A New Design for Randomized Clinical Trials

TLDR

The paper proposes a new method for planning randomized clinical trials. The method randomizes patients into two groups, offers the experimental therapy to the second group, and if declined, assigns them to standard care, with all second‑group participants compared to the first group regardless of acceptance. Loss of statistical efficiency can be offset by larger sample sizes, and the design allows patients to know before consent whether they will receive experimental treatment. N Engl J Med 300:1242–1245, 1979.

Abstract

Abstract This paper proposes a new method for planning randomized clinical trials. This method is especially suited to comparison of a best standard or control treatment with an experimental treatment. Patients are allocated into two groups by a random or chance mechanism. Patients in the first group receive standard treatment; those in the second group are asked if they will accept the experimental therapy; if they decline, they receive the best standard treatment. In the analyses of results, all those in the second group, regardless of treatment, are compared with those in the first group. Any loss of statistical efficiency can be overcome by increased numbers. This experimental plan is indeed a randomized clinical trial and has the advantage that, before providing consent, a patient will know whether an experimental treatment is to be used. (N Engl J Med 300:1242–1245, 1979)