Background: Randomized, double-blind, clinical trials represent the gold-standard for testing efficacy of new compounds or therapies. Randomization distributes subjects evently among treatment groups, thereby minimizing the influence of investigator or patient attributes on outcome measures. Multicenter trials, ascending dose studies, or designs employing stratification by patient characteristics may require multiple randomization tables for each site and stratification factor. This greatly increases chance of error in treatment allocation. We describe a randomization system that was adapted for a pediatric trial. Methods: A multicenter efficacy trial was conducted that required prospective stratification by three clinical parameters and balanced therapy assignment across 15 centers. An untreated reference group was included. Randomization tables blocked in groups of four were generated for each stratum, with a separate table of numbers for the reference group. An algorithm was developed for CORE (Computerized Randomization Enrollment), a telephone randomization system, that allowed the system to assign treatment from a master randomization table. Interactive voice recording technology integrated into CORE allowed users to input patient demography, therapy group (reference or treatment), and stratification level using touch-tone telephone keypads. The system verified inputted data against entry criteria, and assigned a unique identifier and associated treatment. The system also confirmed treatment assignments by fax and tracked subject withdrawals. The sponsor's study personnel could access study enrollment status through their network based computers.

Discussion: We describe a software solution that was adapted for a pediatric multicenter efficacy trial. It allowed for a stratified, site-independent, randomization scheme that distributed therapy assignments across all sites. Such systems will facilitate more efficient clinical trials by minimizing errors in treatment assignment, and improving study tracking. These benefits may also result in faster answers to research questions, thereby rendering the trials more ethical.

{\i Sponsored by Wyeth-Ayerst Research.}