TY - JOUR
T1 - First-line support for assistance in breathing in children
T2 - statistical and health economic analysis plan for the FIRST-ABC trial
AU - Orzechowska, Izabella
AU - Sadique, M. Zia
AU - Thomas, Karen
AU - Davis, Peter
AU - Morris, Kevin P.
AU - Mouncey, Paul R.
AU - Peters, Mark J.
AU - Richards-Belle, Alvin
AU - Tume, Lyvonne N.
AU - Ramnarayan, Padmanabhan
AU - Harrison, David A.
N1 - Funding Information:
The authors thank the co-investigators (Julie Lester, Kathy Rowan, Richard Feltbower and Richard Grieve) and members of the trial team (Michelle Saull and Laura Drikite) for their contribution to the design and/or set-up and delivery of FIRST-ABC. The authors also thank the research and clinical staff at the UK participating sites: Addenbrookes’ Hospital (Cambridge), Alder Hey Children’s Hospital (Liverpool), Birmingham Women and Children’s Hospital, Bristol Royal Hospital for Children, Chelsea and Westminster Hospital, Evelina London Children’s Hospital, Great North Children’s Hospital (Newcastle), Great Ormond Street Hospital (London), Hull Royal Infirmary, James Cook University Hospital (Middlesbrough), John Radcliffe Hospital (Oxford), King’s College Hospital (London), Leicester Royal Infirmary and Glenfield Hospital, Noah’s Ark Children’s Hospital for Wales (Cardiff), Queens Medical Centre (Nottingham), Royal Alexandra Children’s Hospital (Brighton), Royal Brompton Hospital (London), Royal Hospital for Sick Children Edinburgh, Royal Manchester Children’s Hospital, Sheffield Children’s Hospital, Southampton Children’s Hospital, St George’s Hospital (London), St Mary’s Hospital (London) and The Royal London Hospital. The authors acknowledge the UK Paediatric Intensive Care Society – Study Group for supporting the trial.
Funding Information:
This trial is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number: 17/94/28). Great Ormond Street Hospital for Children NHS Foundation Trust is the trial sponsor. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care nor the Sponsor. The funder and sponsor had no role in the writing of this article or the decision to submit the SAP for publication. Acknowledgements
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - Intensive care
KW - Oxygen delivery
KW - Paediatrics
KW - Respiratory medicine
KW - Statistics, epidemiology and research design
UR - http://www.scopus.com/inward/record.url?scp=85094653717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094653717&partnerID=8YFLogxK
U2 - 10.1186/s13063-020-04818-w
DO - 10.1186/s13063-020-04818-w
M3 - Article (journal)
C2 - 33129360
AN - SCOPUS:85094653717
SN - 1745-6215
VL - 21
JO - Trials
JF - Trials
IS - 1
M1 - 903
ER -