Bounded-width confidence interval following optimal sequential analysis of adverse events with binary data.

In sequential testing with binary data, sample size and time to detect a signal are the key performance measures to optimize. While the former should be optimized in Phase III clinical trials, minimizing the latter is of major importance in post-market drug and vaccine safety surveillance of adverse events. The precision of the relative risk estimator on termination of the analysis is a meaningful design criterion as well. This paper presents a linear programming framework to find the optimal alpha spending that minimizes expected time to signal, or expected sample size as needed. The solution enables (a) to bound the width of the confidence interval following the end of the analysis, (b) designs with outer signaling thresholds and inner non-signaling thresholds, and (c) sequential designs with variable Bernoulli probabilities. To illustrate, we use real data on the monitoring of adverse events following the H1N1 vaccination. The numerical results are obtained using the R Sequential package.

The effect of two different doses of dexmedetomidine to prevent emergence agitation in children undergoing adenotonsillectomy: a randomized controlled trial.

OBJECTIVE: To evaluate different doses of dexmedetomidine for the prevention of emergence agitation in children undergoing adenotonsillectomy. METHOD: One hundred and thirty children aged 3-10 years scheduled for adenotonsillectomy were randomly assigned to two groups. Anesthesia was induced with 0.5 µg.kg-1 dexmedetomidine (DEX 0.5 group) or 1 µg.kg-1 dexmedetomidine (DEX 1 group) at the beginning of surgery. Observers who recorded the data in the postanesthesia care unit were blinded to the allocation. The primary outcome was the percentage of emergence agitation. The times to spontaneous breath, awake, extubate, and postanesthesia care unit stay were also recorded. RESULTS: One hundred twenty four children were randomized into two groups. Five children were excluded because of adverse events and dropout (DEX 0.5 group, n = 58; DEX 1 group, n = 62). No significant differences were noted in the percentage of emergence agitation between the two groups. The times to extubation (p = 0.003), awake, and postanesthesia care unit stay in DEX 0.5 group were shorter than those in DEX 1 group (p < 0.0001). There was no significant difference between the two groups in the time to spontaneous breath. Approximately 8% of patients in DEX 0.5 group and 18% patients in DEX 1 group presented low SpO2, showing a significant difference between the two groups (p = 0.043). CONCLUSIONS: A dose of 0.5 µg.kg-1 dexmedetomidine was equally effective as 1 µg.kg-1 dexmedetomidine in preventing emergence agitation. TRIAL REGISTRATION: The trial is currently completed recruitment, registered in ClinicalTrials.gov (ID:NCT03760809). Inclusion began on 4 January, 2019.