{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T18:56:01Z","timestamp":1769108161934,"version":"3.49.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":2844,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["088134\/Z\/09\/A"],"award-info":[{"award-number":["088134\/Z\/09\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["16 CVD 05"],"award-info":[{"award-number":["16 CVD 05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["088134\/Z\/09\/A"],"award-info":[{"award-number":["088134\/Z\/09\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["16 CVD 05"],"award-info":[{"award-number":["16 CVD 05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endpoints that are commonly used in trials of moderate\/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS\u2009\u2264\u20097) and assessed recurrent vascular events (stroke, transient ischaemic attack (TIA), ischemic heart disease (IHD)), modified Rankin Score (mRS) and cognitive testing with the Addenbrooke\u2019s Cognitive Examination (ACE-R) one year post-stroke. For a potential secondary prevention randomised controlled trial (RCT), we estimated sample sizes using individual or combined outcomes, at power 80% (and 90%), alpha 5%, required to detect a relative 10% risk reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Amongst 264 patients (118 lacunar, 146 non-lacunar), at one year, 30\/264 (11%) patients had a recurrent vascular event, 5 (2%) had died, 3 (1%) had clinically-diagnosed dementia, 53\/264 (20%) had mRS\u2009\u2265\u20093 and 29\/158 (19%) had ACE-R\u2009\u2264\u200982 (57 could not attend for cognitive testing). For a potential trial, at 80% power, using mRS\u2009\u2265\u20093 alone would require n\u2009&amp;gt;\u20095000 participants, recurrent vascular events alone n\u2009=\u20099908 participants, and a composite of any recurrent vascular event, ACE-R\u2009\u2264\u200982, dementia or mRS\u2009\u2265\u20092 (present in 56% of patients) n\u2009=\u20092224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/2396987317728854","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T05:45:44Z","timestamp":1504590344000},"page":"66-73","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8701-9043","authenticated-orcid":false,"given":"Stephen DJ","family":"Makin","sequence":"first","affiliation":[{"name":"Centre for Clinical Brain Sciences, Chancellors Building, Edinburgh, UK 1"},{"name":"Academic Section of Geriatric Medicine, 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