Issue: November/December 2005
Research in Action
Placebo brain surgery
It's not ethical - and of little value
During human trails to evaluate new pharmaceutical therapies it is common for participants in
the control group to be given a placebo or sham drug.
This enables the effect of the drug on those who have taken it to be compared with those who
believe they have taken it but have not.
Should the same technique be used with brain surgical trials?
For example, is it appropriate to perform sham or placebo operations to evaluate the safety
and efficacy of neural tissue grafting, a surgical technique used to treat Parkinson's disease?
A La Trobe University researcher and a colleague in social health from the University of Melbourne
are examining this extremely controversial question which takes in both medical ethics and questions
about the efficacy of assessment methods used in trials of novel surgical procedures.
Mr Stephen Polgar, a La Trobe senior lecturer in Public Health, and Ms Joanna Ng, a postgraduate
student at the University of Melbourne, have closely examined the outcomes of four surgical trials
in the USA, three of which involve transplanting cells for patients with Parkinson's disease.
A paper by Mr Polgar and Ms Ng, Ethics, Methodology and the use of Placebo Controls in surgical
trial appeared in the October 2005 edition of the international journal, Brain Research Bulletin.
This is part of a series of publications analysing the methodological and theoretical foundations
for using stem cells to reconstruct the human brain.
'After closely assessing the rationale and methods, we concluded on the basis of the evidence
that sham surgery was not essential and therefore not ethical,' Mr Polgar said.
Mr Polgar explains that neural tissue grafting is an experimental procedure used to treat a
number of neuro-degenerative disorders including Parkinson's disease. Donor embryonic cell tissue
from human embryos is used to reinnervate the brain.
The next phase of the research for reconstructing the human brain will involve trialling the
grafting of various stem cell lines which may prove more clinically effective than embryonic
cells.
Mr Polgar's research specialises in the mechanisms and outcomes of reconstructive neurosurgery
and the importance of rehabilitation for recovery following neural grafting. Ms Ng has an academic
interest in chronic illnesses, ethics and complementary medicine.
Mr Polgar said that American neurosurgeons performed 94 neural grafting procedures, with 40
of these being sham operations. Sham operations involve the same interventions as actual surgery
with exception of delivering the 'active' component of the treatment.
Those who received the sham operations were meant to be the control group against which the
efficacy of the genuine operations could be gauged. In order to maintain a double-blind design,
the surgeons go through the 'street theatre' of pretending to the sedated patients that they
are conducting a genuine transplantation.
Each patient was aware when volunteering to participate in the studies that sham operations
were involved in the trials, but were not aware whether their own operation was genuine or sham.
Mr Polgar and Ms Ng are concerned that the use of sham surgery, which is an active intervention
with obvious risks, is significantly different to the inert placebos used in pharmacological
research.
'Those who carried out the trials were perfectly competent surgeons who believe putting people
through sham surgery contributes to knowledge about outcomes,' Mr Polgar said.
He concedes that sham surgery enables the classic methodologically-rigorous evaluation method
known as a double-blind randomised trial to be used because it is the most effective way to control
for confounding variables such as the placebo effect and investigator bias.
Regardless of the large placebo effects anticipated by the neurosurgeons, a key finding in the
paper was that there was no evidence for placebo effects in the sham-operated patients.
Also, Mr Polgar and Ms Ng found that the poor efficacy of the surgical procedures was evident
without reference to the placebo controls. They concluded that the inclusion of sham operated
control groups does not improve the validity of either statistical or clinical decision making - and
was therefore neither essential nor ethical.
'We contend that the welfare of patients and public safety are not protected by subjecting patients
to sham surgery but rather by demonstrating that a given surgical procedure is the best available
treatment for a disorder'.
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