{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T01:03:03Z","timestamp":1768352583492,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here we present as case study how re\u2010randomization tests were performed in two randomized, controlled clinical trials as sensitivity analyses, as recommended by the United States Food and Drug Administration in the context of adaptive randomization. This was done to confirm primary conclusions on immunological noninferiority of an investigational new fully liquid presentation of a quadrivalent cross\u2010reacting material conjugate meningococcal vaccine (MenACWY\u2010CRM), over its licensed lyophilized\/liquid presentation. In two phase 2b studies (Study #1: NCT03652610; Study #2: NCT03433482), noninferiority of the fully liquid presentation of MenACWY\u2010CRM to the licensed presentation was assessed and demonstrated for immune responses against meningococcal serogroup A (MenA), the only vaccine component modified from lyophilized to liquid in the new presentation. The original vaccine assignment algorithm, with a minimization procedure accounting for center or center within age strata, was used to re\u2010randomize participants belonging to the fully liquid and licensed vaccine groups while keeping antibody responses, covariates and entry order as observed. Test statistics under re\u2010randomization were generated according to the ANCOVA model used in the primary analysis. To confirm immunological noninferiority following re\u2010randomization, the corresponding p\u2010values had to be &lt;0.025. For both studies and all primary objective evaluations, the re\u2010randomization p\u2010values were well below 0.025 (0.0004 for Study #1; 0.0001 for the two co\u2010primary endpoints in Study #2). Re\u2010randomization tests performed to comply with a regulatory request confirmed the primary conclusions of immunological noninferiority for the MenA of the fully liquid compared to the licensed vaccine presentation.<\/jats:p>","DOI":"10.1002\/pst.2290","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T04:20:07Z","timestamp":1674879607000},"page":"570-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Re\u2010randomization tests as sensitivity analyses to confirm immunological noninferiority of an investigational vaccine: Case study"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-2398","authenticated-orcid":false,"given":"Luca","family":"Grassano","sequence":"first","affiliation":[{"name":"Biostatistics GSK  Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Ranzato","sequence":"additional","affiliation":[{"name":"Biostatistics GSK  Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Clinical Research and Development Centre GSK  Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Costantini","sequence":"additional","affiliation":[{"name":"Biostatistics GSK  Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2018.1521280"},{"key":"e_1_2_9_3_1","unstructured":"EMA.Menveo summary of product charactersistics https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/menveo-epar-product-information_en.pdf2021."},{"key":"e_1_2_9_4_1","unstructured":"FDA.Menveo prescribing information http:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/Vaccines\/ApprovedProducts\/UCM201349.pdf2021."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.09.068"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2021.1981085"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12062"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/asq014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2017.1375934"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280220985564"},{"key":"e_1_2_9_11_1","article-title":"Statistical inference for vaccine efficacy: a re\u2010randomization procedure to analyse Poisson outcomes under covariate\u2010adaptive randomization","author":"Ovbude LJ","year":"2022","journal-title":"Stat Biopharm Res"},{"key":"e_1_2_9_12_1","unstructured":"EMA.Guideline on adjustment for baseline covariates in clinical trials. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-adjustment-baseline-covariates-clinical-trials_en.pdf2022."},{"key":"e_1_2_9_13_1","unstructured":"FDA.Adaptive designs for clinical trials of drugs and biologics https:\/\/www.fda.gov\/media\/78495\/download2021."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541\u20100420.2010.01545.x"},{"key":"e_1_2_9_15_1","unstructured":"WHO.Guidelines on clinical evaluation of vaccines: regulatory expectations https:\/\/www.who.int\/publications\/m\/item\/WHO-TRS-1004-web-annex-92022."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543400802527908"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1214\/088342304000000396"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.214"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8577"},{"key":"e_1_2_9_20_1","unstructured":"FDA.E9(R1) statistical principles for clinical trials: addendum: estimands and sensitivity analysis in clinical trials https:\/\/www.fda.gov\/media\/148473\/download2021."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1978.124"}],"container-title":["Pharmaceutical 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