{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T21:21:53Z","timestamp":1777929713321,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T00:00:00Z","timestamp":1496793600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stat Methods Med Res"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Just over half of publicly funded trials recruit their target sample size within the planned study duration. When recruitment targets are missed, the funder of a trial is faced with the decision of either committing further resources to the study or risk that a worthwhile treatment effect may be missed by an underpowered final analysis. To avoid this challenging situation, when there is insufficient prior evidence to support predicted recruitment rates, funders now require feasibility assessments to be performed in the early stages of trials. Progression criteria are usually specified and agreed with the funder ahead of time. To date, however, the progression rules used are typically ad hoc. In addition, rules routinely permit adaptations to recruitment strategies but do not stipulate criteria for evaluating their effectiveness. In this paper, we develop a framework for planning and designing internal pilot studies which permit a trial to be stopped early if recruitment is disappointing or to continue to full recruitment if enrolment during the feasibility phase is adequate. This framework enables a progression rule to be pre-specified and agreed upon prior to starting a trial. The novel two-stage designs stipulate that if neither of these situations arises, adaptations to recruitment should be made and subsequently evaluated to establish whether they have been successful. We derive optimal progression rules for internal pilot studies which minimise the expected trial overrun and maintain a high probability of completing the study when the recruitment rate is adequate. The advantages of this procedure are illustrated using a real trial example.<\/jats:p>","DOI":"10.1177\/0962280217708906","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T05:44:54Z","timestamp":1496814294000},"page":"3612-3627","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["A framework for prospectively defining progression rules for internal pilot studies monitoring recruitment"],"prefix":"10.1177","volume":"27","author":[{"given":"Lisa V","family":"Hampson","sequence":"first","affiliation":[{"name":"Department of Mathematics and Statistics, Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster, UK"},{"name":"Statistical Innovation, Advanced Analytics Centre, AstraZeneca, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula R","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, MRC North-West Hub for Trials Methodology Research, University of Liverpool, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J","family":"Wilby","sequence":"additional","affiliation":[{"name":"Walton Centre NHS Foundation Trust, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Jaki","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,6,7]]},"reference":[{"key":"bibr1-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmm051"},{"key":"bibr2-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-14-166"},{"key":"bibr3-0962280217708906","doi-asserted-by":"publisher","DOI":"10.3310\/hta11480"},{"key":"bibr4-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(01)00353-5"},{"key":"bibr5-0962280217708906","unstructured":"National Institute for Health Research. Recruitment rate progression rules for internal pilot studies for HTA trials, http:\/\/www.themedcalls.nihr.ac.uk_data\/assets\/pdf_file\/0003\/75198\/Progression-rules-for-internal-pilot-studies.pdf (accessed 3 March 2014)."},{"key":"bibr6-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19991230)18:24<3481::AID-SIM301>3.0.CO;2-C"},{"key":"bibr7-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19991230)18:24<3493::AID-SIM302>3.0.CO;2-2"},{"key":"bibr8-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(83)90170-4"},{"key":"bibr9-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3128"},{"key":"bibr10-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6359"},{"key":"bibr11-0962280217708906","unstructured":"National Institute for Health Research. HTA \u2013 12\/201\/10: Multi-centre randomised control trial comparing the clinical and cost effectiveness of trans-foraminal epidural steroid injection to surgical microdiscectomy for the treatment of chronic radicular pain secondary to prolapsed intervertebral disc herniation. Trial protocol Version 2.0 Dated 30\/09\/2014, http:\/\/www.nets.nihr.ac.uk\/projects\/hta\/1220110 (accessed 29 October 2014)."},{"key":"bibr12-0962280217708906","volume-title":"The design and analysis of sequential clinical trials (revised 2nd edition)","author":"Whitehead J","year":"1997"},{"key":"bibr13-0962280217708906","doi-asserted-by":"crossref","unstructured":"Treweek S, Mitchell E, Pitkethly M, et\u00a0al. Strategies to improve recruitment to randomised controlled trials.\n                      Cochrane Database Syst Rev\n                      2010. 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HTA \u2013 13\/04\/46: a randomised comparison of femtosecond laser assisted vs manual phacoemulsification cataract surgery for adults with visually significant cataract: the FACT trial, http:\/\/www.nets.nihr.ac.uk\/projects\/hta\/130446 (accessed 4 February 2017)."},{"key":"bibr17-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-10-63"},{"key":"bibr18-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1177\/1740774512447996"},{"key":"bibr19-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2015.07.010"},{"key":"bibr20-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980815\/30)17:15\/16<1753::AID-SIM977>3.0.CO;2-X"},{"key":"bibr21-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1506"},{"key":"bibr22-0962280217708906","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/sim.3847","volume":"29","author":"Zhang X","year":"2010","journal-title":"Stat Med"},{"key":"bibr23-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2956"},{"key":"bibr24-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1080\/03610926.2011.581189"},{"key":"bibr25-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4495"},{"key":"bibr26-0962280217708906","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5979"},{"key":"bibr27-0962280217708906","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2013"},{"key":"bibr28-0962280217708906","unstructured":"Johnson SG and Narasimhan B.\n                      cubature: adaptive multivariate integration over hypercubes\n                      , 2013, http:\/\/CRAN.R-project.org\/package=cubature. 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