Effect size and event rate estimation is necessary for sample size calculation in randomised clinical trials. Overestimation of the effect size and event rate can lead to inadequately powered studies and increased probability of false negative results. This is common in trials involving critically ill patients. However, such overestimation has not been systematically evaluated in trials involving neurocritical care. We aimed to conduct a systematic review of published randomised clinical trials involving critically ill neurological patients, to determine the accuracy of effect size and event rate estimation.

We will review randomised clinical trials involving adult critically ill neurological patients that were published from 2015 onwards in selected clinically useful and high-impact journals. We will include randomised clinical trials reporting a binary or time to event outcome, using two study groups, and a superiority design testing the efficacy of diagnostic, monitoring, therapeutic or process interventions. All eligible studies must report an estimated event rate in the control group and estimated effect size. All relevant studies will be identified through database searches. All study selection and data extraction will be conducted by two independent reviewers. We will use a random-effects model for pooling data. This review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Accuracy of effect size and event rate estimation will be evaluated by comparing the estimated and observed values. The association between the accuracy of the individual randomised clinical trial effect size and event rate estimation and rejection of the null hypothesis will be evaluated using logistic regression analysis. Multivariable linear regression analysis will be used to explore the factors associated with accuracy of effect size and event rate estimation. In addition, we will perform subgroup analysis by impact factor of the published journals, sample size of the studies and risk of bias.

As this systematic review will use data from previously published studies, it does not require ethics approval. Findings of this systematic review will be published in a peer-reviewed journal and will be presented at specialty-based conferences. The study will be included in the higher degree research thesis of the primary author.

CRD420251106394.

The management of severe traumatic brain injury (sTBI) in the intensive care unit (ICU) is focused on preventing secondary brain insults, by ensuring adequate cerebral perfusion, oxygenation and substrate delivery. Despite optimisation of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) using evidence-based guidelines, brain tissue hypoxia can still occur and is strongly associated with adverse functional outcomes post sTBI.

The Brain Oxygen Neuromonitoring in Australia and New Zealand Assessment – Global Trial (BONANZA-GT) is an international, two-arm, open-label, parallel group, randomised controlled trial comparing sTBI management incorporating early brain tissue oxygen (PbtO₂) monitoring and optimisation, with ICP/CPP-based management alone. A total of 860 adults admitted to participating institutions with non-penetrating sTBI and requiring insertion of an ICP monitor (as determined by the treating neurosurgeon) will be enrolled. The primary outcome is the proportion of patients with favourable neurological outcomes, as defined by a Glasgow Outcome Score-Extended (GOS-E) >4, at 6 months following injury. Key secondary outcomes include all-cause mortality at ICU discharge, hospital discharge, adverse events, as well as hospital and ICU length of stay and GOS-E at 12 months. The BONANZA-GT will determine whether a protocolised therapeutic strategy guided by continuous PbtO₂ monitoring in addition to ICP/CPP targets results in improved neurological outcomes when compared with standard care using ICP/CPP-guided management alone.

Approval has been obtained from relevant ethics boards in every jurisdiction that is participating in the trial. Inclusion of adults who lack capacity for informed consent will be governed in accordance with the legal requirements of each participating site. Study findings will be presented at scientific meetings and disseminated via peer-review publications.

Australian and New Zealand Clinical Trials Registry (ACTRN 12619001328167).