In the present issue of Annals of Surgery, Tambone et al1 from the University of Rome describe a proposal for determining if a sham surgical arm in a clinical trial is acceptable on the basis of both ensuring the safety of subjects and ensuring that they are treated in an ethically appropriate manner. For many surgeons, the very discussion of a sham surgical arm for a clinical trial raises significant ethical concerns. All surgery carries risks and thus a sham operation puts subjects at risk with no possibility for benefit. The prospect of such a situation will seem to many to be the very definition of unethical behavior. However, the ethical evaluation of sham surgery requires attention to the specific context in which it is being raised.
All physicians realize that the current gold standard for evidence is a prospective, double-blind, placebo-controlled randomized trial. The use of a placebo drug (a “sugar pill”) is well-accepted and carries no risks to the subject. In order to know if subjects report benefit due to the placebo effect rather than to the drug itself, it is necessary to have a placebo control arm. In surgery, it is certainly more difficult to have a sham surgery arm than to give a subject a sugar pill, but as many authors have argued in the past, there is a significant benefit in determining the true value of an operation as compared with the placebo effect of an operation.2 As far back as 1961, Henry Beecher noted that many patients could be saved from ineffective and potentially dangerous operations if surgical procedures were tested against placebo operations.3 Thus, even though a sham operation as part of a clinical trial does place the subject at some risk, the potential benefits of knowing if an operation is actually better than a placebo are thought to outweigh the risks to the subjects of the trial.
Tambone et al1 have provided a stepwise method for determining whether it will be safe and ethical to have a sham surgery arm in a clinical trial. These authors suggest evaluating 4 aspects of a clinical trial in which a sham surgical arm is proposed. First, in order for a sham operation to be a reasonable arm of a trial, it must be safe for the subject. This entails that there should be no alternative effective surgical therapy and that the sham operation be made as low risk as possible. Second, the methodology of the study must be such that the risks to the subjects who receive the sham surgery are outweighed by the benefits of obtaining the results of the study. In other words, the study must be so well designed that the research questions will be able to be answered by the trial. Third, informed consent must be ensured so that subjects fully understand that if they enroll in the trial, they may receive a sham operation that will have no benefit to them. Fourth, the economic implications of the sham surgery trial must be such that subjects are not charged whether they receive the sham operation or the study operation.
Attention to all of these issues will go a long way toward ensuring that if a clinical trial includes a sham surgery arm, the safety of subjects is protected and they will be treated in an ethically acceptable fashion. Sham surgery trials will continue to raise ethical questions. For example, has the sham operation been designed to place the subject at the least possible risk while still maintaining the appearance to the subject of having the study operation and has the protocol been set up such that the operating surgeon is not being asked to further mislead the subject during the recovery phase?4 Although this “road map” will not solve all of the ethical and safety concerns raised in sham surgery trials, it does provide an organized manner to address the many of the potential ethical issues in a systematic fashion.
1. Tambone V, Sacchini D, Spagnolo AG, et al. A proposed road map for the ethical evaluation of sham (placebo) surgery. Ann Surg
2. Tenery R, Rakatansky H, Providence RI, et al. Surgical “placebo” controls. Ann Surg
3. Beecher HK. Surgery as placebo. A quantitative study of bias. JAMA
4. Angelos P. Sham surgery in research: a surgeon's view. Am J Bioethics