Clinical equipoise

The mission of clinical research is to provide scientifically appropriate and accurate information about new treatments in patients, keeping the safety of the patient as absolute priority referring to the law of Hippocrates Nil nocere (Not to harm). An additional ethical aspect of clinical research is the demand of high scientific standards. Therefore ... at the start of the trial, there must be a state of clinical equipoise regarding the merits of the regimens to be tested, and the trial must be designed in such a way as to make it reasonable to expect that, if it is successfully conducted, clinical equipoise will be disturbed (Freedman, 1987). 

Clinical equipoise and informed consent raise issues of beneficence and nonmaleficence, both of which may be violated by participation in the study. However, if there is intent to do good and to avoid harm, then arguably these concerns are satisfied. 

Russell JA. Vasopressin in septic shock Clinical equipoise mandates a time for restraint. Crit Care Med 2003 31 2707-2708. 

Several fundamental ethical principles guide clinical trials, including clinical equipoise, respect for study participants, beneficence, and justice. These are summarized here in turn. 

Clinical equipoise exists when all of the available evidence about a new drug does not show that it is more beneficial than an alternative and, equally, does not show that it is less beneficial. For example, to be able to conduct a clinical trial that involves administering a drug to some participants and a control treatment (sometimes a placebo and sometimes a comparator that is also biologically active)... 

Although discussed in detail elsewhere in this book, the two ethical principles guiding informed consent are those of autonomy and equipoise. Autonomy is the concept that the patient is an individual that is under no duress, whether subtle or obvious, actual or inferred, and is competent to make a choice according to his or her free will. Clinical trials conducted on persons in custody, or on subordinate soldiers, may both be violations of the patient s autonomy. Equipoise is the concept that the investigator, and those sponsoring the trial, are truly uncertain as to the outcome of the study in practical terms, this is a guarantee to the patient that an unreasonable hazard cannot result from unfavorable randomization because the treatment options are not known to be unequally hazardous. 

Clearly, other chapters in this book could have appeared in this section. An early chapter in this book is on informed consent its location is designed to indicate the supervening importance of that particular application of autonomy, beneficence and equipoise. Ethical behavior is also at the very centre of good clinical practices . The chapter on publishing clinical trials also examines some of the ethical aspects of that activity. Dr Belsey also enters into this area with his chapter on advertising and marketing . 

It is perhaps also worth noting that the fact that experimental treatments are not generally available to physicians means that it is not necessary for a physician to be in equipoise for it to be practically ethical for him to participate in a randomized clinical trial. Indeed, it is simply necessary for him not to believe in the inferiority of the experimental treatment. As long as he believes that the experimental treatment is superior, by refusing to randomize and not participating in the trial he condemns all of his patients to receive the treatment he believes is inferior. His participation in the trial is therefore logical until the moment when the new treatment is proved inferior (Senn, 2001, 2002). Thus, without some special arrangement to continue to receive the experimental treatment, there is never any reason for him to withdraw his patients... 

Freedman B (1987a). Equipoise and the ethics of clinical research. N Engl J Med 317 141-145. 

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