Imbalanced Randomization in Clinical Trials

TL;DR

This paper discusses how unequal randomization in clinical trials, especially non-inferiority trials, can enhance efficiency and provides tools for calculating optimal sample sizes under various conditions.

Contribution

It highlights the importance of optimal, often unequal, randomization strategies in non-inferiority trials and offers a practical tool for sample size calculation.

Findings

Unequal randomization can significantly improve efficiency in non-inferiority trials.

Optimal randomization ratios can differ greatly from 1:1 in certain trial designs.

A web-based tool for sample size calculation is provided.

Abstract

Randomization is a common technique used in clinical trials to eliminate potential bias and confounders in a patient population. Equal allocation to treatment groups is the standard due to its optimal efficiency in many cases. However, in certain scenarios, unequal allocation can improve efficiency. In superiority trials with more than two groups, the optimal randomization is not always a balanced randomization. In non-inferiority trials, additive margin with equal variance is the only instance with balanced randomization. Optimal randomization for non-inferiority trials can be far from 1:1 and can greatly improve efficiency, a fact which is commonly overlooked. A tool for sample size calculation for non-inferiority trials with additive or multiplicative margin with normal, binomial or Poisson distribution is available at http://www.statlab.wisc.edu/shiny/SSNI/.