Randomization and allocation concealment: a practical guide for researchers

Abstract

Although the randomized controlled trial is the most important tool currently available to objectively assess the impact of new treatments, the act of randomization itself is often poorly conducted and incompletely reported. The primary purpose of randomizing patients into treatment arms is to prevent researchers, clinicians, and patients from predicting, and thus influencing, which patients will receive which treatments. This important source of bias can be eliminated by concealing the upcoming allocation sequence from researchers and participants. Although there are many approaches to randomization that are known to effectively conceal the randomization sequence, the use of sequentially numbered, opaque sealed envelopes (SNOSE) is both cheap and effective. The purpose of this tutorial is to describe a step-by-step process for the preparation of SNOSE. We will outline how to prepare SNOSE to preserve allocation concealment in a trial that (a) uses unrestricted (simple) randomization, (b) stratifies randomization on one factor, (c) uses permuted blocks and, and (d) is conducted at more than 1 study site.