Data monitoring plan and stopping rules
EVENTS, RECRUITMENT, MEDICATION SIDE EFFECTS
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.There is wide variability in weaning opioid drug treatment across IDeA States and NRN hospitals. Well-characterized AEs and a DSMC will be critical to monitor the trial and to assure that the interventions are safe. The DSMC will assess safety after 25, 50, and 75% of the enrolled infants are medically ready for discharge, and it will assess efficacy and futility after 50% of the enrolled infants are medically ready for discharge. All interim analyses will utilize Bayesian modeling and predictive posterior inference based on neutral, enthusiastic, and skeptical priors. We will use Bayesian modeling for the interim analyses because the predictive posterior inference makes a clear statement about what to expect when we complete frequentist analysis on final data, given the interim results. The DSMC will receive an independent presentation of interim results, prepared by the study statistician. In preparation for the DSMC meeting, we will prepare a summary report of recruitment (by hospital), known outcome events, and any AEs (including medication side effects).