The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants

Table 4 Stopping rules based on the O’Brien-Fleming alpha spending method

Interim	Decision action	Z test statistic boundary value^a	P value
First	§ Stop the trial due to higher incidence of composite adverse events in EA	Z > 3.66474	P < 0.00025
	§ Stop the trial due to higher incidence of composite adverse events in placebo	Z < −3.66474	P < 0.00025
	§ Continue the trial	Z in [−3.66474, 3.66474]	P³ 0.00025
Second	§ Stop the trial due to higher incidence of composite adverse events in EA	Z > 2.50210	P < 0.01235
	§ Stop the trial due to higher incidence of composite adverse events in placebo	Z < −2.50210	P < 0.01235
	§ Continue the trial	Z in [−2.50210, 2.50210]	P³ 0.01235
Final	§ Incidence of composite adverse events is significantly higher in EA	Z > 1.96	P < 0.05
	§ Incidence of composite adverse events is significantly higher in placebo	Z < −1.96	P < 0.05
	§ Incidence of composite adverse events is not significantly different between EA and placebo	Z in [−1.96, 1.96]	P³ 0.05

^aZ test statistic = [(incidence of NEC/LOS/death in EA) − (incidence of NEC/LOS/death in placebo)]/SE

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