Statistical analysis plan for the INHALEd nebulised unfractionated
HEParin for the treatment of hospitalised patients with COVID-19
(INHALE-HEP) meta-trial
Abstract
The INHALE-HEP meta-trial is a prospective collaborative individual
participant data meta-analysis of randomised controlled trials and early
phase studies, to evaluate whether inhaled nebulised UFH in hospitalised
patients with COVID-19 who do not require immediate invasive mechanical
ventilation, significantly reduces intubation (or death, for patients
who died before intubation) at day 28 compared to standard care alone.
Objective: In keeping with best practice and with the published
protocol, a pre-specified statistical analysis plan has been described
and made public before completion of patient recruitment and data
collection into the INHALE-HEP meta-trial. Methods: Our statistical
analysis plan was designed by the INHALE-HEP executive committee and
statisticians and approved by the INHALE-HEP steering committee. We
reviewed the data collected as specified in the meta-trial protocol and
collected in individual contributing studies. We present information
pertaining to data collection, pre-specified subgroups, and study
outcomes. Primary and secondary outcomes are defined, and additional
subgroup analyses of pre-defined variables are described. Results: We
have described our methods for presenting the trial profile and baseline
characteristics, as well as our Bayesian approach to monitoring and
meta-analysing individual patient data, outcomes and adverse events. All
analyses will follow the intention-to-treat principle, considering all
participants in the treatment group to which they were assigned, except
for cases lost to follow-up or withdrawn. Conclusion: To minimise
analytical bias, we have developed a statistical analysis plan and made
this available to the public domain before completion of patient
recruitment and data collection into the INHALE-HEP meta-trial.