Hylke Salverda

62 Chapter 3 with the AVEA ventilator) being taken up at an early juncture in many preterm infants, precluding involvement in the study, and 2) fewer infants spending >18 of the preceding 24 hours with an FiO2 ≥ 0.25, in part attributable to the progressive approach to weaning FiO2 inherent in OxyGenie control. As a result, the recruitment rate was lower than expected. To prevent a loss of competence in handling the AVEA ventilator, potentially introducing a bias into the study, we decided to terminate the study prematurely. Truncated clinical studies can lead to over-exaggerated observed effects.29, 30 For our study, this would mean that the observed benefit for the OxyGenie controller in comparison to CLiO2 controller may over-estimate the true benefit. However, if we had planned for an interim analysis to decide for stopping the trial after 15 patients, we would have surpassed both the Pocock and O’Brien-Fleming boundary criteria for clearly showing evidence of benefit for the OxyGenie controller. For a single interim analysis Pocock recommends a p-threshold of 0.029431 and O’Brien-Fleming recommends a more conservative 0.0054 p-threshold32 to control for type I error due to repeated testing. The apparent benefit of OxyGenie is also demonstrated by a 11.7% improvement which is more than twice the clinically relevant difference of 5% for which the current study was powered. There was an imbalance between the two oxygen control devices in the proportion of missing values. Both algorithms use a built-in Masimo pulse oximeter with similar algorithms making it unlikely that the actual reliability of pulse oximeter measurement was different between ventilators. But, to ensure a prompt response to TR deviations, OxyGenie uses a 2-4 second averaging time whereas CLiO2 uses an 8 second averaging time. This could lead to more missing signal, as shorter averaging times are inherently more susceptible to disturbances. Furthermore, although the same SET technology is used, manufacturers are free to choose the signal quality threshold below which SpO2 is reported as missing. It seems likely that the handling of the SpO2 signal within the SLE6000 is more conservative in this respect. Because the proportion of missing signal was still relatively low in both oxygen control periods, its effect on the outcomes of this study is likely to have been modest. This study compared two ventilators rather than purely the AOC algorithms. It is possible that ventilator mechanics also played a role in the effectiveness of oxygen control, as well as other aspects of ventilator function including the circuit flow characteristics.33 However, this was a pragmatic choice as license agreements precluded us from implementing two algorithms in one ventilator. Contrary to our hypothesis, the benefit of an increase in SpO2 TR time with OxyGenie control was gained with a lesser occurrence of hyperoxaemia, at the cost of a minor