Abstract
Background:
The INHALE d nebulised unfractionated HEP arin for the
treatment of hospitalised patients with COVID-19 (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they were assigned, except for cases lost to follow-up or withdrawn.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.