{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:36:46Z","timestamp":1790030206095,"version":"4.0.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA"},{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.<\/jats:p>","DOI":"10.1038\/s41541-024-00937-6","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T14:24:52Z","timestamp":1731335092000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-767X","authenticated-orcid":false,"given":"Julie","family":"Dud\u00e1\u0161ov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-9764","authenticated-orcid":false,"given":"Zden\u011bk","family":"Valenta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-558X","authenticated-orcid":false,"given":"Jeffrey R.","family":"Sachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"937_CR1","doi-asserted-by":"crossref","unstructured":"Halloran, M. E., Longini Jr., I. M. & Struchiner, C. J. Design and Analysis of Vaccine Studies 1\u201318 (Springer, 2010).","DOI":"10.1007\/978-0-387-68636-3_1"},{"key":"937_CR2","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1002\/sim.1296","volume":"21","author":"SJ Pocock","year":"2002","unstructured":"Pocock, S. J., Assmann, S. E., Enos, L. E. & Kasten, L. E. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat. Med. 21, 2917\u20132930 (2002).","journal-title":"Stat. Med."},{"key":"937_CR3","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1002\/sim.6507","volume":"34","author":"E Colantuoni","year":"2015","unstructured":"Colantuoni, E. & Rosenblum, M. Leveraging prognostic baseline variables to gain precision in randomized trials. Stat. Med. 34, 2602\u20132617 (2015).","journal-title":"Stat. Med."},{"key":"937_CR4","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1111\/biom.13377","volume":"77","author":"D Benkeser","year":"2021","unstructured":"Benkeser, D. et al. Improving precision and power in randomized trials for COVID-19 treatments using covariate adjustment, for binary, ordinal, and time-to-event outcomes. Biometrics 77, 1467\u20131481 (2021).","journal-title":"Biometrics"},{"key":"937_CR5","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for industry: Adjusting for covariates in randomized clinical trials for drugs and biological products. (2023)."},{"key":"937_CR6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1093\/oxfordjournals.aje.a116498","volume":"136","author":"ME Halloran","year":"1992","unstructured":"Halloran, M. E., Haber, M. & Longini, I. M. Jr. Interpretation and estimation of vaccine efficacy under heterogeneity. Am. J. Epidemiol. 136, 328\u2013343 (1992).","journal-title":"Am. J. Epidemiol."},{"key":"937_CR7","doi-asserted-by":"crossref","unstructured":"Plotkin, S. A. & Gilbert, P. B. Correlates of protection. Plotkin\u2019s Vaccines 7th edn, 35\u201340 (Elsevier, 2017).","DOI":"10.1016\/B978-0-323-35761-6.00003-1"},{"key":"937_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00377-6","volume":"6","author":"J Dudasova","year":"2021","unstructured":"Dudasova, J. et al. A method to estimate probability of disease and vaccine efficacy from clinical trial immunogenicity data. NPJ Vaccines 6, 133 (2021).","journal-title":"NPJ Vaccines"},{"key":"937_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-024-02197-3","volume":"24","author":"J Dudasova","year":"2024","unstructured":"Dudasova, J., Valenta, Z. & Sachs, J. R. Elucidating vaccine efficacy using a correlate of protection, demographics, and logistic regression. BMC Med. Res. Methodol. 24, 101 (2024).","journal-title":"BMC Med. Res. Methodol."},{"key":"937_CR10","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1002\/sim.2282","volume":"25","author":"AJ Dunning","year":"2006","unstructured":"Dunning, A. J. A model for immunological correlates of protection. Stat. Med. 25, 1485\u20131497 (2006).","journal-title":"Stat. Med."},{"key":"937_CR11","doi-asserted-by":"publisher","first-page":"841","DOI":"10.4161\/hv.6.10.12636","volume":"6","author":"L Coudeville","year":"2010","unstructured":"Coudeville, L., Andre, P., Bailleux, F., Weber, F. & Plotkin, S. A new approach to estimate vaccine efficacy based on immunogenicity data applied to influenza vaccines administered by the intradermal or intramuscular routes. Hum. Vaccine 6, 841\u2013848 (2010).","journal-title":"Hum. Vaccine"},{"key":"937_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-015-0096-9","volume":"15","author":"AJ Dunning","year":"2015","unstructured":"Dunning, A. J., Kensler, J., Coudeville, L. & Bailleux, F. Some extensions in continuous models for immunological correlates of protection. BMC Med. Res. Methodol. 15, 107 (2015).","journal-title":"BMC Med. Res. Methodol."},{"key":"937_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-019-0687-y","volume":"19","author":"A Callegaro","year":"2019","unstructured":"Callegaro, A. & Tibaldi, F. Assessing correlates of protection in vaccine trials: statistical solutions in the context of high vaccine efficacy. BMC Med. Res. Methodol. 19, 47 (2019).","journal-title":"BMC Med. Res. Methodol."},{"key":"937_CR14","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1002\/bimj.202100015","volume":"63","author":"A Callegaro","year":"2021","unstructured":"Callegaro, A., Zahaf, T. & Tibaldi, F. Assurance in vaccine efficacy clinical trial design based on immunological responses. Biom. J. 63, 1347\u20131547 (2021).","journal-title":"Biom. J."},{"key":"937_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-10-18","volume":"10","author":"L Coudeville","year":"2010","unstructured":"Coudeville, L. et al. Relationship between haemagglutinationinhibiting antibody titres and clinical protection against influenza: development and application of a Bayesian random-effects model. BMC Med. Res. Methodol. 10, 18 (2010).","journal-title":"BMC Med. Res. Methodol."},{"key":"937_CR16","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1097\/INF.0b013e3182367662","volume":"30","author":"S Black","year":"2011","unstructured":"Black, S. et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr. Infect. Dis. J. 30, 1081\u20131085 (2011).","journal-title":"Pediatr. Infect. Dis. J."},{"key":"937_CR17","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1080\/21645515.2015.1118595","volume":"12","author":"P Jin","year":"2016","unstructured":"Jin, P. et al. Validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6\u201335 months. Hum. Vaccine Imunother. 12, 916\u2013921 (2016).","journal-title":"Hum. Vaccine Imunother."},{"key":"937_CR18","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1080\/14760584.2017.1335603","volume":"16","author":"W Zhu","year":"2017","unstructured":"Zhu, W., Jin, P., Li, J.-X., Zhu, F.-C. & Liu, P. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints. Expert Rev. Vaccines 16, 945\u2013949 (2017).","journal-title":"Expert Rev. Vaccines"},{"key":"937_CR19","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1016\/j.vaccine.2021.02.074","volume":"39","author":"MA Habib","year":"2021","unstructured":"Habib, M. A. et al. Correlation of protection against varicella in a randomized Phase III varicella-containing vaccine efficacy trial in healthy infants. Vaccine 39, 3445\u20133454 (2021).","journal-title":"Vaccine"},{"key":"937_CR20","unstructured":"Dudasova, J. vaxpmx, R package, https:\/\/cran.r-project.org\/web\/packages\/vaxpmx\/index.html (2024)."},{"key":"937_CR21","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1056\/NEJMoa051016","volume":"352","author":"MN Oxman","year":"2005","unstructured":"Oxman, M. N. et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N. Engl. J. Med. 352, 2271\u20132284 (2005).","journal-title":"N. Engl. J. Med."},{"key":"937_CR22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1056\/NEJMoa1800820","volume":"379","author":"S Sridhar","year":"2018","unstructured":"Sridhar, S. et al. Effect of dengue serostatus on dengue vaccine safety and efficacy. N. Engl. J. Med. 379, 327\u2013340 (2018).","journal-title":"N. Engl. J. Med."},{"key":"937_CR23","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1080\/21645515.2019.1658503","volume":"15","author":"SJ Thomas","year":"2019","unstructured":"Thomas, S. J. & Yoon, I.-K. A review of Dengvaxia\u00ae: development to deployment. Hum. Vaccines Immunother. 15, 2295\u20132314 (2019).","journal-title":"Hum. Vaccines Immunother."},{"key":"937_CR24","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/sim.4780080407","volume":"8","author":"RL Prentice","year":"1989","unstructured":"Prentice, R. L. Surrogate endpoints in clinical trials: definition and operational criteria. Stat. Med. 8, 431\u2013440 (1989).","journal-title":"Stat. Med."},{"key":"937_CR25","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1086\/528696","volume":"197","author":"MJ Levin","year":"2008","unstructured":"Levin, M. J. et al. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J. Infect. Dis. 197, 825\u2013835 (2008).","journal-title":"J. Infect. Dis."},{"key":"937_CR26","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1093\/infdis\/jiu279","volume":"210","author":"PB Gilbert","year":"2014","unstructured":"Gilbert, P. B. et al. Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve. J. Infect. Dis. 210, 1573\u20131581 (2014).","journal-title":"J. Infect. Dis."},{"key":"937_CR27","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1214\/aos\/1176344136","volume":"6","author":"G Schwarz","year":"1978","unstructured":"Schwarz, G. Estimating the dimension of a model. Ann. Stat. 6, 461\u2013464 (1978).","journal-title":"Ann. Stat."},{"key":"937_CR28","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1093\/biomet\/69.1.239","volume":"69","author":"D Schoenfeld","year":"1982","unstructured":"Schoenfeld, D. Partial residuals for the proportional hazards regression model. Biometrika 69, 239\u2013241 (1982).","journal-title":"Biometrika"},{"key":"937_CR29","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1038\/s41591-021-01392-9","volume":"27","author":"H Salje","year":"2021","unstructured":"Salje, H. et al. Evaluation of the extended efficacy of the Dengvaxia vaccine against symptomatic and subclinical dengue infection. Nat. Med. 27, 1395\u20131400 (2021).","journal-title":"Nat. Med."},{"key":"937_CR30","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1016\/S0140-6736(14)61060-6","volume":"384","author":"MR Capeding","year":"2014","unstructured":"Capeding, M. R. et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet 384, 1358\u20131365 (2014).","journal-title":"Lancet"},{"key":"937_CR31","doi-asserted-by":"crossref","unstructured":"Therneau, T. M. & Grambsch, P. M. Modeling Survival Data: Extending the Cox Model. (Springer-Verlag, 2000).","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"937_CR32","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1161\/CIRCULATIONAHA.115.017719","volume":"133","author":"PC Austin","year":"2016","unstructured":"Austin, P. C., Lee, D. S. & Fine, J. P. Introduction to the analysis of survival data in the presence of competing risks. Circulation 133, 601\u2013609 (2016).","journal-title":"Circulation"},{"key":"937_CR33","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","volume":"94","author":"JP Fine","year":"1999","unstructured":"Fine, J. P. & Gray, R. J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496\u2013509 (1999).","journal-title":"J. Am. Stat. Assoc."},{"key":"937_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003230","volume":"8","author":"D Buddhari","year":"2014","unstructured":"Buddhari, D. et al. Dengue virus neutralizing antibody levels associated with protection from infection in Thai cluster studies. PLoS Negl. Trop. Dis. 8, e3230 (2014).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"937_CR35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI147066","volume":"131","author":"S Henein","year":"2021","unstructured":"Henein, S. et al. Dengue vaccine breakthrough infections reveal properties of neutralizing antibodies linked to Protection. J. Clin. Invest. 131, e147066 (2021).","journal-title":"J. Clin. Invest."},{"key":"937_CR36","doi-asserted-by":"publisher","first-page":"1081107","DOI":"10.3389\/fimmu.2022.1081107","volume":"13","author":"SA Plotkin","year":"2023","unstructured":"Plotkin, S. A. Recent updates on correlates of vaccine-induced protection. Front. Immunol. 13, 1081107 (2023).","journal-title":"Front. Immunol."},{"key":"937_CR37","unstructured":"James, G., Witten, D., Hastie, T. & Tibshirani, R. An Introduction to Statistical Learning 101\u2013114 (Springer, 2017)."},{"key":"937_CR38","doi-asserted-by":"publisher","first-page":"5912","DOI":"10.1016\/j.vaccine.2022.08.055","volume":"40","author":"L Qi","year":"2022","unstructured":"Qi, L. et al. Neutralizing antibody correlates of sequence specific dengue disease in a tetravalent dengue vaccine efficacy trial in Asia. Vaccine 40, 5912\u20135923 (2022).","journal-title":"Vaccine"},{"key":"937_CR39","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1411037","volume":"372","author":"L Villar","year":"2015","unstructured":"Villar, L. et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N. Engl. J. Med. 372, 113\u2013123 (2015).","journal-title":"N. Engl. J. Med."},{"key":"937_CR40","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1016\/S0140-6736(12)61428-7","volume":"380","author":"A Sabchareon","year":"2012","unstructured":"Sabchareon, A. et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet 380, 1559\u20131567 (2012).","journal-title":"Lancet"},{"key":"937_CR41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.0006-341X.2002.00021.x","volume":"58","author":"CE Frangakis","year":"2002","unstructured":"Frangakis, C. E. & Rubin, D. B. Principal stratification in causal inference. Biometrics 58, 21\u201329 (2002).","journal-title":"Biometrics"},{"key":"937_CR42","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1111\/j.1541-0420.2006.00569.x","volume":"62","author":"D Follmann","year":"2006","unstructured":"Follmann, D. Augmented designs to assess immune response in vaccine trials. Biometrics 62, 1161\u20131170 (2006).","journal-title":"Biometrics"},{"key":"937_CR43","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1111\/biom.13375","volume":"77","author":"NS Hejazi","year":"2021","unstructured":"Hejazi, N. S., van der Laan, M. J., Janes, H. E., Gilbert, P. B. & Benkeser, D. C. Efficient nonparametric inference on the effects of stochastic interventions under two-phase sampling, with applications to vaccine efficacy trials. Biometrics 77, 1241\u20131253 (2021).","journal-title":"Biometrics"},{"key":"937_CR44","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","volume":"27","author":"DS Khoury","year":"2021","unstructured":"Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205\u20131211 (2021).","journal-title":"Nat. Med."},{"key":"937_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103651","volume":"73","author":"BM Maas","year":"2021","unstructured":"Maas, B. M. et al. Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis. EBioMedicine 73, 103651 (2021).","journal-title":"EBioMedicine"},{"key":"937_CR46","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1126\/science.abm3425","volume":"375","author":"PB Gilbert","year":"2022","unstructured":"Gilbert, P. B. et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science 375, 43\u201350 (2022).","journal-title":"Science"},{"key":"937_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104264","volume":"84","author":"B Kandala","year":"2022","unstructured":"Kandala, B. et al. Accelerating model-informed decisions for COVID-19 vaccine candidates using a model-based meta-analysis approach. EBioMedicine 84, 104264 (2022).","journal-title":"EBioMedicine"},{"key":"937_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-022-00538-1","volume":"7","author":"J Ryman","year":"2022","unstructured":"Ryman, J. et al. Predicting vaccine effectiveness against invasive pneumococcal disease in children using immunogenicity data. NPJ Vaccines 7, 140 (2022).","journal-title":"NPJ Vaccines"},{"key":"937_CR49","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41591-023-02228-4","volume":"29","author":"DS Khoury","year":"2023","unstructured":"Khoury, D. S. et al. Predicting the efficacy of variant-modified COVID-19 vaccine boosters. Nat. Med. 29, 574\u2013578 (2023).","journal-title":"Nat. Med."},{"key":"937_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48180-w","volume":"15","author":"MT Berry","year":"2024","unstructured":"Berry, M. T. et al. Predicting vaccine effectiveness for mpox. Nat. Commun. 15, 3856 (2024).","journal-title":"Nat. Commun."},{"key":"937_CR51","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3390\/vaccines11040806","volume":"11","author":"M Stoddard","year":"2023","unstructured":"Stoddard, M. et al. Heterogeneity in vaccinal immunity to SARS-CoV-2 can be addressed by a personalized booster strategy. Vaccines 11, 806 (2023).","journal-title":"Vaccines"},{"key":"937_CR52","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1214\/aos\/1176344247","volume":"6","author":"O Aalen","year":"1978","unstructured":"Aalen, O. Nonparametric inference for a family of counting processes. Ann. Stat. 6, 701\u2013726 (1978).","journal-title":"Ann. Stat."},{"key":"937_CR53","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1080\/01621459.1992.10476248","volume":"87","author":"RJ Gray","year":"1992","unstructured":"Gray, R. J. Flexible methods for analyzing survival data using splines, with applications to breast cancer prognosis. J. Am. Stat. Assoc. 87, 942\u2013951 (1992).","journal-title":"J. Am. Stat. Assoc."},{"key":"937_CR54","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/1467-9469.00065","volume":"29","author":"TH Scheike","year":"2002","unstructured":"Scheike, T. H. & Zhang, M.-J. An additive-multiplicative Cox-Aalen regression model. Scand. J. Stat. 29, 75\u201388 (2002).","journal-title":"Scand. J. Stat."},{"key":"937_CR55","doi-asserted-by":"publisher","first-page":"285","DOI":"10.4049\/jimmunol.99.2.285","volume":"99","author":"PK Russell","year":"1967","unstructured":"Russell, P. K., Nisalak, A., Sukhavachana, P. & Vivona, S. A plaque reduction test for dengue virus neutralizing antibodies. J. Immunol. 99, 285\u2013290 (1967).","journal-title":"J. Immunol."},{"key":"937_CR56","doi-asserted-by":"publisher","first-page":"825","DOI":"10.4269\/ajtmh.2009.08-0625","volume":"81","author":"SJ Thomas","year":"2009","unstructured":"Thomas, S. J. et al. Dengue plaque reduction neutralization test (PRNT) in primary and secondary dengue virus infections: how alterations in assay conditions impact performance. Am. J. Trop. Med. Hyg. 81, 825\u2013833 (2009).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"937_CR57","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1086\/522428","volume":"196","author":"L Qin","year":"2007","unstructured":"Qin, L., Gilbert, P. B., Corey, L., McElrath, M. J. & Self, S. G. A framework for assessing immunological correlates of protection in vaccine trials. J. Infect. Dis. 196, 1304\u20131312 (2007).","journal-title":"J. Infect. Dis."},{"key":"937_CR58","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","volume":"34","author":"DR Cox","year":"1972","unstructured":"Cox, D. R. Regression models and life-tables (with discussion). J. R. Stat. Soc. Ser. B 34, 187\u2013220 (1972).","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"937_CR59","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","volume":"19","author":"H Akaike","year":"1974","unstructured":"Akaike, H. A new look at the statistical model identification. IEEE Trans. Autom. Control 19, 716\u2013723 (1974).","journal-title":"IEEE Trans. Autom. Control"},{"key":"937_CR60","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/sim.3503","volume":"28","author":"PB Gilbert","year":"2009","unstructured":"Gilbert, P. B., Qin, L. & Self, S. G. Response to Andrew Dunning\u2019s comment on \u2018Evaluating a surrogate endpoint at three levels, with application to vaccine development\u2019. Stat. Med. 28, 716\u2013719 (2009).","journal-title":"Stat. Med."},{"key":"937_CR61","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1111\/bcp.13577","volume":"84","author":"XS Xu","year":"2018","unstructured":"Xu, X. S. et al. Full covariate modelling approach in population pharmacokinetics: understanding the underlying hypothesis tests and implications of multiplicity. Br. J. Clin. Pharmacol. 84, 1525\u20131534 (2018).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"937_CR62","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/S0140-6736(21)02183-8","volume":"398","author":"SY Tartof","year":"2021","unstructured":"Tartof, S. Y. et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet 398, 1407\u20131416 (2021).","journal-title":"Lancet"},{"key":"937_CR63","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1038\/sj.bjc.6602102","volume":"91","author":"JM Satagopan","year":"2004","unstructured":"Satagopan, J. M. et al. A note on competing risks in survival data analysis. Br. J. Cancer 91, 1229\u20131235 (2004).","journal-title":"Br. J. Cancer"}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-024-00937-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-024-00937-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-024-00937-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T07:05:45Z","timestamp":1731395145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-024-00937-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["937"],"URL":"https:\/\/doi.org\/10.1038\/s41541-024-00937-6","relation":{},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]},"assertion":[{"value":"8 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.D. is an employee of MSD Czech Republic s.r.o., Prague, Czech Republic, and J.R.S. is an employee of Merck Sharp & Dohme LLC, subsidiaries of Merck & Co., Inc., Rahway, NJ, USA. J.D. and J.R.S. own stock in Merck & Co., Inc., Rahway, NJ, USA. Z.V. has no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"214"}}