eprintid: 10114668 rev_number: 17 eprint_status: archive userid: 608 dir: disk0/10/11/46/68 datestamp: 2020-11-12 14:36:49 lastmod: 2021-12-06 23:46:14 status_changed: 2020-11-12 14:36:49 type: article metadata_visibility: show creators_name: Orzechowska, I creators_name: Sadique, MZ creators_name: Thomas, K creators_name: Davis, P creators_name: Morris, KP creators_name: Mouncey, PR creators_name: Peters, MJ creators_name: Richards-Belle, A creators_name: Tume, LN creators_name: Ramnarayan, P creators_name: Harrison, DA title: First-line support for assistance in breathing in children: statistical and health economic analysis plan for the FIRST-ABC trial ispublished: pub subjects: GOSH divisions: UCL divisions: B02 divisions: C07 divisions: D05 divisions: D13 divisions: G24 keywords: Intensive care, Oxygen delivery, Paediatrics, Respiratory medicine, Statistics, epidemiology and research design note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. abstract: BACKGROUND: The FIRST-ABC trial comprises of two pragmatic, multicentre, parallel groups, non-inferiority randomised clinical trials designed to evaluate the clinical non-inferiority of first-line use of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP) in critically ill children who require non-invasive respiratory support (NRS). OBJECTIVES: To describe the pre-specified statistical and health economic analysis for the FIRST-ABC trial before completion of patient recruitment and data collection. METHODS: The statistical analysis plan was designed by the chief investigators and statisticians. We define the primary and secondary outcomes, summarise methods for data collection and safety monitoring, and present a detailed description of the planned statistical and health economic analysis. RESULTS: The primary clinical outcome is time to liberation from respiratory support. The primary effect estimate will be the adjusted hazard ratio, reported with a 95% confidence interval. As a sensitivity analysis, the primary analysis will be repeated using time to start weaning of NRS. Subgroup analyses will be performed to test for interactions between the effect of allocated treatment group and pre-specified baseline covariates. The health economic analysis will follow the intention-to-treat principle and report the mean (95% confidence interval) incremental costs, quality-adjusted life years (QALYs) and cost-effectiveness up to 6 months. All analyses will be performed separately for each of the two trials, and any results will not be combined. CONCLUSION: The FIRST-ABC trial will assess the non-inferiority of HFNC compared to CPAP in two parallel trials with shared infrastructure (step-up RCT and step-down RCT). We have developed a pre-specified statistical and health economics analysis plan for the FIRST-ABC study before trial completion to minimise analytical bias. TRIAL REGISTRATION: ISRCTN ISRCTN60048867 . Registered on 19 June 2019. date: 2020-10-31 date_type: published official_url: https://doi.org/10.1186/s13063-020-04818-w oa_status: green full_text_type: pub pmcid: PMC7602829 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1827622 doi: 10.1186/s13063-020-04818-w pii: 10.1186/s13063-020-04818-w lyricists_name: Peters, Mark lyricists_name: Ramnarayan, Padmanabhan lyricists_name: Richards-Belle, Alvin lyricists_id: MJPET74 lyricists_id: PRAMN86 lyricists_id: ARICA04 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Trials volume: 21 article_number: 903 event_location: England citation: Orzechowska, I; Sadique, MZ; Thomas, K; Davis, P; Morris, KP; Mouncey, PR; Peters, MJ; ... Harrison, DA; + view all <#> Orzechowska, I; Sadique, MZ; Thomas, K; Davis, P; Morris, KP; Mouncey, PR; Peters, MJ; Richards-Belle, A; Tume, LN; Ramnarayan, P; Harrison, DA; - view fewer <#> (2020) First-line support for assistance in breathing in children: statistical and health economic analysis plan for the FIRST-ABC trial. Trials , 21 , Article 903. 10.1186/s13063-020-04818-w <https://doi.org/10.1186/s13063-020-04818-w>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10114668/1/s13063-020-04818-w.pdf