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Non-invasive respiratory support in paediatric critical care: protocol for a cohort study emulating the FIRST-line
Elisa Giallongo1, Orlagh Carroll2, Padmanabhan Ramnarayan3
1ICNARC, London, UK elisa.giallongo@icnarc.org.
Insights
Target trial emulation (TTE) using routinely collected data can complement randomized controlled trials (RCTs). This study emulates the FIRST-ABC trial to compare high flow nasal cannula (HFNC) with continuous positive airway pressure (CPAP) in pediatric intensive care.
Area of Science:
- Pediatric Critical Care Medicine
- Epidemiology
- Health Services Research
Background:
- Target trial emulation (TTE) enhances non-randomized studies using routinely collected data.
- TTEs can complement randomized controlled trials (RCTs) by improving precision and external validity.
- The FIRST-ABC step-up RCT compared high flow nasal cannula (HFNC) with continuous positive airway pressure (CPAP) in pediatric critical care.
Purpose of the Study:
- To emulate the FIRST-ABC step-up RCT using the Target Trial Emulation (TTE) methodology.
- To compare the effectiveness of HFNC versus CPAP for respiratory support liberation in children using real-world data.
- To assess the feasibility and utility of TTE in pediatric critical care settings.
Main Methods:
- An observational study design using longitudinally collected data from the Paediatric Intensive Care Audit Network (PICANet) database.
- A new-user design emulating the eligibility criteria and outcomes of the FIRST-ABC RCT.
- Advanced quantitative doubly robust methods to minimize confounding, with subsequent Bayesian analysis for comparison.
Main Results:
- This section is a protocol and does not contain results yet.
- The study aims to benchmark results against the published FIRST-ABC trial.
- The analysis will provide insights into the effectiveness of HFNC versus CPAP.
Conclusions:
- This TTE protocol aims to validate the use of routinely collected data for emulating RCTs in pediatric critical care.
- The study will provide real-world evidence on respiratory support strategies, supplementing RCT findings.
- Findings will inform clinical practice and future research on leveraging observational data for evidence generation.
Introduction:
The development of the target trial emulation (TTE) methodology has enhanced the conduct of non-randomised studies. By leveraging readily available routinely collected data, TTEs offer opportunities for complementing randomised controlled trials (RCTs), providing more precise estimates and improving the external validity of RCTs. To explore this potential, we selected a successfully completed RCT as a case study. In the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up RCT, high flow nasal cannula (HFNC) was found to be non-inferior to continuous positive airway pressure (CPAP) in terms of time to liberation from respiratory support in the paediatric critical care setting. We will emulate the FIRST-ABC step-up trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database.
Methods And Analysis:
This is a protocol for a TTE that will use longitudinally collected data from the PICANet database. The study aims to emulate the FIRST-ABC step-up RCT using an observational study design in a frequentist framework. We will benchmark the results against the published trial. The study will apply a new-user design by selecting children admitted to paediatric intensive care units that started HFNC or non-invasive ventilatory support (as a surrogate for CPAP). The eligibility criteria and selected outcomes will reflect those of FIRST-ABC within the constraints of the available routinely collected data. We will use advanced quantitative doubly robust methods to minimise the impact of confounding by indication and allow for heterogeneity according to child characteristics. The analysis will be repeated using a Bayesian approach for follow-up research.
Ethics And Dissemination:
The research received ethics approval from the London School of Hygiene & Tropical Medicine Research Ethics Committee. This study will expand the findings from the FIRST-ABC step-up RCT, providing additional insight from a large representative sample using real-world data. The frequentist and Bayesian approaches will enable a discussion about the advantages and drawbacks of the two strategies. The results will be disseminated to the research and clinical community and made accessible to the public. In addition, the study results will be used in future research, which aims to supplement RCTs with additional evidence from a TTE.
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