Scientific challenges in the application of randomized trials

Abstract

In recent years, scientific challenges in the application of randomized trials have become more apparent, especially with the extension of such trials to the assessment of nondrug treatments, such as health education, psychotherapy, and health care provision. Six issues (individualvgroup randomization, blinding and unblinding, the effect of trial participation on outcome, selective subject participation, treatment compliance, and standardizedvindividualized treatment) are discussed in terms of their impact on internal validity, generalizability (external validity), and clinical relevance. Specific design strategies may be necessary to enhance these methodological and clinical desiderata. Attention to these challenges should lead to improvements in future randomized trials. (JAMA1984;252:2739-2745)