Problems in the Conduct and Analysis of Randomized Clinical Trials

Abstract

To achieve the goal of validity, the randomized clinical trial has emerged as the scientific "gold standard" for evaluating therapies in clinical medicine. Regardless of how well randomized clinical trials are designed, however, problems often occur during the conduct of the trials that give rise to methodologic challenges in the analysis of results. Primarily two types of problems, changes in intended treatment and the failure to ascertain the study outcomes, occur during the conduct of randomized clinical trials. We studied the current analytic strategies that are used to deal with these problems and how the use of these analytic strategies can change the focus of the research so that the trial no longer answers the relevant question. To ensure that the right question is answered, new methods of design and analysis are required that balance the goals of validity and clinical pertinence. (Arch Intern Med.1992;152:507-512)