Editor’s Commentary: Ethics in Clinical Research

Abstract

Ethics are often thought of as ‘‘something for someone else to be concerned about.’’ Nothing could be further from the truth. Everyone involved in clinical research must be concerned with ethics, whatever his or her role in the overall spectrum of medical product development. Identification of areas in which the highest ethical conduct is paramount is easier in some cases than others. Consider the manner in which subjects participating in clinical trials must be treated. Guiding ethical principles include clinical equipoise, respect for persons, beneficence, and justice. Clinical equipoise exists when all of the available evidence about an investigational drug does not show that it is more beneficial than an alternative and, equally, does not show that it is less beneficial than the alternative. For example, to be able to conduct a clinical trial that involves administering a drug to some individuals and a control treatment (often a placebo) to others, there cannot be any evidence that suggests the investigational drug shows greater efficacy than the control treatment or that it leads to greater side effects than the control treatment. When individuals agree to participate in a clinical trial they do so with the understanding that all of the treatments in the trial are assumed to be of equal value. By the end of the trial (or at the time an interim analysis is conducted, discussed in due course), there may be compelling evidence that the drug is acceptably safe and more effective than the control treatment, but the trial must be started with a good faith belief that the drug and the control treatment are of equal merit. The second principle, respect for persons, necessitates that investigators give potential subjects all pertinent information about the study and answer any questions. If an individual then agrees to participate voluntarily (ie, he or she is not coerced in any real or implied manner), informed consent is obtained. This involves obtaining the subject’s written permission (or the written permission of a parent or guardian) to participate in the study. It also necessitates protecting subjects with possibly impaired decision-making capacity and maintaining confidentiality of all information obtained at every stage of the study procedures. The principle of beneficence requires that the study design is scientifically sound and that any risks of the research are acceptable in relation to the likely benefits from the study at the public health level, and the principle of justice requires that the burdens and benefits of participation in clinical trials are distributed evenly and fairly. Historically, populations that were easily and conveniently accessed by researchers, such as prison inmates, nursing home residents, and people with poor access to general health care, have been used when they should not have been. Vulnerable populations should not be deliberately chosen for participation in clinical trials when nonvulnerable populations would also be appropriate. The benefits of participation, such as access to potentially lifesaving new therapies, should be available to all, including those not historically well represented, such as women, children, and members of ethnic minorities. These principles are well known, appearing in many textbooks addressing clinical research. Less well addressed, but absolutely as important, are the ethical considerations inherent in scientific and operational aspects. Derenzo and Moss commented as follows: