{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:04:27Z","timestamp":1779782667214,"version":"3.53.1"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007226","name":"Villanova University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Contemporary Clinical Trials"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.cct.2025.108012","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:10:42Z","timestamp":1754665842000},"page":"108012","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Using multiple biomarkers for patient enrichment in two-stage clinical designs"],"prefix":"10.1016","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2736-2303","authenticated-orcid":false,"given":"Fengqing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5304-0530","authenticated-orcid":false,"given":"Jiangtao","family":"Gou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.cct.2025.108012_b1","doi-asserted-by":"crossref","first-page":"e141","DOI":"10.14694\/EdBook_AM.2015.35.e141","article-title":"Improving clinical trial efficiency: Thinking outside the box","volume":"35","author":"Mandrekar","year":"2015","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"issue":"Volume 8, 2021","key":"10.1016\/j.cct.2025.108012_b2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1146\/annurev-statistics-040720-032818","article-title":"Adaptive enrichment designs in clinical trials","volume":"8","author":"Thall","year":"2021","journal-title":"Annu. Rev. Stat. Appl."},{"issue":"5","key":"10.1016\/j.cct.2025.108012_b3","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1056\/NEJMra1510070","article-title":"Drug-development challenges for small biopharmaceutical companies","volume":"376","author":"Moscicki","year":"2017","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"10.1016\/j.cct.2025.108012_b4","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/10543406.2017.1379532","article-title":"On enrichment strategies for biomarker stratified clinical trials","volume":"28","author":"Wang","year":"2018","journal-title":"J. Biopharm. Statist."},{"issue":"2","key":"10.1016\/j.cct.2025.108012_b5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0197-2456(97)00118-9","article-title":"Threats to the validity of clinical trials employing enrichment strategies for sample selection","volume":"19","author":"Leber","year":"1998","journal-title":"Controlled Clin. Trials"},{"issue":"3","key":"10.1016\/j.cct.2025.108012_b6","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/biom.12461","article-title":"A predictive enrichment procedure to identify potential responders to a new therapy for randomized, comparative controlled clinical studies","volume":"72","author":"Li","year":"2015","journal-title":"Biometrics"},{"issue":"6","key":"10.1016\/j.cct.2025.108012_b7","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1164\/rccm.202009-3649ED","article-title":"Risk, results, and costs: Optimizing clinical trial efficiency through prognostic enrichment","volume":"203","author":"Viele","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.cct.2025.108012_b8","series-title":"Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products Guidance for Industry","author":"FDA","year":"2019"},{"issue":"4","key":"10.1016\/j.cct.2025.108012_b9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/biostatistics\/kxt010","article-title":"Adaptive enrichment designs for clinical trials","volume":"14","author":"Simon","year":"2013","journal-title":"Biostatistics"},{"issue":"27","key":"10.1016\/j.cct.2025.108012_b10","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.1002\/sim.7042","article-title":"An adaptive design for updating the threshold value of a continuous biomarker","volume":"35","author":"Spencer","year":"2016","journal-title":"Stat. Med."},{"key":"10.1016\/j.cct.2025.108012_b11","series-title":"Improving Inference for a Two-Stage Design with Application to Enrichment Designs","author":"Lin","year":"2020"},{"issue":"5","key":"10.1016\/j.cct.2025.108012_b12","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1214\/21-AOS2051","article-title":"Inference for a two-stage enrichment design","volume":"49","author":"Lin","year":"2021","journal-title":"Ann. Statist."},{"issue":"3","key":"10.1016\/j.cct.2025.108012_b13","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1111\/biom.13805","article-title":"Design considerations for two-stage enrichment clinical trials","volume":"79","author":"Frieri","year":"2023","journal-title":"Biometrics"},{"issue":"1","key":"10.1016\/j.cct.2025.108012_b14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/pst.1589","article-title":"Use of historical control data for assessing treatment effects in clinical trials","volume":"13","author":"Viele","year":"2014","journal-title":"Pharm. Stat."},{"issue":"1","key":"10.1016\/j.cct.2025.108012_b15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.2517-6161.1961.tb00408.x","article-title":"The moment generating function of the truncated multi-normal distribution","volume":"23","author":"Tallis","year":"1961","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"issue":"3","key":"10.1016\/j.cct.2025.108012_b16","first-page":"543","article-title":"Algorithm AS 249: Evaluation of the mean and covariance of the truncated multinormal distribution","volume":"38","author":"Leppard","year":"1989","journal-title":"J. R. Stat. Soc. Ser. C ( Appl. Statistics)"},{"issue":"2","key":"10.1016\/j.cct.2025.108012_b17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0165-1765(79)90111-3","article-title":"On the first and second moments of the truncated multi-normal distribution and a simple estimator","volume":"3","author":"Lee","year":"1979","journal-title":"Econom. Lett."},{"issue":"4","key":"10.1016\/j.cct.2025.108012_b18","first-page":"227","article-title":"A combined measure of cognition and function for clinical trials: The integrated Alzheimer\u2019s disease rating scale (iADRS)","volume":"2","author":"Wessels","year":"2015","journal-title":"J. Prev. Alzheimer\u2019 s Dis."},{"issue":"4","key":"10.1016\/j.cct.2025.108012_b19","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1212\/WNL.0000000000004860","article-title":"Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample","volume":"90","author":"La Joie","year":"2018","journal-title":"Neurology"},{"issue":"2","key":"10.1016\/j.cct.2025.108012_b20","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00259-018-4149-2","article-title":"Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer\u2019s disease in mild cognitive impairment patients","volume":"46","author":"Ciarmiello","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"issue":"1","key":"10.1016\/j.cct.2025.108012_b21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13195-020-00665-8","article-title":"Normalization of CSF pTau measurement by A\u03b240 improves its performance as a biomarker of Alzheimer\u2019s disease","volume":"12","author":"Guo","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"issue":"5","key":"10.1016\/j.cct.2025.108012_b22","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/acn3.51048","article-title":"The A4 study: \u03b2-amyloid and cognition in 4432 cognitively unimpaired adults","volume":"7","author":"Insel","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.cct.2025.108012_b23","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroimage.2022.119621","article-title":"Investigating the temporal pattern of neuroimaging-based brain age estimation as a biomarker for Alzheimer\u2019s disease related neurodegeneration","volume":"263","author":"Taylor","year":"2022","journal-title":"NeuroImage"},{"issue":"1","key":"10.1016\/j.cct.2025.108012_b24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.cct.2025.108012_b25","series-title":"Modelling Survival Data in Medical Research","author":"Collett","year":"2023"},{"issue":"5","key":"10.1016\/j.cct.2025.108012_b26","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/cpt.971","article-title":"Enrichment strategies in pediatric drug development: An analysis of trials submitted to the US food and drug administration","volume":"104","author":"Green","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.cct.2025.108012_b27","series-title":"Multiple Comparison Procedures","author":"Hochberg","year":"1987"},{"issue":"4","key":"10.1016\/j.cct.2025.108012_b28","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/biomet\/asu032","article-title":"A class of improved hybrid Hochberg-Hommel type step-up multiple test procedures","volume":"101","author":"Gou","year":"2014","journal-title":"Biometrika"},{"key":"10.1016\/j.cct.2025.108012_b29","series-title":"Handbook of Multiple Comparisons","first-page":"11","article-title":"Multiple test procedures based on p-values","author":"Tamhane","year":"2022"},{"issue":"28","key":"10.1016\/j.cct.2025.108012_b30","doi-asserted-by":"crossref","first-page":"5229","DOI":"10.1002\/sim.9909","article-title":"Sample size optimization for clinical trials using graphical approaches for multiplicity adjustment","volume":"42","author":"Zhang","year":"2023","journal-title":"Stat. Med."}],"container-title":["Contemporary Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S155171442500206X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S155171442500206X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:33:33Z","timestamp":1779780813000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S155171442500206X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":30,"alternative-id":["S155171442500206X"],"URL":"https:\/\/doi.org\/10.1016\/j.cct.2025.108012","relation":{},"ISSN":["1551-7144"],"issn-type":[{"value":"1551-7144","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Using multiple biomarkers for patient enrichment in two-stage clinical designs","name":"articletitle","label":"Article Title"},{"value":"Contemporary Clinical Trials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cct.2025.108012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"108012"}}