{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:03:49Z","timestamp":1791601429932,"version":"4.3.4"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011958","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["0134-00257B"],"award-info":[{"award-number":["0134-00257B"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R349-2020-835"],"award-info":[{"award-number":["R349-2020-835"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Kr\u00e6ftens Bek\u00e6mpelse","doi-asserted-by":"publisher","award":["R327-A19137"],"award-info":[{"award-number":["R327-A19137"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Kr\u00e6ftens Bek\u00e6mpelse","doi-asserted-by":"publisher","award":["KBVU-MS R320-A18526"],"award-info":[{"award-number":["KBVU-MS R320-A18526"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Aging Clin Exp Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Older adults and immunocompromised individulas are often excluded from vaccine trials.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Aim<\/jats:title>\n                <jats:p>We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (<jats:italic>n<\/jats:italic>\u2009=\u2009193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (<jats:italic>n<\/jats:italic>\u2009=\u2009129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020\u20132021 (only COVID-19 vaccine trials) (<jats:italic>p<\/jats:italic>\u2009=\u20090.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p\u2009=\u20090.058).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40520-023-02380-4","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T11:02:53Z","timestamp":1680865373000},"page":"917-923","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Exclusion of older adults and immunocompromised\u00a0individuals in influenza, pneumococcal and COVID-19 vaccine trials before and after the COVID-19 pandemic"],"prefix":"10.1007","volume":"35","author":[{"given":"Katrine","family":"Bukan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby","family":"Pearce-Slade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Eiberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna","family":"Yahav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Tuells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Epaulard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon G.","family":"Holler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper","family":"Roed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"S\u00f8borg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Ulrik St\u00e6hr","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-0095","authenticated-orcid":false,"given":"Zitta Barrella","family":"Harboe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"2380_CR1","doi-asserted-by":"publisher","first-page":"e1003","DOI":"10.1016\/S2214-109X(20)30264-3","volume":"8","author":"C Warren-Gash","year":"2020","unstructured":"Warren-Gash C, Perel P, Guthrie B et al (2020) Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. Lancet Glob Health 8:e1003\u2013e1017. https:\/\/doi.org\/10.1016\/S2214-109X(20)30264-3","journal-title":"Lancet Glob Health"},{"key":"2380_CR2","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1001\/jamainternmed.2020.5084","volume":"180","author":"BKI Helfand","year":"2020","unstructured":"Helfand BKI, Webb M, Gartaganis SL et al (2020) The exclusion of older persons from vaccine and treatment trials for coronavirus disease 2019-missing the target. JAMA Intern Med 180:1546\u20131549. https:\/\/doi.org\/10.1001\/jamainternmed.2020.5084","journal-title":"JAMA Intern Med"},{"key":"2380_CR3","doi-asserted-by":"publisher","first-page":"101455","DOI":"10.1016\/j.arr.2021.101455","volume":"71","author":"N Veronese","year":"2021","unstructured":"Veronese N, Petrovic M, Benetos A et al (2021) Underrepresentation of older adults in clinical trials on COVID-19 vaccines: a systematic review. Ageing Res Rev 71:101455. https:\/\/doi.org\/10.1016\/j.arr.2021.101455","journal-title":"Ageing Res Rev"},{"key":"2380_CR4","doi-asserted-by":"publisher","first-page":"afab282","DOI":"10.1093\/ageing\/afab282","volume":"51","author":"KH Pitkala","year":"2022","unstructured":"Pitkala KH, Strandberg TE (2022) Clinical trials in older people. Age Ageing 51:afab282. https:\/\/doi.org\/10.1093\/ageing\/afab282","journal-title":"Age Ageing"},{"key":"2380_CR5","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1001\/jama.2018.12368","volume":"320","author":"MA Bernard","year":"2018","unstructured":"Bernard MA, Clayton JA, Lauer MS (2018) Inclusion across the lifespan: NIH policy for clinical research. JAMA 320:1535\u20131536. https:\/\/doi.org\/10.1001\/jama.2018.12368","journal-title":"JAMA"},{"key":"2380_CR6","unstructured":"FDA Report (2014) FDA action plan to enhance the collection and availability of demographic subgroup data. https:\/\/www.fda.gov\/media\/89307\/download. Accessed 1 Feb 2023"},{"key":"2380_CR7","unstructured":"European Medicines Agency. Medicines for older people. https:\/\/www.ema.europa.eu\/en\/human-regulatory\/research-development\/medicines-older-people. Accessed 1 Feb 2023"},{"key":"2380_CR8","unstructured":"European Medicines Agencies search engine. Available at: https:\/\/www.ema.europa.eu\/en\/medicines. Accessed 1 Feb 2023"},{"key":"2380_CR9","unstructured":"U.S. Food and Drug Administration (FDA). Vaccines licensed for use in the United States. https:\/\/www.fda.gov\/vaccines-blood-biologics\/vaccines\/vaccines-licensed-use-united-states. Accessed 1 Feb 2023"},{"key":"2380_CR10","unstructured":"World Health Organization (2017) Guidelines on clinical evaluation of vaccines: regulatory expectations, Annex 9, TRS No 1004. https:\/\/www.who.int\/publications\/m\/item\/clinical-evaluation-of-vaccines-annex-9-trs-no-1004. Accessed 1 Feb 2023"},{"key":"2380_CR11","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research (2011) Guidance for Industry General Principles for the Development of Vaccines to Protect Against Global Infectious Diseases. Availabl. n.d."},{"key":"2380_CR12","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.smim.2018.10.010.1","volume":"40","author":"A Ciabattini","year":"2018","unstructured":"Ciabattini A, Nardini C, Santoro F et al (2018) Vaccination in the elderly: the challenge of immune changes with aging. Semin Immunol 40:83\u201394. https:\/\/doi.org\/10.1016\/j.smim.2018.10.010.1","journal-title":"Semin Immunol"},{"key":"2380_CR13","unstructured":"Reuters UK regulators say extra AstraZeneca vaccine data highlights efficacy in elderly. 2021. https:\/\/www.reuters.com\/world\/uk\/uk-regulators-say-extra-astrazeneca-vaccine-data-highlights-efficacy-elderly-2021-02-05\/. Accessed 1 Feb 2023"}],"container-title":["Aging Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-023-02380-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40520-023-02380-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-023-02380-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T07:27:46Z","timestamp":1683012466000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40520-023-02380-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":13,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["2380"],"URL":"https:\/\/doi.org\/10.1007\/s40520-023-02380-4","relation":{},"ISSN":["1720-8319"],"issn-type":[{"value":"1720-8319","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]},"assertion":[{"value":"4 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest. Some of the results of this study were presented at the ESCMID educational workshop on \u201cVaccination of the elderly in COVID-19 times\u201d, held on September 12\u201313, 2022, in Venice, Italy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Because the study was a literature review, ethical approval and informed consent were not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and informed consent"}}]}}