{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:36:27Z","timestamp":1790688987069,"version":"4.1.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Large randomized trials are the best method to test the efficacy and safety of treatments expected to have moderate effects. We observed a significant decline in potential participants\u2019 response to mailed invitations to participate in such trials over a 10-year period and investigated possible reasons behind this and potential modifications to the invitation process to mitigate it.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Participants who declined to participate in the HPS2-THRIVE trial were asked to give a reason. Formal focus groups were conducted to explore the reasons that potential participants might have for not participating. In addition, two embedded randomized comparisons around the timing of provision of the full participant information leaflet (PIL) and its style were conducted during recruitment into this large randomized trial. HPS2-THRIVE is registered at ClinicalTrials.gov (NCT00461630).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The commonest reason given for declining invitations related to mobility and transportation (despite the offer of travel expenses). Both the focus groups and potential participants who declined their invitation indicated concern about side-effects of the treatment (as presented in the PIL) as a reason for declining the invitation. Neither delaying provision of the full PIL until the potential participant attended the trial clinic, nor modifying the style of the PIL improved the proportion of potential participants entering the trial: odds ratio (OR) 1.05 (95% confidence interval (CI) 0.94\u20131.17) and 1.10 (95% CI 0.94\u20131.28), respectively. However, modifying the style of the PIL did increase the proportion of participants attending screening appointments (OR 1.17, 95% CI 1.03\u20131.33).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Many reasons given for not participating in trials are not tractable to individual trials. However, modification of the PIL does show potential to modestly improve participation. If further trials could identify similar simple interventions that were beneficial, their net effects could substantially improve trial participation and facilitate recruitment into large trials.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-019-3779-4","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T18:02:47Z","timestamp":1575568967000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Investigating modifications to participant information materials to improve recruitment into a large randomized trial"],"prefix":"10.1186","volume":"20","author":[{"name":"The HPS2-THRIVE Collaborative Group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-0023","authenticated-orcid":false,"given":"Richard","family":"Haynes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wincott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rejive","family":"Dayanandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Parish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Landray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Armitage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"issue":"9253","key":"3779_CR1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0140-6736(00)03651-5","volume":"357","author":"R Collins","year":"2001","unstructured":"Collins R, MacMahon S. 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J Clin Epidemiol. 2012;65(2):147\u201354.","journal-title":"J Clin Epidemiol"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3779-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-019-3779-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3779-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:42:01Z","timestamp":1607042521000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-019-3779-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3779"],"URL":"https:\/\/doi.org\/10.1186\/s13063-019-3779-4","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"14 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The HPS2-THRIVE trial (and the studies described above) were reviewed and approved by the Berkshire Research Ethics Committee (reference 06\/MRE12\/043). As these trials involved different invitation processes, participants were not asked to provide consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"681"}}