The ethical problem of randomization.

Abstract

The Fondazione Umberto Veronesi ethics committee recently published a statement concerning the inherent ethical issues of randomized clinical trials (RCTs), mainly focusing on randomization, raising many questions, and suggesting possible solutions. The main concern is that the patients enrolled in a RCT are used to improve medical knowledge, but they cannot be the beneficiaries of the results of the trials in which they are participating. Possible solutions come from a wider use of clinical and administrative databases, and an early termination of trials. We discuss this statement, emphasizing that the scientific and ethical reason for embarking on a clinical trial is uncertainty. The uncertainty regarding the comparative benefits and harms of each compared treatment (clinical equipoise) warrants equity in allocation. Randomization allows one to obtain unbiased evidence that we cannot know in advance. The expected probability of a new treatment to be successful describes the limits within which a study can be acceptable both from an ethical as well as a scientific point of view. Most people accept enrollment in a RCT if the probability of success of the experimental treatment is between 50 and 70%. The assumption and concern that there is a conflict between "scientific" and "ethical" aspects of a clinical trial due to randomization should at least be mitigated, considering that only scientifically sounded studies can be considered ethical. Randomization remains the appropriate approach to ensure the study's internal validity. Different aspects seem to be more important, from the ethical point of view, considering RCT and their publication.