Minimal sufficient balance--a new strategy to balance baseline covariates and preserve randomness of treatment allocation

In many clinical trials, baseline covariates could affect the primary outcome. Commonly used strategies to balance baseline covariates include stratified constrained randomization and minimization. Stratification is limited to few categorical covariates. Minimization lacks the randomness of treatment allocation. Both apply only to categorical covariates. As a result, serious imbalances could occur in important baseline covariates not included in the randomization algorithm. Furthermore, randomness of treatment allocation could be significantly compromised because of the high proportion of deterministic assignments associated with stratified block randomization and minimization, potentially resulting in selection bias. Serious baseline covariate imbalances and selection biases often contribute to controversial interpretation of the trial results. The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial and the Captopril Prevention Project are two examples. In this article, we propose a new randomization strategy, termed the minimal sufficient balance randomization, which will dually prevent serious imbalances in all important baseline covariates, including both categorical and continuous types, and preserve the randomness of treatment allocation. Computer simulations are conducted using the data from the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial. Serious...
Source: Statistical Methods in Medical Research - Category: Statistics Authors: Tags: Articles Source Type: research