Interim safety analysis
seizure
REGRESSION
In addition to monitoring AEs and SAEs, the DSMC will use Bayesian analyses to monitor seizure occurrence. The DSMC will assess seizure occurrence at three interim reviews, 25, 50, and 75% of enrollment. Within the slow-wean intervention, we expect the seizure proportion to be 0.03, and within the rapid-wean intervention, we expect this proportion to be higher. Based on clinical experience, the study team offers the following guideline for stopping the trial early for safety. Yet as with Efficacy and Futility, per the DSMC charter, all protocol suggested stopping guidelines are advisory and the DSMC can choose to ignore them. If the seizure proportion is 0.03 in the slow-wean intervention, and the seizure proportion is greater than 0.10 in the rapid-wean intervention, then the DSMC may consider stopping the trial for safety. As such, the interim analyses of safety will focus on reporting information about the seizure proportion in the slow-wean intervention and the difference between seizure proportions in both interventions. At each interim analysis of safety, we will calculate the posterior distribution of seizure proportion within each intervention by using a simple Bayesian logistic regression model, intercept and treatment effect parameters with neutral priors on the intercept and the intervention effect parameter. We will place a normal (Under this guideline, the DSMC may consider stopping the trial for safety, if there is convincing evidence that the seizure proportion among rapid-wean infants is greater than 0.1 and there is convincing evidence that the seizure proportion among rapid-wean infants is more than seven percentage points greater than the seizure proportion among slow-wean infants. Finally, as with efficacy and futility, the DSMC charter states trial stoppage guidelines can be ignored if the DSMC determines it is necessary.