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Controlled Trials: descriptions Other
Surgery |
Placebo controlled trials are needed in a few well selected conditions
Surgical technology has advanced exponentially in recent years, although our attitudes toward its introduction into contemporary practice remain archaic. Whereas strict licensing regulations exist for all novel prescription drugs, surgical innovation is assimilated relatively unchecked. Minimal access technologies have represented a particular problem. Previously, the mainstay of surgical innovation centred on technical modification of standard procedures of surgical care. The studies were therefore based on comparison with gold standard and rarely placebo or sham operations. The advent of minimal access methods, with their promise of reduced trauma associated with surgery, has led to a large increase in proposed roles for surgery, although, as for many current gold standards in surgery, a foundation of robust evidence is lacking.
Moseley and colleagues' recent study has once again raised the spectre of
placebo controlled trials in surgery.1 They found
that arthroscopic intervention for osteoarthritis of the knee
had no increased therapeutic benefit compared with placebo operation.
This is an important example, not only for people with osteoarthritis,
but for the surgical community in general, who perform such operations
without any controlled data to suggest efficacy. This article
focuses on examining the ethical and scientific issues of trials
involving sham surgery and the implications for comparison studies in
current frameworks for modern surgical treatments.
Ethical issues
Surgery by its nature does not lend itself readily to placebo
controlled trials as sham operations engender invasive procedures
with the possibility of non-trivial morbidity. This raises
fundamental ethical objections regarding the responsibility of the
researcher to act in the subject's best interest,2
and the semi-intuitive tenet that invasive surgery should be reserved
for situations where significant benefit is associated with minimised
or minimal risk. In the case of sham surgery the risk of harm
is associated with negligible potential benefits. This has been the
main area for attack by professionals who are opposed to placebo
surgery. Although there are no definitive answers to these views, we
should not confound the ethics of clinical research with those of
clinical care.3 A randomised placebo controlled
trial is not an individualised care regimen but a respected
scientific tool to discern best treatment and benefit for a future
cohort. Whether the study subjects receive benefit by omission or
commission is, by its nature, random. Thus, although this is perhaps
Machiavellian, studies should be conducted according to the ethics
governing clinical research, which lessen debate regarding unique
surgical concerns in these trials but do not undermine basic ethical
frameworks when dealing with human subjects.4
Scientific issues
The practical aspects regarding the design of placebo controlled
surgical trials largely follow from ethical concerns. Obviously the
scientific question should be valuable, any risks involved should be
minimised, and all included in the study should have given validated
informed consent. One of the major issues will be whether comparison
with placebo is a justifiable design. Moseley and colleagues'
research illustrates the applicability of a placebo trial in the
assessment of efficacy in a non-life threatening condition where the
standardised role of surgery is unclear. Application of sham trials
to more complex areas would be more difficult, and it would be mostly
prohibitive with respect to oncological surgery. Although no sham
controlled evidence exists to support the use of surgery in the
resection of solid tumours, it would be wholly unreasonable to design
placebo trials, given our knowledge about progression of tumours in
the absence of treatment.
Implications for comparison studies for the introduction of
novel techniques
Given the obvious ethical controversy as well as the many pitfalls
that design may hold, it is amazing that any such trials are
conducted today. They do provide, however, exemplary evidence when
pitched against standard controlled studies. Many such standards lack
a foundation of evidence and are accepted on historical status alone.
Particularly in the light of recent and past revelations in trials
involving sham surgery, the surgical community should critically
evaluate itself regarding the efficacy of individual operations
performed. The role for comparative analysis will remain paramount in
this field although we should strive for excellence in design and
take into account the deficiencies in the evidence from existing gold
standards.
We do not suggest that placebo controlled surgical trials are a ubiquitous tool for validation of novel surgical technologies and techniques. We believe that many such trials will continue to focus on comparison with current standards. We do think that surgical innovation that has not previously been associated with robust scientific validation should be evaluated by placebo controlled trials in selected conditions, especially where subjective symptoms of the patient are relied upon as outcome measures. We also caution that the Hippocratic principle of "first do no harm" requires individual interpretation when designing placebo controlled surgical trials.
Paul F Ridgway
Ara W Darzi
(a.darzi@ic.ac.uk), Department of
Surgical Oncology and Technology, Imperial College Faculty of Medicine, St
Mary's Hospital, London W2 1NY
Footnotes
The views expressed in this editorial are those of the authors and do not necessarily reflect those of any regional, national, or international healthcare bodies.
Competing interests: None declared.
| 1. | Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002; 347: 81-88[Abstract/Full Text]. |
| 2. | Clark PA. Placebo surgery for Parkinson's disease: do the benefits outweigh the risks? J Law Med Ethics 2002; 30: 58-68[Medline]. |
| 3. | Horng S, Miller FG. Is placebo surgery unethical? N Engl J Med 2002; 347: 137-139[Full Text]. |
| 4. | Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000; 283: 2701-2711[Medline]. |
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Collections under
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Controlled Trials: descriptions Other
Surgery |
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