{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:10:40Z","timestamp":1777543840413,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00004_09 and MC_UU_123023_29"],"award-info":[{"award-number":["MC_UU_00004_09 and MC_UU_123023_29"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","award":["UNDP-UNFPA-UNICEF-WHO"],"award-info":[{"award-number":["UNDP-UNFPA-UNICEF-WHO"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms at interim stages even if they are all showing some promise against the control arm. This will put a limit on the maximum number of patients required and reduce the associated costs. Motivated by the World Health Organization Refractory HaEmorrhage Devices trial in postpartum haemorrhage, we explored the properties of such a selection design in a randomised phase III setting and compared it with other alternatives. The objectives are: (1) to investigate how the timing of treatment selection affects the operating characteristics; (2) to explore the use of an information-rich (continuous) intermediate outcome to select the best-performing arm, out of four treatment arms, compared with using the primary (binary) outcome for selection at the interim stage; and (3) to identify factors that can affect the efficiency of the design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We conducted simulations based on the refractory haemorrhage devices multi-arm multi-stage selection trial to investigate the impact of the timing of treatment selection and applying an adaptive allocation ratio on the probability of correct selection, overall power and familywise type I error rate. Simulations were also conducted to explore how other design parameters will affect both the maximum sample size and trial timelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The results indicate that the overall power of the trial is bounded by the probability of \u2018correct\u2019 selection at the selection stage. The results showed that good operating characteristics are achieved if the treatment selection is conducted at around 17% of information time. Our results also showed that although randomising more patients to research arms before selection will increase the probability of selecting correctly, this will not increase the overall efficiency of the (selection) design compared with the fixed allocation ratio of 1:1 to all arms throughout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Multi-arm multi-stage selection designs are efficient and flexible with desirable operating characteristics. We give guidance on many aspects of these designs including selecting the intermediate outcome measure, the timing of treatment selection, and choosing the operating characteristics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745221136527","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T06:24:29Z","timestamp":1673936669000},"page":"71-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Treatment selection in multi-arm multi-stage designs: With application to a postpartum haemorrhage trial"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-5899","authenticated-orcid":false,"given":"Babak","family":"Choodari-Oskooei","sequence":"first","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London (UCL), London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soe Soe","family":"Thwin","sequence":"additional","affiliation":[{"name":"Maternal and Perinatal Health Unit, Department of Sexual and Reproductive Health and Research (SRH), World Health Organization (WHO), Geneve, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-8671","authenticated-orcid":false,"given":"Alexandra","family":"Blenkinsop","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London (UCL), London, UK"},{"name":"Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Widmer","sequence":"additional","affiliation":[{"name":"Maternal and Perinatal Health Unit, Department of Sexual and Reproductive Health and Research (SRH), World Health Organization (WHO), Geneve, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Althabe","sequence":"additional","affiliation":[{"name":"Maternal and Perinatal Health Unit, Department of Sexual and Reproductive Health and Research (SRH), World Health Organization (WHO), Geneve, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh KB","family":"Parmar","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London (UCL), London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"bibr1-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1430"},{"key":"bibr2-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-12-81"},{"key":"bibr3-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1177\/1740774518823551"},{"key":"bibr4-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-52636-2_110"},{"key":"bibr5-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1002\/pst.501"},{"key":"bibr6-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijoa.2021.102982"},{"key":"bibr7-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16040"},{"key":"bibr8-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1177\/1740774520904346"},{"key":"bibr9-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0325"},{"key":"bibr10-17407745221136527","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(00)00106-9"},{"key":"bibr11-17407745221136527","volume-title":"Stata 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