title":"Statistics in Medicine"},{"key":"2024022302395862800_bib11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","article-title":"The meaning and use of the area under a receiver operating characteristic (ROC) curve","volume":"143","author":"Hanley","year":"1982","journal-title":"Radiology"},{"key":"2024022302395862800_bib12","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1001\/jama.2011.520","article-title":"Effect of vitamin e or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the tonic randomized controlled trial","volume":"305","author":"Lavine","year":"2011","journal-title":"JAMA"},{"key":"2024022302395862800_bib13","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3390\/biomedicines9121915","article-title":"Metabolic fatty liver disease in children: A growing public health problem","volume":"9","author":"Le\u00a0Garf","year":"2021","journal-title":"Biomedicines"},{"key":"2024022302395862800_bib14","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/S0140-6736(08)60766-7","article-title":"The long-term effect of lifestyle interventions to prevent diabetes in the china da qing diabetes prevention study: a 20-year follow-up study","volume":"371","author":"Li","year":"2008","journal-title":"The Lancet"},{"key":"2024022302395862800_bib15","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0140-6736(06)69701-8","article-title":"Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the finnish diabetes prevention study","volume":"368","author":"Lindstr\u00f6m","year":"2006","journal-title":"The Lancet"},{"key":"2024022302395862800_bib16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a test of whether one of two random variables is stochastically larger than the other","volume":"18","author":"Mann","year":"1947","journal-title":"The Annals of Mathematical Statistics"},{"key":"2024022302395862800_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-6-49","article-title":"The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases","volume":"6","author":"Miyamoto","year":"2011","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"2024022302395862800_bib18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0197-2456(02)00236-2","article-title":"Statistical challenges in the evaluation of surrogate endpoints in randomized trials","volume":"23","author":"Molenberghs","year":"2002","journal-title":"Controlled Clinical Trials"},{"key":"2024022302395862800_bib19","article-title":"US National Library of Medicine: ClinicalTrials.gov: Semaglutide effects in obese youth with prediabetes\/new onset type 2 diabetes and non-alcoholic fatty liver disease","author":"NIH","year":"2022"},{"key":"2024022302395862800_bib20","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41575-019-0169-z","article-title":"Nafld in children: new genes, new diagnostic modalities and new drugs","volume":"16","author":"Nobili","year":"2019","journal-title":"Nature Reviews Gastroenterology and Hepatology"},{"key":"2024022302395862800_bib21","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1111\/biom.13067","article-title":"Using a surrogate marker for early testing of a treatment effect","volume":"75","author":"Parast","year":"2019","journal-title":"Biometrics"},{"key":"2024022302395862800_bib22","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/sim.6820","article-title":"Robust estimation of the proportion of treatment effect explained by surrogate marker information","volume":"35","author":"Parast","year":"2016","journal-title":"Statistics in Medicine"},{"key":"2024022302395862800_bib23","doi-asserted-by":"crossref","DOI":"10.1201\/9781315374161","volume-title":"Bioequivalence and Statistics in Clinical Pharmacology","author":"Patterson","year":"2017"},{"key":"2024022302395862800_bib24","doi-asserted-by":"crossref","DOI":"10.21236\/ADA557437","article-title":"Transportability across studies: A formal approach","author":"Pearl","year":"2011"},{"key":"2024022302395862800_bib25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/sim.4780080407","article-title":"Surrogate endpoints in clinical trials: definition and operational criteria","volume":"8","author":"Prentice","year":"1989","journal-title":"Statistics in Medicine"},{"key":"2024022302395862800_bib26","first-page":"31","article-title":"Conditional probability density and regression estimators","volume":"25","author":"Rosenblatt","year":"1969","journal-title":"Multivariate Analysis II"},{"key":"2024022302395862800_bib27","article-title":"The SurrogateRank package and repository","author":"SurrogateRank Repository","year":"2023"},{"key":"2024022302395862800_bib28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijar.2019.02.007","article-title":"Surrogate outcomes and transportability","volume":"108","author":"Tikka","year":"2019","journal-title":"International Journal of Approximate Reasoning"},{"key":"2024022302395862800_bib29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/biom.12071","article-title":"Surrogate measures and consistent surrogates","volume":"69","author":"VanderWeele","year":"2013","journal-title":"Biometrics"},{"key":"2024022302395862800_bib30","doi-asserted-by":"crossref","first-page":"6321","DOI":"10.1002\/sim.9185","article-title":"Quantifying the feasibility of shortening clinical trial duration using surrogate markers","volume":"40","author":"Wang","year":"2021","journal-title":"Statistics in Medicine"},{"key":"2024022302395862800_bib31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/biomet\/asz065","article-title":"Model-free approach to quantifying the proportion of treatment effect explained by a surrogate marker","volume":"107","author":"Wang","year":"2020","journal-title":"Biometrika"},{"key":"2024022302395862800_bib32","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/j.0006-341X.2002.00803.x","article-title":"A measure of the proportion of treatment effect explained by a surrogate marker","volume":"58","author":"Wang","year":"2002","journal-title":"Biometrics"},{"key":"2024022302395862800_bib33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/sim.4780080405","article-title":"Surrogate endpoints in clinical trials: cardiovascular diseases","volume":"8","author":"Wittes","year":"1989","journal-title":"Statistics in Medicine"}],"container-title":["Biometrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biometrics\/article-pdf\/80\/1\/ujad035\/56741252\/ujad035.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biometrics\/article-pdf\/80\/1\/ujad035\/56741252\/ujad035.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T02:40:25Z","timestamp":1708656025000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biometrics\/article\/doi\/10.1093\/biomtc\/ujad035\/7612597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,2,22]]},"published-print":{"date-parts":[[2024,1,29]]}},"URL":"https:\/\/doi.org\/10.1093\/biomtc\/ujad035","relation":{},"ISSN":["0006-341X","1541-0420"],"issn-type":[{"value":"0006-341X","type":"print"},{"value":"1541-0420","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2024,1,29]]},"article-number":"ujad035"}}