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.
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.
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.
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.
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
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.