New York (MedscapeWire) Mar 23, 2002 The ethical dilemma surrounding placebo surgery has been eclipsed by the controversial use and failure of stem cell therapy in 2 Parkinson's disease (PD) studies.
News of the most recent setback in PD research was released on March 16 when the Genzyme Corporation and Diacrin Inc. reported that in preliminary results from phase 2 clinical trials, no significant improvement resulted from implanting the fetal cells of pigs into patient brains when compared with subjects who received placebo surgery.
In the study, which will be presented at the 14th International Congress on Parkinson's Disease in July, in Helsinki, Finland, 8 of 18 patients had holes drilled into the sides of their heads, but were not given implants. Antibiotics, standard fare for transplant recipients, were administered to all patients, although those who had sham surgery were issued dummy anti-rejection drugs.
The ethics review board at Columbia-Presbyterian Medical Center in New York declined to let their investigators participate in the study because dummy antibiotics could not be provided. The review board deemed the antibiotics provided to all patients as unnecessary, and possibly harmful.
The second recent PD study, conducted by Curt Freed, MD, and colleagues from the University of Colorado Health Sciences Center and published in the New England Journal of Medicine on March 8, was fraught with ethical controversy not because sham surgery was conducted on 20 of 40 patients, but due to the fact that investigators used stem cells from aborted human fetuses and because older subjects receiving injections actually reported a worsening of their conditions. The cultured mesencephalic tissue triggered an overproduction of dopamine in 5 patients, causing them to experience dystonia and dyskinesias.
Although the research into PD itself has been set back by these findings, use of placebo-surgery-controlled trials in neurologic research has become more firmly established. Indeed, the item received only cursory mention in editorial comments in the NEJM and the mainstream media.
Moreover, phony procedures have been seeing wider application across other specialties. For instance, interest in such methods by orthopaedists has been strong at least as long ago as 1996, when a study by J. Bruce Moseley, MD, and colleagues was published in the American Journal of Sports Medicine. Moseley and colleagues reported that subjects who underwent a fake operation had the same levels of relief from osteoarthritis as those who had received arthroscopy.
The American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS), the only medical organization with a policy statement on the procedure, sanctioned sham surgery in January 2000. They state, "in certain, specific neurological conditions, the use of 'placebo surgery' may reduce investigator and patient bias in analyzing treatment outcome and, therefore, increase the likelihood that results of a trial will be interpreted correctly."
In spite of the AANS/CNS endorsement of sham surgery trials as being more methodologically rigorous, medical ethicists remain divided. In a 1997 editorial in the NEJM, Ruth Macklin, PhD, from the Albert Einstein College of Medicine in New York City, noted that performing the procedure for no other objective than to further an experiment violated the principles of "first do no harm."
The first findings on placebo surgery were published in the NEJM in 1959. Leonard A. Cobb, MD, operated on 17 people suffering from angina, tying the arteries of 8 subjects a procedure known as the Fieschi technique and only making incisions in the 9 other patients. The fake procedure now known as internal mammary artery ligation proved as successful as the real ones.
N Engl J Med. 2001;344:710-719.
Mindy Hung is an associate editor at Medscape.
MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Send press releases and comments to email@example.com.
MedscapeWire 2001. © 2001 Medscape Portals, Inc
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