Advantages and Drawbacks of the Zelen Design for Randomized Clinical Trials

I N a randomized clinical trial, which is the accepted scientific standard for the evaluation of therapeutic efficacy, a new or improved therapeutic agent is directly compared to a placebo or standard treatment. In the conventional design of such a study (Fig. 1), patients who meet certain admission criteria are considered eligible for participation in the trial. After informed consent is obtained, patients are assigned by a random (or chance) mechanism to receive either of the compared therapies. Some investigators and patients may be reluctant to participate in such randomized clinical trials. This reluctance arises in part from use of the chance mechanism that precludes clinical judgment for the assignment of treatment and from the requirement, in double. blind trials, that neither the physician nor the patient can know which therapy the patient will receive. Marvin Zelen, writing in the New England Journal of Medicine,1 offered an alternative way to plan randomized clinical trials. The principal advantage of his new design is that both the patient and the physician know, before consent is obtained, whether the experimental treatment was assigned. The new design is illustrated in Fig. 2. Eligible patients