Cerebral oximetry monitoring versus usual care for extremely preterm infants: a detailed statistical analysis plan for the 2-year follow-up of the SafeBoosC-III randomised clinical trial

BackgroundThe SafeBoosC-III trial investigated treatment guided by cerebral oximetry monitoring for the first 72 hours after birth in extremely preterm infants and showed no effects on mortality or severe brain injury at 36 weeks postmenstrual age versus usual care. As severe brain injury in the neonatal period is not a strong predictor of long-term neurodevelopmental outcomes, the SafeBoosC-III follow-up study aims to assess the long-term benefits and harms of the experimental intervention versus usual care at two years of corrected age. This detailed statistical analysis plan outlines our approach for analysing outcomes in the SafeBoosC-III follow-up study. MethodsThe co-primary outcomes are 1) a composite of death or moderate-to-severe neurodevelopmental disability and 2) the mean Bayley-III/IV cognitive score. We will employ a 3-tier data model, incorporating routine clinical follow-up, parental questionnaires, and informal assessments to minimize missing data. All randomised participants with available data will be included in all analyses. Mixed-effect linear and logistic regression will be used to analyse the dichotomous and continuous co-primary outcomes, respectively. Sensitivity analyses will be conducted to address missing data and assess the robustness of our findings. DiscussionThe statistical analysis plan aims to ensure transparency and reduce the risk of outcome reporting bias. By including dichotomous and continuous co-primary outcomes, we aim to provide a comprehensive evaluation of the interventions effect on long-term benefits and harms.