{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:46:07Z","timestamp":1792601167713,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"23-24","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302882\/2022\u20107"],"award-info":[{"award-number":["302882\/2022\u20107"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["PQ\u201000787\u201021"],"award-info":[{"award-number":["PQ\u201000787\u201021"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["RED\u201000133\u201021"],"award-info":[{"award-number":["RED\u201000133\u201021"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sequential hypothesis testing has been used in randomized clinical trials and in monitoring adverse events after vaccination. Typically, the presumption is that all data that have been previously used in the sequential analysis remain the same, and only new data are added. We call this the \u201canchoring\u201d assumption. In prelicensing randomized trials, enrollment goals are set based on these sequential hypothesis tests so that a trial may stop if a drug proves either too hazardous or, conversely, so beneficial that it would be unethical to deny the treatment to others. However, in monitoring adverse events after vaccination, data are mostly \u201csecondary use,\u201d or real\u2010world data. That is, these data are not gathered for research, but are clinical data that have been repurposed for observational vaccine safety surveillance. As such, the counts of exposed persons and adverse events may be subject to revisions over time. These data changes directly challenge the anchoring assumption upon which most sequential hypothesis testing depends. If these data changes are discovered prior to subsequent hypothesis tests, it is unclear how to account for these changes in subsequent tests. We introduce a solution: \u201crobust alpha spending\u201d to protect overall type I error probability, statistical power, and surveillance time from low\u2010level data instability present in secondary use data sources used for adverse event monitoring.<\/jats:p>","DOI":"10.1002\/sim.70760","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:04:21Z","timestamp":1791554661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Robust Alpha Spending for Unstable Data"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-8924","authenticated-orcid":false,"given":"Ivair R.","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Population Medicine Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"},{"name":"Computer Department Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9900-2142","authenticated-orcid":false,"given":"Judith C.","family":"Maro","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18010080"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3966"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-1722I"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0b013e3180616c0a"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000155506.05636.a4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2307\/2336502"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177012099"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/64.2.191"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2307\/2530245"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531959"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/07474946.2011.539924"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5002"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.9094"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.13063\/2327\u20109214.1219"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3780"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2026.6190"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa543"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019\u20101808"},{"key":"e_1_2_10_20_1","unstructured":"I.SilvaandM.Kulldorff \u201cSequential: Exact Sequential Analysis for Poisson and Binomial Data. R Foundation for Statistical Computing\u2010 Contributed Packages; Vienna Austria \u201dR Package version 4.3.3 (2024)."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12324"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11009-017-9586-z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8097"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70760","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.70760","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70760","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:35:44Z","timestamp":1792600544000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":22,"journal-issue":{"issue":"23-24","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/sim.70760"],"URL":"https:\/\/doi.org\/10.1002\/sim.70760","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70760"}}