The Ethics of Sham Surgery in Clinical Orthopaedic Research

Mehta, Samir MD; Myers, Thomas G. MD; Lonner, Jess H. MD; Huffman, G. Russell MD, MPH; Sennett, Brian J. MD

Journal of Bone & Joint Surgery - American Volume:
doi: 10.2106/JBJS.F.00563
Ethics in Practice
Author Information

1 Department of Orthopaedics and Sports Medicine, Harborview Medical Center, 325 9th Avenue, Box 359798, Seattle, WA 98104. E-mail address: samir.mehta@uphs.upenn.edu

2 Department of Orthopaedic Surgery, University of Pittsburgh, Kaufmann Medical Building, 3461 Fifth Avenue, Pittsburgh, PA 15213

3 Booth Bartolozzi Balderston Orthopaedics, Pennsylvania Hospital, 800 Spruce Street 3B Orthopaedics, Philadelphia, PA 19107

4 Division of Sports Medicine, Department of Orthopaedic Surgery, University of Pennsylvania, Penn Sports Medicine Center, Weightman Hall, 235 South 33rd Street, Philadelphia, PA 19104

Article Outline

While other surgical specialties, such as neurosurgery and thoracic surgery, have already broached the ethical discussion surrounding sham surgery as a research method, published discussion regarding the use of the sham orthopaedic model has been limited1. One solution in orthopaedics would be to open up the debate and the decision-making process to the surgeons, as there is no current forum or body to do this2. An essential question in the debate on the ethics of sham surgery concerns resolving the tension between the highest standard of research design (the double-blind, randomized, placebo-controlled trial) and the highest standard of ethics (to do no harm to the patient)3.

We use published orthopaedic studies to analyze the ethical issues that pertain to sham surgery as a methodology in orthopaedic research. In addition, we provide a foundation for the orthopaedic surgeon on the subject of sham surgery as a research tool. Our goal is to advance both the discussion and the understanding of the ethical issues surrounding sham orthopaedic surgery as it applies to orthopaedic surgeons and their patients.

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The Need for Sham Surgery in Orthopaedics

Few physicians and researchers would deny the existence of the sham (placebo) surgery effect. However, the degree to which the placebo effect impacts outcomes is not completely understood. A comprehensive metaanalysis of research on the placebo effect indicated that subjective outcomes can be attributable to “placebo” effects or bias4,5. Therefore, a study that evaluates treatment outcomes should account for the placebo effect5.

These findings are relevant to a discussion involving outcome measures in orthopaedic surgery, as subjective measures such as function and pain are frequently used in clinical orthopaedic studies6,7. These measures are often difficult to gauge objectively. The variable and subjective nature of pain and function lacks the quantifiability of objective measurements such as grip strength or range of motion. The placebo effect can have an impact on subjective measurements, which are less reliable than objective measurements. Therefore, controlling for the placebo effect is an important and critical aspect of experimental design in clinical research.

A second argument in favor of the use of the sham surgical model in orthopaedic surgery includes the need to maintain the blinding of both the physician-researcher and the subjects. The importance of blinding subjects is critical when attempting to control for and more accurately measure placebo effects. Patients have a bias toward favorable outcomes after surgical intervention because patients want to believe that they chose the correct option for their care8,9. This “leap of faith” can be greater in surgery than with medical trials, in which the perceived and real risks of the intervention may be more subtle, less severe, and do not involve the pain and risks of invasive procedures. Additionally, investigator bias needs to be minimized through blinding of the physician-researcher. It is difficult to conceal radiographs, incisions, scars, effusions, and abnormalities of gait—all of which can alert the surgeon to the treatment the patient received (surgery or no surgery). Thus, the study evaluator and the surgeon may need to be two distinct entities.

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Ethical Considerations Surrounding Sham Surgery

An interesting argument has been forwarded regarding the double standard that now exists between medical and surgical trials3,10. This double standard attempts to explain the accepted use of placebo controls in drug trials, while questioning its use in surgical trials. It has been argued that sham surgery fails to minimize the risk of harm to the subjects and thus fails to make a valid claim to be ethically equivalent to a drug trial.

However, a review of the literature reveals no arguments against the use of sham operations in surgical trials from a scientific methodological standpoint. All arguments against sham surgery are grounded in the ethics of performing sham surgery. Even advocates against the sham surgical model have acknowledged that the double-blind, randomized, placebo-controlled study is the so-called gold standard of research design in reference to methodological rigor3,11.

The criticism of sham surgery involves three issues. The first issue is the tension between the highest standard of clinical research design—the randomized, blinded, placebo-controlled study—and an ethically designed clinical trial. This concept is rooted in the idea of minimizing risks to a subject, implying that a randomized, blinded, sham surgical design cannot be ethical because it fails to minimize patient risk. The second issue revolves around the risk-to-benefit ratio of the subjects involved in the research study. The third point of controversy involves the relationship between the risks to the subjects and the subjects' level of informed consent.

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Minimizing Risks

The surgeon-researcher must maintain the highest standard of ethics while simultaneously preserving clinical research design. The argument has been made that performing a surgical procedure that has no expected benefit other than the placebo effect violates the ethical and regulatory principle that the risk of harm to subjects must be minimized in the conduct of research3.

However, the Code of Federal Regulations only requires that risks to subjects be “minimized”—not eliminated. The Code of Federal Regulations is a compilation of all federal regulations (including regulatory issues regarding research), signed by the Executive Office of the federal government of the United States, published on an annual basis. One specific section of the Code (45 CFR 46), entitled “Protection of Human Subjects” under the Department of Health and Human Services, provides specific guidelines that researchers must follow and institutional review boards must enforce. The guidelines do not state that interventions must have “potential therapeutic benefit.” 12-14

For example, in the sham-controlled arthroscopic knee surgery trial described by Moseley et al., the subjects had failed “maximal medical treatment” for osteoarthritis for at least six months15. The patients were divided into three groups: a placebo (sham) surgery group, an arthroscopic lavage group, and an arthroscopic débridement group. The sham surgery group had incisions made, but no instruments entered the portals for arthroscopy. Postoperative care delivered to the sham surgery group was identical to the care provided to the surgery group. Indeed, there was a net risk on the part of the research subjects in this study, namely, the risk of infection from the surgical site and the risk of an adverse reaction from the anesthesia, but these risks were minimized as the Code of Federal Regulations requires.

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Assessing Risks and Benefits

In evaluating risks and benefits, the institutional review board plays a critical role. At most institutions, the institutional review board consists of physicians, statisticians, researchers, community advocates, and others who ensure a clinical trial is ethical and that the rights of study participants are protected. Nearly all clinical trials in the United States must be approved by an institutional review board before they begin. When evaluating the merits of a study, the institutional review board should consider not only the risks and benefits that may result from the research but also the possible long-range effects of applying knowledge gained in the research as among the research risks that fall within the purview of its responsibility. However, the onus lies on the clinical researcher to design a study and ask a question that minimizes the risk to study subjects.

One such example from the literature of an invasive technique that confers no benefit and the potential for harm to subjects is a study by Palmieri et al., in which ten healthy volunteers allowed their knees to be injected with 10 mL of saline solution to simulate the effects of a knee effusion on muscle function16. Both the study by Moseley et al. and the study by Palmieri et al. involved physical intervention to answer clinical questions that the authors were unable to answer as convincingly by means of any other method of study. Both studies could have been rejected by their respective institutional review boards because both study groups had nothing to gain by participating in the study.

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Informed Consent

Informed consent is the cornerstone of clinical research12. The Belmont Report stated that a proper informed consent requires three components: information regarding the planned procedure, a clear comprehension of the potential risks and benefits by the subject, and the ability of a subject to knowingly volunteer17. These same components are true when one obtains consent from patients in a study that includes sham surgery. The informed consent should be obtained without coercion, should be nonbiased, and should be administered by staff who are knowledgeable about the procedure18-21.

The study by Moseley et al. introduced a novel and exemplary safeguard against improper informed consent and required all subjects who entered the study to write in their chart, “On entering this study, I realize that I may receive only placebo surgery. I further realize that this means that I will not have surgery on my knee joint. This placebo surgery will not benefit my knee arthritis.”15,22

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Sham Orthopaedic Trial Design

Sham surgery has a role in orthopaedics as a research method if researchers who use this methodology minimize risks, ensure an appropriate risk-benefit ratio, and provide informed consent. Obviously, there may not be a single rule or guideline defining an ethical sham-controlled orthopaedic study. We propose a multistep process to ensure that shamcontrolled surgical trials in orthopaedics are performed in an ethical manner. The five-step checklist in Table I can be applied to any potential orthopaedic research proposal. This list seems to apply best to the issues of minimizing risk and the risk-benefit ratio10,23.

One reason for requiring proof of procedure efficacy compared with a benign placebo control is that subjects are spared the possible unnecessary complications associated with sham orthopaedic surgery. In a relatively benign or minimally invasive sham orthopaedic surgical procedure, violation of this rule may not seem to be very alarming. However, the risk of complications and problems in patients involved in an orthopaedic surgical trial with a much higher risk-to-benefit ratio (e.g., spinal fusion) becomes more concerning. In this light, some might argue that the only orthopaedic surgical procedures that can be part of a sham trial are those that are minimally invasive.

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Overview

Sham surgery is a research method that, when applied appropriately, can be a powerful tool to answer a specific well-designed question. Sham-controlled orthopaedic research should be designed with the following ethical ideals in mind: minimizing risks, assessing the risk-to-benefit ratio, and imparting an appropriate informed consent22,24,25. Quelling doubts regarding the use of sham orthopaedic surgery as a research tool will hopefully provide orthopaedic practitioners with superior data allowing for the practice of evidence-based medicine. The greater resource of evidence-based medicine provided by sham-controlled orthopaedic surgery studies will raise the standard of orthopaedic care to the level that the public deserves. One thing is certain—sham orthopaedic surgery needs to be validated as a research method26.

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

1. , Buckwalter JA. Randomized surgical trials and “sham” surgery: relevance to modern orthopaedics and minimally invasive surgery. Iowa Orthop J. 2006;26: 107-11.
2. . Social aspects of sham surgeries. Am J Bioeth. 2003;3: 70-1.
3. . The ethical problems with sham surgery in clinical research. N Engl J Med. 1999;341: 992-6.
4. , Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med. 2001;344:1594-602. Erratum in: N Engl J Med. 2001;345: 304.
5. , Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2004;3: CD003974.
6. , Phillips CB, Poss R, Harrast JJ, Fossel AH, Liang MH, Sledge CB. The validity and reliability of a Total Hip Arthroplasty Outcome Evaluation Questionnaire. J Bone Joint Surg Am. 1995;77: 1528-34.
7. , Beaton DE, Richards RR. Validity of observer-based aggregate scoring systems as descriptors of elbow pain, function, and disability. J Bone Joint Surg Am. 1998;80: 154-62.
8. . Ethical requirements that must be met before the introduction of new procedures. Clin Orthop Relat Res. 2000;378: 15-22.
9. . Ethical standards in the treatment of human subjects involved in clinical research. J Pediatr Orthop. 1998;18: 701-2.
10. . Placebo surgery for Parkinson's disease: do the benefits outweigh the risks? J Law Med Ethics. 2002;30: 58-68.
11. . Placebo surgery research: a blinding imperative. J Clin Epidemiol. 2006;59: 876-80.
12. , Wendler D, Grady C. What makes clinical research ethical? JAMA. 2000;283: 2701-11.
13. , Lemaire F. Ethics and research in critical care. Intensive Care Med. 2006;32: 1697-705.
14. . Defending the distinction between research and medical care. Am J Bioeth. 2006;6: 63-6.
15. , O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, Hollingsworth JC, Ashton CM, Wray NP. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347: 81-8.
16. , Ingersoll CD, Cordova ML, Kinzey SJ, Stone MB, Krause BA. The effect of a simulated knee joint effusion on postural control in healthy subjects. Arch Phys Med Rehabil. 2003;84: 1076-9.
17. Protection of human subjects; Belmont Report: notice of report for public comment. Fed Regist. 1979;44: 23191-7.
18. , Looman JE, Lewis SK. Informed consent: is it a myth? Neurosurgery. 1992;30: 453-8.
19. , Napier A, Cuschieri A. How informed is signed consent? Br Med J (Clin Res Ed). 1988;296: 839-40.
20. . Medical research and the human subject. Problems of consent and control in the UK experience. Ann NY Acad Sci. 1988;530: 144-53.
21. . Informed consent. Clin Orthop Relat Res. 2000;378: 71-7.
22. . Sham surgery: an ethical analysis. Am J Bioeth. 2003;3: 41-8.
23. , Kadane JB. Sham surgery and genuine standards of care: can the two be reconciled? Am J Bioeth. 2003;3: 61-4.
24. . Arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347: 1717-9.
25. . Arthroscopic surgery was not effective for relieving pain or improving function in osteoarthritis of the knee. ACP J Club. 2003;138: 49.
26. , Moreno JD. Surgical research, an elusive entity. Am J Bioeth. 2003;3: 49-50.
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