Review of randomised trials using the post-randomised consent (Zelen's) design

Background: In 1979, Zelen described a trial method of randomising participants before acquiring consent in order to enhance recruitment to clinical trials. The method has been criticised ethically due to lack of consent and scientifically due to high crossover rates. This paper reviews recent published trials using this method and describes the reasons authors gave for using the method, examines the crossover rates, and looks at the quality of identified trials. Methods: Literature review searching for all citations to the relevant Zelen's papers of trials published since 1990 plus inclusion of trials from personal knowledge. Results: We identified 5 8 relevant trials. The most common justification for the use of Zelen method was to avoid the introduction of bias (e.g., to avoid the Hawthorne effect). Few trialists had explicitly used the design to enhance participant recruitment. Most trials (n=41) experienced some crossover from one group to the other (median crossover=8.9%, mean= 13.8%, IQR 2.6% to 15%) although this was usually within acceptable limits. Conclusion: The most important reason stated by authors for using Zelen's method was to limit bias. Zelen's method, if carefully used, can avoid 'resentful' demoralisation' and the Hawthorne effect biasing a trial. Unlike a previous review, we found that crossover was not a problem for most trials. (c) 2005 Elsevier Inc. All rights reserved.