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One treatment may be most effective for some patients, while another may be most effective for others, and neither may be effective for another subset of patients. This potentially renders the conventional parallel group design highly inefficient. An attractive alternative is the N\u2010of\u20101 design, also called the multi\u2010crossover randomized controlled trial. In this design, each participant serves as their own control in a series of randomized blocks of treatment assignments. We propose novel designs for both the single\u2010person and multi\u2010person N\u2010of\u20101 trials that employ sequential monitoring. In particular, we allow for early stopping for a single participant as soon as there is sufficient evidence of a preferred treatment for them, and early stopping for the group of participants as soon as there is sufficient evidence of a preferred treatment for the population of patients. We provide sample size calculations and decision rules for terminating the trial early and illustrate their properties in simulation studies. We apply our proposed methods to N\u2010of\u20101 studies of brain tumor excisions and of methylphenidate in mild cognitive impairment.<\/jats:p>","DOI":"10.1002\/sim.70177","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T15:00:11Z","timestamp":1753110011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design and Analysis of N\u2010Of\u20101 Trials That Incorporate Sequential Monitoring"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-4838","authenticated-orcid":false,"given":"Shu","family":"Jiang","sequence":"first","affiliation":[{"name":"Division of Public Health Sciences Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Massachusetts Interdisciplinary Brain Center, Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3793-1437","authenticated-orcid":false,"given":"Rebecca A.","family":"Betensky","sequence":"additional","affiliation":[{"name":"Department of Biostatistics New York University School of Global Public Health  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Clinical Trials: A Methodologic Perspective","author":"Piantadosi S.","year":"2017"},{"key":"e_1_2_10_3_1","unstructured":"R.VeradhanandJ. 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