Simulation-Based Analysis of Trial Design in Regional Anesthesia

TL;DR

This paper uses simulations to show that small sample sizes in regional anesthesia trials are expected and unlikely to change conclusions about new blocks.

Contribution

The study introduces a simulation-based approach to analyze trial design in regional anesthesia research.

Findings

Simulations predict 16 RCTs with a median of 970 patients and no large trials.

Lowering the significance threshold increased patient enrollment but caused early trial termination.

Small sample sizes are rational outcomes of current trial designs in this field.

Abstract

In regional anesthesia, the efficacy of novel blocks is typically evaluated using randomized controlled trials (RCTs), the findings of which are aggregated in systematic reviews and meta-analyses. Systematic review authors frequently point out the small sample size of RCTs as limiting conclusions from this literature. We sought to determine via statistical simulation if small sample size could be an expected property of RCTs focusing on novel blocks with typical effect sizes.

We simulated the conduct of a series of RCTs comparing a novel block versus placebo on a single continuous outcome measure. Simulation analysis inputs were obtained from a systematic bibliographic search of meta-analyses. Primary outcomes were the predicted number of large trials (empirically defined as N ≥ 256) and total patient enrollment.

Simulation analysis predicted that a novel block would be tested in 16 RCTs enrolling a median of 970 patients (interquartile range (IQR) across 1000 simulations: 806, 1269), with no large trials. Among possible modifications to trial design, decreasing the statistical significance threshold from p < 0.05 to p < 0.005 was most effective at increasing the total number of patients represented in the final meta-analysis, but was associated with early termination of the trial sequence due to futility in block vs. block comparisons.

Small sample size of regional anesthesia RCTs comparing novel block to placebo is a rational outcome of trial design. Feasibly large trials are unlikely to change conclusions regarding block vs. placebo comparisons.

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