{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T17:51:50Z","timestamp":1776102710759,"version":"3.50.1"},"reference-count":51,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1176437"],"award-info":[{"award-number":["GNT1176437"]}],"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":"publisher","award":["GNT2016729"],"award-info":[{"award-number":["GNT2016729"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,3,12]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Induction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at \u226534 weeks\u2019 gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      This study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/circlenma.com\">https:\/\/circlenma.com<\/jats:ext-link>\n                      ). Patient and public involvement will guide the communication and interpretation of results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420251077464.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-110091","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:50:12Z","timestamp":1776099012000},"page":"e110091","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Methods of cervical ripening in induction of labour: an individual participant data network meta-analysis of randomised controlled trials (CIRCLE-NMA) study protocol"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9093-0147","authenticated-orcid":false,"given":"Nicole","family":"Au","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash Health, Monash University Faculty of Medicine, Nursing and Health Sciences, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-7092","authenticated-orcid":false,"given":"Malitha","family":"Patabendige","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash Health, Monash University Faculty of Medicine, Nursing and Health Sciences, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, St John of God Midland Public and Private Hospitals, Midland, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sol","family":"Libesman","sequence":"additional","affiliation":[{"name":"NextGen Evidence Synthesis Team, Evidence Integration, NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-8134","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"NextGen Evidence Synthesis Team, Evidence Integration, NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7052-1969","authenticated-orcid":false,"given":"Lyle C","family":"Gurrin","sequence":"additional","affiliation":[{"name":"University of Melbourne School of Population and Global Health, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":false,"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash Health, Monash University Faculty of Medicine, Nursing and Health Sciences, Clayton, Victoria, Australia"},{"name":"Monash University School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-0909","authenticated-orcid":false,"given":"Wentao","family":"Li","sequence":"additional","affiliation":[{"name":"National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health, University of New South Wales Faculty of Medicine, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"2026041309500715000_16.4.e110091.1","unstructured":"Australian institute of Health and Welfare . National maternity data development project: indications for induction of labour - research brief no.6. 2016. Available: https:\/\/pp.aihw.gov.au\/getmedia\/8c323db1-1ff9-4faf-8dc0-562d7f7a91b6\/brief_6_per-80.pdf.aspx"},{"key":"2026041309500715000_16.4.e110091.2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S1701-2163(15)30290-5","article-title":"Induction of labour: review","volume":"37","author":"Leduc","year":"2015","journal-title":"J Obstet Gynaecol Can"},{"key":"2026041309500715000_16.4.e110091.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.02065.x"},{"key":"2026041309500715000_16.4.e110091.4","unstructured":"National Institute for Health and Care Excellence . Inducing labour. NG207. London, UK NICE; 2021."},{"key":"2026041309500715000_16.4.e110091.5","doi-asserted-by":"crossref","unstructured":"Rattanakanokchai S , Gallos ID , Kietpeerakool C , et al . Methods of induction of labour: a network meta-analysis. Cochrane Database Syst Rev 2023;2023. doi:10.1002\/14651858.CD015234","DOI":"10.1002\/14651858.CD015234"},{"key":"2026041309500715000_16.4.e110091.6","doi-asserted-by":"crossref","first-page":"101515","DOI":"10.1016\/j.ajogmf.2024.101515","article-title":"How labor induction methods have evolved throughout history, from the Egyptian era to the present day: evolution, effectiveness, and safety","volume":"7","author":"Patabendige","year":"2025","journal-title":"Am J Obstet Gynecol MFM"},{"key":"2026041309500715000_16.4.e110091.7","doi-asserted-by":"crossref","first-page":"S696","DOI":"10.1016\/j.ajog.2022.01.005","article-title":"Single-balloon catheter with concomitant vaginal misoprostol is the most effective strategy for labor induction: a meta-review with network meta-analysis","volume":"230","author":"Sanchez-Ramos","year":"2024","journal-title":"Am J Obstet Gynecol"},{"key":"2026041309500715000_16.4.e110091.8","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1055\/a-2103-8329","article-title":"Synthetic Osmotic Dilators for Pre-Induction Cervical Ripening \u2013 an Evidence-Based Review","volume":"83","author":"Rath","year":"2023","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"2026041309500715000_16.4.e110091.9","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-016-1583-7"},{"key":"2026041309500715000_16.4.e110091.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjebm-2022-111931"},{"key":"2026041309500715000_16.4.e110091.11","doi-asserted-by":"publisher","DOI":"10.1111\/anae.15263"},{"key":"2026041309500715000_16.4.e110091.12","doi-asserted-by":"crossref","DOI":"10.1002\/cesm.12037","article-title":"Trustworthiness assessment as an inclusion criterion for systematic reviews-What is the impact on results?","volume":"1","author":"Weeks","year":"2023","journal-title":"Cochrane Evid Synth Methods"},{"key":"2026041309500715000_16.4.e110091.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-082068","article-title":"Investigating the impact of trial retractions on the healthcare evidence ecosystem (VITALITY Study I): retrospective cohort study","volume":"389","author":"Xu","year":"2025","journal-title":"BMJ"},{"key":"2026041309500715000_16.4.e110091.14","doi-asserted-by":"publisher","DOI":"10.3310\/hta20220"},{"key":"2026041309500715000_16.4.e110091.15","doi-asserted-by":"crossref","unstructured":"Anna Chaimani DMC , Li T , Higgins JP , et al . Chapter 11: undertaking network meta-analyses. In: Cochrane handbook for systematic reviews of interventions version 6.0. Cochrane, 2019.","DOI":"10.1002\/9781119536604.ch11"},{"key":"2026041309500715000_16.4.e110091.16","doi-asserted-by":"crossref","unstructured":"James Thomas LMA , Berlin JA , Elliott JH , et al . Chapter 22: prospective approaches to accumulating evidence. In: Cochrane handbook for systematic reviews of interventions. Version 6.0. Cochrane, 2019.","DOI":"10.1002\/9781119536604.ch22"},{"key":"2026041309500715000_16.4.e110091.17","unstructured":"Jayne F , Tierney LAS , Clarke M . Chapter 26: individual participant data. In: Cochrane handbook for systematic reviews of interventions. Version 6.0. Cochrane, 2013."},{"key":"2026041309500715000_16.4.e110091.18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3656"},{"key":"2026041309500715000_16.4.e110091.19","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026041309500715000_16.4.e110091.20","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/jrsm.1531","article-title":"Reporting of Cochrane systematic review protocols with network meta\u2010analyses\u2014A scoping review","volume":"13","author":"Wang","year":"2022","journal-title":"Res Synth Methods"},{"key":"2026041309500715000_16.4.e110091.21","doi-asserted-by":"publisher","DOI":"10.5662\/wjm.v11.i4.116"},{"key":"2026041309500715000_16.4.e110091.22","unstructured":"CIRCLE-NMA Collaborative . CIRCLE-NMA: cervical ripening for induction of labour collaborative evidence \u2013 network meta-analysis. 2025. Available: https:\/\/circlenma.com"},{"key":"2026041309500715000_16.4.e110091.23","unstructured":"World Health Organization . WHO recommendations on maternal and newborn care for a positive postnatal experience. Report No.: WHO\/MCA\/22.02. Geneva, Switzerland, 2022."},{"key":"2026041309500715000_16.4.e110091.24","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181b48ef5"},{"key":"2026041309500715000_16.4.e110091.25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/ijgo.15114","article-title":"FIGO good practice recommendations for induced or spontaneous labor at term: Prep-for-Labor triage to minimize risks and maximize favorable outcomes","volume":"163 Suppl 2","author":"Borovac-Pinheiro","year":"2023","journal-title":"Int J Gynaecol Obstet"},{"key":"2026041309500715000_16.4.e110091.26","article-title":"Mechanical methods for induction of labour","volume":"10","author":"de Vaan","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2026041309500715000_16.4.e110091.27","doi-asserted-by":"crossref","DOI":"10.1186\/s12874-020-01025-8","article-title":"Multivariate network meta-analysis incorporating class effects","volume":"20","author":"Owen","year":"2020","journal-title":"BMC Med Res Methodol"},{"key":"2026041309500715000_16.4.e110091.28","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1111\/1471-0528.15397","article-title":"Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study","volume":"125","author":"Dos Santos","year":"2018","journal-title":"BJOG"},{"key":"2026041309500715000_16.4.e110091.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.01.021"},{"key":"2026041309500715000_16.4.e110091.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01845-1"},{"key":"2026041309500715000_16.4.e110091.31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/uog.23563","article-title":"Foley catheter vs oral misoprostol for induction of labor: individual participant data meta-analysis","volume":"57","author":"Kemper","year":"2021","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2026041309500715000_16.4.e110091.32","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/aogs.14626","article-title":"Double-vs single-balloon catheter for induction of labor: Systematic review and individual participant data meta-analysis","volume":"102","author":"Peel","year":"2023","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2026041309500715000_16.4.e110091.33","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/1471-0528.17794","article-title":"Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials","volume":"131","author":"Patabendige","year":"2024","journal-title":"BJOG"},{"key":"2026041309500715000_16.4.e110091.34","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/aogs.15092","article-title":"Inpatient vaginal dinoprostone vs outpatient balloon catheters for cervical ripening in induction of labor: An individual participant data meta-analysis of randomized controlled trials","volume":"104","author":"Chan","year":"2025","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2026041309500715000_16.4.e110091.35","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1111\/1471-0528.18253","article-title":"Outpatient or Inpatient Setting for Cervical Ripening Before Induction of Labour: An Individual Participant Data Meta-Analysis","volume":"132","author":"Patabendige","year":"2025","journal-title":"BJOG"},{"key":"2026041309500715000_16.4.e110091.36","doi-asserted-by":"crossref","DOI":"10.1186\/s41073-023-00130-8","article-title":"Checklist to assess Trustworthiness in RAndomised Controlled Trials (TRACT checklist): concept proposal and pilot","volume":"8","author":"Mol","year":"2023","journal-title":"Res Integr Peer Rev"},{"key":"2026041309500715000_16.4.e110091.37","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2025.103346","article-title":"Data-sharing and trustworthiness of trials evaluating cervical ripening in induction of labour: a meta-epidemiological study of randomised controlled trials","volume":"85","author":"Patabendige","year":"2025","journal-title":"EClinicalMedicine"},{"key":"2026041309500715000_16.4.e110091.38","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/jrsm.1738","article-title":"The Individual Participant Data Integrity Tool for assessing the integrity of randomised trials","volume":"15","author":"Hunter","year":"2024","journal-title":"Res Synth Methods"},{"key":"2026041309500715000_16.4.e110091.39","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"},{"key":"2026041309500715000_16.4.e110091.40","doi-asserted-by":"crossref","first-page":"111875","DOI":"10.1016\/j.jclinepi.2025.111875","article-title":"Individual participant data informed risk of bias assessments for randomized controlled trials in systematic reviews and meta-analyses","volume":"185","author":"Sotiropoulos","year":"2025","journal-title":"J Clin Epidemiol"},{"key":"2026041309500715000_16.4.e110091.41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003082","article-title":"CINeMA: An approach for assessing confidence in the results of a network meta-analysis","volume":"17","author":"Nikolakopoulou","year":"2020","journal-title":"PLoS Med"},{"key":"2026041309500715000_16.4.e110091.42","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7141"},{"key":"2026041309500715000_16.4.e110091.43","doi-asserted-by":"crossref","unstructured":"Riley RDT , Jayne F , Stewart LA . Individual participant data meta-analysis: a handbook for healthcare research. Wiley-Blackwell, 2021.","DOI":"10.1002\/9781119333784"},{"key":"2026041309500715000_16.4.e110091.44","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/jrsm.1037","article-title":"Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool","volume":"3","author":"Salanti","year":"2012","journal-title":"Res Synth Methods"},{"key":"2026041309500715000_16.4.e110091.45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/jrsm.1044","article-title":"Consistency and inconsistency in network meta\u2010analysis: concepts and models for multi\u2010arm studies","volume":"3","author":"Higgins","year":"2012","journal-title":"Res Synth Methods"},{"key":"2026041309500715000_16.4.e110091.46","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3767"},{"key":"2026041309500715000_16.4.e110091.47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076654","article-title":"Graphical tools for network meta-analysis in STATA","volume":"8","author":"Chaimani","year":"2013","journal-title":"PLoS One"},{"key":"2026041309500715000_16.4.e110091.48","unstructured":"R Core Team . R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2022."},{"key":"2026041309500715000_16.4.e110091.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.03.016"},{"key":"2026041309500715000_16.4.e110091.50","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2020-037744","article-title":"Agreement between ranking metrics in network meta-analysis: an empirical study","volume":"10","author":"Chiocchia","year":"2020","journal-title":"BMJ Open"},{"key":"2026041309500715000_16.4.e110091.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.02.016"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-110091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:50:19Z","timestamp":1776099019000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-110091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1136\/bmjopen-2025-110091"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-110091","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]}}}