Sham surgeries serve as placebos in some clinical trials, with researchers performing all steps of an innovative procedure, except those deemed therapeutically necessary. However, sham surgeries have been the subject of ethical scrutiny and debate for years.1-3 During a monthly meeting of a departmental journal club at the MedStar Georgetown University Hospital, clinicians were reviewing a paper about a randomized, controlled trial during which researchers used sham surgery. One of the participants asked, “Are studies like these ethical?” This spurred a heated discussion, and the group decided further analysis was needed.
“Analyzing numerous surgical sham-controlled trials in a systematic way in order to highlight surgical and ethical considerations of these trials had not been done before,” according to Peter Hetzler III, MD, MHS, the study’s lead author and a plastic surgery resident at the MedStar Georgetown University Hospital.
Hetzler and colleagues reviewed 172 sham-controlled studies.4 The most common types of anesthesia were deep and general. Four trials explicitly did not offer the surgery to participants in the sham arm. Nearly two-thirds of trials did not include any mention of whether the intervention was offered. Only about one-third of the studies explicitly documented offering the actual procedure to participants.
“Lack of any documentation on whether or not the actual intervention was offered to the participants at the end of the trial is ethically concerning,” Hetzler says.
For participants randomized to control, placebo, or sham groups, there is a consensus suggesting researchers should offer the actual medication, treatment, or procedure at the conclusion of the trial if the experimental solution is showing better results than placebo.
“Given the importance of this specific moral obligation, this should be documented for all randomized, controlled trials involving sham procedures,” Hetzler stresses.
Another ethical concern involved the surgical indications for the sham-controlled clinical trials. Twenty percent were for pain, 16% were for movement disorders, and 4% were for mental illness. Many participants were suffering from late-stage disease processes, including intractable chronic pain, end-stage Parkinson’s disease, and recalcitrant major depression. “We know that all three of these pathologies can impact patients’ executive functioning,” Hetzler reports.
This limits patients’ ability to effectively assess the risks and benefits of a sham-controlled trial effectively. Thus, about 40% of the studies might have involved patients with less capacity for informed consent. Those patients might be so desperate for any relief or treatment they are essentially “forced” to sign the consent.
“Rather than being forced by researchers to sign the consent, which we would consider an ‘external coercion,’ these patients may be forced by their own disease process and symptoms to sign the consent, which we deem an ‘internal coercion,’” Hetzler explains.
Hetzler and colleagues concluded there are legitimate ethical concerns when investigators conduct sham-controlled trials to identify the efficacy of invasive procedures. On one hand, researchers need a way to effectively determine if the surgery actually works.
“On the other hand, given the inherent invasive nature of surgeries, designing ethically sound and efficacious clinical trials is exceedingly difficult,” Hetzler admits.
The authors acknowledged there is a place for sham-controlled surgical trials. However, such studies require more stringent evaluation and regulation than placebo-controlled trials involving medications, which are inherently less invasive interventions.
“This is especially true when it comes to determining the patient population and surgical indications of a sham-controlled trial,” Hetzler says.
Researchers should carefully consider the informed consent process when vulnerable patient populations, and patients who are undergoing emergent interventions, are studied. “These patients are more likely to agree to participate in a study that may not be in their best interest, given their medical condition or circumstance,” Hetzler explains.
REFERENCES
1. Polgar S, Mohamed S. Evidence-based evaluation of the ethics of sham surgery for Parkinson’s disease. J Parkinsons Dis 2019;9:565-574.
2. Miller FG. Sham surgery: An ethical analysis. Sci Eng Ethics 2004;10:157-166.
3. Horng S, Miller FG. Ethical framework for the use of sham procedures in clinical trials. Crit Care Med 2003;31:S126-S130.
4. Hetzler PT 3rd, Berger LE, Huffman SS, et al. The characteristics and ethics of sham surgeries: A systematic review of randomized controlled trials. Ann Surg 2023; Apr 17. doi: 10.1097/SLA.0000000000005882. [Online ahead of print].
There are legitimate concerns when investigators conduct sham-controlled trials. Researchers need a way to effectively determine if the surgery works, but designing this kind of ethically sound and efficacious clinical trial is difficult.
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