{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:59:43Z","timestamp":1777417183049,"version":"3.51.4"},"reference-count":17,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1103262"],"award-info":[{"award-number":["1103262"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["1104975"],"award-info":[{"award-number":["1104975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["1158696"],"award-info":[{"award-number":["1158696"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background<\/ns3:bold>\n                    : The Benefits and Risks of Iron interventionS in Children (BRISC) trial will evaluate the impact of universal supplementation with iron supplements or iron-containing multiple micronutrient powders (MNPs) compared with placebo given for 3 months on child development, growth, morbidity, laboratory indices of anaemia, iron deficiency, and inflammation at end of intervention and after a further 9 months post intervention in children aged 8 months living in rural Bangladesh. This paper describes the statistical analysis plan.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods<\/ns3:bold>\n                    : BRISC is a multi-site, three-arm, double-dummy blinded, parallel group, randomised control superiority trial in 3300 children. The statistical analysis plan was developed by the trial statistician in consultation with the trial steering committee and trial management committee based on the protocol, data collection forms, and study outcomes available in the blinded study database.\u00a0\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusion<\/ns3:bold>\n                    : This detailed statistical analysis plan published prior to unblinding the allocated treatments will support the statistical analyses and reporting of the BRISC trial to be undertaken after unblinding. It allows for transparency as well as reproducibility of statistical analyses and reporting.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Registration:<\/ns3:bold>\n                    Australian New Zealand Clinical Trials Registry ACTRN12617000660381 (registered on 8 May 2017); World Health Organization Universal Trial Number U1111-1196-1125.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.23383.1","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T11:10:09Z","timestamp":1590145809000},"page":"427","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Benefits and Risks of Iron interventionS in Children (BRISC) trial: Statistical analysis plan"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1997-3999","authenticated-orcid":false,"given":"Sabine","family":"Braat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Larson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Imrul","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jena Derakhshani","family":"Hamadani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheikh Jamal","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamima","family":"Shiraji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Saiful Alam","family":"Bhuiyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverley-Ann","family":"Biggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sant-Rayn","family":"Pasricha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"ref-1","article-title":"Guideline: daily iron supplementation in infants and children.","year":"2016"},{"key":"ref-2","article-title":"WHO guideline: Use of multiple micronutrient powders for point-of-use fortication of foods consumed by infants and young children aged 6\u2013 23 months and children aged 2\u2013 12 years.","year":"2016"},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"e77-e86","DOI":"10.1016\/S2214-109X(13)70046-9","article-title":"Effect of daily iron supplementation on health in children aged 4\u2014 23 months: a systematic review and meta-analysis of randomised controlled trials.","volume":"1","author":"S Pasricha","year":"2013","journal-title":"Lancet Glob Health."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"25-38","DOI":"10.1159\/000480742","article-title":"Iron and Cognitive Development: What Is the Evidence?","volume":"71","author":"L Larson","year":"2017","journal-title":"Ann Nutr Metab."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"29-40","DOI":"10.1016\/S0140-6736(13)60437-7","article-title":"Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial.","volume":"382","author":"S Soofi","year":"2013","journal-title":"Lancet."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"e018325","DOI":"10.1136\/bmjopen-2017-018325","article-title":"Benefits and risks of Iron interventions in children (BRISC): protocol for a three-arm parallel-group randomised controlled field trial in Bangladesh.","volume":"7","author":"M Hasan","year":"2017","journal-title":"BMJ open."},{"key":"ref-7","article-title":"Bayley Scales of Infant Development Manual.","author":"N Bayley","year":"2006"},{"key":"ref-8","article-title":"WHO child growth standards: length\/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development","year":"2006"},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"237-54","DOI":"10.1093\/jpepsy\/15.2.237","article-title":"Behavioral style in failure-to-thrive infants: a preliminary communication.","volume":"15","author":"D Wolke","year":"1990","journal-title":"J Pediatr Psychol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1765-71","DOI":"10.3945\/jn.109.106294","article-title":"Undernourished children have different temperaments than better-nourished children in rural Bangladesh.","volume":"139","author":"H Baker-Henningham","year":"2009","journal-title":"J Nutr."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"561-66","DOI":"10.1016\/S0140-6736(03)12515-9","article-title":"Inequities among the very poor: health care for children in rural southern Tanzania.","volume":"361","author":"J Schellenberg","year":"2003","journal-title":"Lancet."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"385-401","DOI":"10.1177\/014662167700100306","article-title":"The CES-D scale a self-report depression scale for research in the general population.","volume":"1","author":"L Radloff","year":"1977","journal-title":"Applied psychological measurement."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"169-76","DOI":"10.1007\/s001270200011","article-title":"Maternal depression in three Latin American samples.","volume":"37","author":"A Wolf","year":"2002","journal-title":"Soc Psychiatry Psychiatr Epidemiol."},{"key":"ref-14","doi-asserted-by":"crossref","DOI":"10.1037\/e576842013-001","article-title":"Household Food Insecurity Access Scale (HFIAS) for measurement of food access: indicator guide: version 3","author":"J Coates","year":"2007"},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"23-33","DOI":"10.3329\/jhpn.v28i1.4520","article-title":"Use of family care indicators and their relationship with child development in Bangladesh.","volume":"28","author":"J Hamadani","year":"2010","journal-title":"J Health Popul Nutr."},{"key":"ref-16","first-page":"134-48","article-title":"Longitudinal data analysis of continuous and discrete responses for pre-post designs.","volume":"62","author":"K Liang","year":"2000","journal-title":"Sankhy\u0101: The Indian Journal of Statistics, Series B."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"327-47","DOI":"10.1191\/0962280205sm406oa","article-title":"Uses and limitations of randomization-based efficacy estimators.","volume":"14","author":"I White","year":"2005","journal-title":"Stat Methods Med Res."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/9-427\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-427\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-427\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T07:39:44Z","timestamp":1649144384000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/9-427\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,22]]},"references-count":17,"URL":"https:\/\/doi.org\/10.12688\/f1000research.23383.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.25810.r119673","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.25810.r65657","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.25810.r65657","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.25810.r119673","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,22]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/9-427\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.25810.r65657, Deborah Ridout, Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, UK, 10 Jul 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-427\/v1#referee-response-65657","order":0,"name":"referee-response-65657","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sabine Braat<\/b>; \n<i>Posted: 01 Sep 2020<\/i>; Thank you for the opportunity to respond to the comments of reviewer #1. We appreciate the review provided and have addressed each point below.  \n<i>This is a well-designed, large randomised trial investigating the use of iron supplementation or home fortification with multiple micronutrient powders, on cognitive development outcome in 8-month old children. The study is set in Bangaldesh and will be conducted over 3 sites. 3,300 children will be recruited and randomised to one of 3 arms, one of which is a placebo. The study is blinded, so that both family and assessor is unaware of group allocation. The study is designed to assess superiority. Secondary outcomes will assess motor and language ability on the Bayley scale as well as prevalence of anaemia and iron deficiency, growth, and infection risks.<\/i>  Response: We thank the reviewer for the feedback.  \n<i>1. The investigators plan to stratify the randomisation by union and sex, which seems sensible and I wonder if they should also consider weight for age as a stratifying factor.<\/i>  Response: We thank the reviewer for this suggestion. The trial is no longer recruiting and finished in 2020. In the \u201cSensitivity analyses\u201d section we have pre-specified an analysis model that may adjust for characteristics that are unbalanced between treatment arms. This may include weight if it is unbalanced. &nbsp; \n<i>2. An area that may need clarification is around the superiority aspect of the trial, this is mentioned several times, although it is not clear whether the power calculation and planned analyses are considering this design feature.<\/i>  Response: We thank the reviewer for the comment. In the \u201cAims\u201d section we refer to the study as a superiority study with the primary objective \u201c...to determine whether 3 months of iron supplementation or home fortification with MNPs is superior to placebo on cognitive development ...\u201d &nbsp;Both the sample size and the analyses of cognitive development are based on a superiority hypothesis.  \n<i>3. There is a possibility that a comparison will be made between the 2 treatments groups, groups 1 &amp; 2, and the plan for this is described well. It is not so clear how these results will be interpreted, is the same effect size of 2 units on the Cognitive Bayley scale appropriate here?<\/i>  Response: We thank the reviewer for this question. The sample size calculation assumed the same effect size for both active treatment groups versus placebo, with 2 units representing a clinically meaningful effect size. The two primary comparisons consist of each active dose vs placebo. When interpreting the results for both active doses, we will take into consideration the findings of the primary outcome (cognitive Bayley scale), secondary outcomes, and safety outcomes.","URL":"https:\/\/f1000research.com\/articles\/9-427\/v1#referee-comment-5881","order":1,"name":"referee-comment-5881","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.25810.r119673, Sonia Lewycka, Hanoi Unit, Oxford University Clinical Research Unit, Hanoi, Vietnam, 05 Apr 2022, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-427\/v1#referee-response-119673","order":2,"name":"referee-response-119673","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The research study was funded by the National Health and Medical Research Council (NHMRC) grant number 1103262. Sant-Rayn Pasricha is funded by an Australian NHMRC Career Development Fellowship ID 1158696. Julie A Simpson is funded by an Australian NHMRC Senior Research Fellowship ID 1104975. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}