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

Background: The SafeBoosC-III trial investigated treatment guided by cerebral oximetry monitoring for the first 72 h after birth in extremely preterm infants (born below 28 weeks gestational age) 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 prospectively planned SafeBoosC-III follow-up study aims to assess the long-term benefits and harms of the experimental intervention versus usual care at 2 years of corrected age. The statistical analysis plan presented here was defined before data collection was complete and outlines our approach for analysing outcomes in the SafeBoosC-III follow-up study. Methods: The co-primary outcomes were (1) a composite of death or moderate-to-severe neurodevelopmental disability and (2) the mean Bayley-III/IV cognitive score. We employed a 3-tier data model, incorporating routine clinical follow-up, parental questionnaires, and informal assessments to minimise missing data. All randomised participants with available data were included in all analyses. Mixed-effect linear and logistic regression was used to analyse the dichotomous and continuous co-primary outcomes, respectively. Sensitivity analyses were conducted to address missing data and assess the robustness of our findings. Discussion: This statistical analysis plan aimed to ensure transparency and reduce the risk of outcome reporting bias. By including dichotomous and continuous co-primary outcomes, we aimed to provide a comprehensive evaluation of the intervention's effect on long-term benefits and harms. Trial registration: ClinicalTrials.gov NCT05134116. Registered on November 24, 2021.