Design of Randomized Controlled Trials

Abstract

A major factor in the rapid advance of medical science over the past 50 years has been the development and refinement of the clinical research method known as the randomized controlled trial (RCT). A clinical trial is defined as a prospective scientific experiment that involves human subjects in whom treatment is initiated for the evaluation of a therapeutic intervention. In an RCT, each patient is assigned to receive a specific treatment intervention by a chance mechanism. Nothing more clearly indicates the key role of an RCT in modern clinical research than the placement of this specific research method at the top of the list of levels of evidence in evidence-based medicine.1 According to this classification, significant results of an RCT are more definitive than any other type of clinical research information. The purpose of this article is to present an overview of the design of RCTs. Some of the principles of a high-quality study, such as the use of randomization, placebos, and double-blind designs are well known. Other principles such as stratification, use of a decision-making structure, and statistical power are known by many investigators but are not universally recognized or fully understood. These features plus others that indicate the design of a high-quality RCT are discussed. A companion article on the conduct and evaluation of RCTs will appear in a future issue of this journal. One of the most easily recognized aspects of a well-designed and conducted clinical trial is the apparent clarity of the research mechanism evident in its published report. Alternatively, one of the more common problems with a published clinical trial is the apparent “design by committee” in which different members of a protocol team have different goals. Because a clinical trial is a resource-intensive undertaking, many investigators feel that the study should attempt to …