{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T22:23:28Z","timestamp":1788647008400,"version":"build-2803163510"},"reference-count":13,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000848","name":"University of Edinburgh","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000848","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,8,9]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial. Methods to estimate the margin are heterogeneous but generally based on clinical judgement and statistical reasoning, and hence tailored to each clinical situation. Yet an appraisal of NI in clinical trials has not been undertaken. Therefore the aim of this systematic review is to assess the reporting and methodological quality of defining the NI margin. Surgical NI trials have been chosen as our prototype to assess this.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We will conduct a systematic review of published randomised controlled trials in abdominal surgery that use an NI design. Key eligibility criteria will be: surgical intervention in at least one trial arm; adult patients and a sample size of 100 or more. Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception until the date of the search. Identified studies will be assessed for reporting according to the CONSORT recommendations. The outcomes are the description of the methods for defining the NI margin, and the robustness of the NI margin estimation. The latter will be based on simulations using alternative assumptions for model parameters. The results of the simulation will be compared with the trial authors\u2019 conclusions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Anticipated results<\/jats:title>\n                    <jats:p>The review will describe and appraise the design and reporting of surgical NI trials including shortcomings thereof and allow a comparison with pharmaceutical trials. These findings will inform researchers on the appropriate design and pitfalls when conducting surgical randomised controlled trials with an NI design and promote thorough and standardised reporting of study findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval is not required and any changes to the protocol will be communicated via the registration platform. The final manuscript will be submitted to a journal for publication and the findings will be disseminated through conference presentations to inform researchers and the public.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-089587","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T04:48:45Z","timestamp":1724474925000},"page":"e089587","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Defining non-inferiority margins in randomised controlled surgical trials: a protocol for a systematic review"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7109-3545","authenticated-orcid":false,"given":"Christoph","family":"Kuemmerli","sequence":"first","affiliation":[{"name":"Molecular, Genetic and Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK"},{"name":"Department of Surgery, University Digestive Health Care Center, Clarunis, University Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain J","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Centre for Biomedicine & Global Health, Edinburgh Napier University, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Skipworth","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Laird","sequence":"additional","affiliation":[{"name":"European Palliative Care Research Centre, Edinburgh Cancer Research Centre, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,8,24]]},"reference":[{"key":"2025121512040884000_14.8.e089587.1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013550","article-title":"Room for improvement in conducting and reporting non-inferiority randomized controlled trials on drugs: a systematic review","volume":"5","author":"Wangge","year":"2010","journal-title":"PLoS One"},{"key":"2025121512040884000_14.8.e089587.2","doi-asserted-by":"crossref","DOI":"10.1186\/1745-6215-13-214","article-title":"Quality of reporting of clinical non-inferiority and equivalence randomised trials--update and extension","volume":"13","author":"Schiller","year":"2012","journal-title":"Trials"},{"key":"2025121512040884000_14.8.e089587.3","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-012594","article-title":"Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals","volume":"6","author":"Rehal","year":"2016","journal-title":"BMJ Open"},{"key":"2025121512040884000_14.8.e089587.4","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-017-1859-x","article-title":"Methods of defining the non-inferiority margin in randomized, double-blind controlled trials: a systematic review","volume":"18","author":"Althunian","year":"2017","journal-title":"Trials"},{"key":"2025121512040884000_14.8.e089587.5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.10.1152"},{"key":"2025121512040884000_14.8.e089587.6","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1093\/cid\/ciad308","article-title":"Methodological and reporting quality of noninferiority randomized controlled trials comparing antiretroviral therapies: a systematic review","volume":"77","author":"Lo","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2025121512040884000_14.8.e089587.7","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2018-314874"},{"key":"2025121512040884000_14.8.e089587.8","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-021-05686-8","article-title":"Confidence interval of risk difference by different statistical methods and its impact on the study conclusion in antibiotic non-inferiority trials","volume":"22","author":"Bai","year":"2021","journal-title":"Trials"},{"key":"2025121512040884000_14.8.e089587.9","doi-asserted-by":"publisher","DOI":"10.2307\/2685779"},{"key":"2025121512040884000_14.8.e089587.10","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780040211"},{"key":"2025121512040884000_14.8.e089587.11","doi-asserted-by":"crossref","unstructured":"Newcombe RG . Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med 1998;873\u201390. doi:10.1002\/(sici)1097-0258(19980430)17:83.0.co;2-i","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<873::AID-SIM779>3.0.CO;2-I"},{"key":"2025121512040884000_14.8.e089587.12","doi-asserted-by":"publisher","DOI":"10.2307\/2276774"},{"key":"2025121512040884000_14.8.e089587.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-089587","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T20:04:13Z","timestamp":1765829053000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-089587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":13,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,24]]},"published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1136\/bmjopen-2024-089587"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-089587","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]}}}