Interval sample size reassessment
We defined length of treatment for the proposed trial as the average number of days of opioid treatment from the first weaning dose to cessation of opioid treatment. Due to a lack of available studies with published parameter estimates, we based the standard deviation used in the power calculations (6.9 to 8.0 days) on the number of days of opioid treatment for the The interval sample size reassessment will occur after 25% of the enrolled infants are medically ready for discharge, which will be 126 infants, assuming full enrollment of 502 infants. This coincides with the first Data Monitoring and Safety Committee (DSMC) safety review. The NRN DCC will re-estimate the sample size and provide the DSMC with this report. To re-estimate the sample size, we will use the pooled variance estimate calculated across both intervention groups from blinded data observed in 126 study participants. This blinded look at the interim data used for sample size refinement will not require any alpha adjustment in the final primary outcome analysis.