In this issue of the Journal of Law, Medicine & Ethics Peter Clark provides a comprehensive and sound ethical analysis of clinical trials examining the treatment of advanced Parkinson's disease with fetal tissue transplantation. These studies raise profound questions about how clinical trials of surgical interventions ought to be conducted. At stake is not only the ethical basis of such trials, but differing views as to the proper role of science in medicine and its limitations.Experience with the broader debate on (...) the ethical permissibility of placebo controls has taught us that the choice of control treatment is an aspect of trial design in which ethical and scientific issues overlap. Accordingly, I will highlight, and perhaps expand upon, three issues raised by Clark: What scientific questions ought clinical trials of surgical interventions ask? How should the ethical analysis of risk for such trials be conceived? And, are surgical patients a vulnerable population? (shrink)

For a few decades, patients with Parkinson's disease have been treated with intracerebral transplantations of fetal mesencephalic tissue. The results of open trials have been variable. Double blind, placebo-controlled studies have recently been started in order to further investigate the efficacy of this new medical technique. In this paper we challenge the need for sham surgery in neurotransplantation research on PD patients. Considerations regarding the research subjects' informed consent, therapeutic misconception, the integrity of the human body, and the assessment of (...) risks and benefits argue against sham surgery for patients with PD. Moreover, there is an alternative, less harmful mode of research that can provide the same or comparable scientific evidence. A plea is made for intrapatient research based on quantitative measurements of the patient's pre- and post-operative condition combined with similar research on a reference group of patients who have received the standard treatment. (shrink)

Sham surgery is a controversial and rarely used component of randomised clinical trials evaluating surgical interventions. The recent use of sham surgery in trials evaluating efficacy of intracerebral fetal tissue grafts in Parkinson’s disease has highlighted the ethical concerns associated with sham surgery controls. Macklin, and Dekkers and Boer argue vigorously against use of sham surgery controls. Macklin presents a broad argument against sham surgery controls while Dekkers and Boer present a narrower argument that sham surgery is unnecessary in the (...) specific setting of fetal tissue engraftment for Parkinson’s disease. I defend sham surgery controls against both these criticisms. Appropriate clinical trial design, sometimes including sham surgery, is needed to ensure that false positive trial results do not occur and endanger public safety. Results of a completed trial of fetal tissue grafting for Parkinson’s disease are used to illustrate the potential benefits of, and problems associated with, sham surgery controls. Sham surgery controls, however, should be employed only when absolutely necessary. I suggest criteria for appropriate use of sham surgery controls. (shrink)

The leading ethical position on placebo-controlled clinical trials is that whenever proven effective treatment exists for a given condition, it is unethical to test a new treatment for that condition against placebo. Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit. We contend that both of these arguments are mistaken. (...) Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials, because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials. Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm. (shrink)

In April 1999, Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in New York presented the results of a four-year, $5.7 million government-financed study using tissue from aborted fetuses to treat Parkinson’s disease at a conference of the American Academy of Neurology. The results of the first government-financed, placebo-controlled clinical study using fetal tissue showed that the symptoms of some Parkinson’s patients had been relieved. This research study involved forty subjects, (...) nineteen women and twenty-one men; all suffered from Parkinson’s disease for an average of 13.5 years. In the study, each subject underwent neurosurgery: “four tiny burr holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of fetal cells into the putamen, the region of the brain that controls movement; the other half received nothing. One year later, three members of the placebo group said their symptoms had improved.” In two-thirds of the transplant recipients, the fetal tissue took hold and seemed to establish a new network to produce the missing neurochemical dopamine. (shrink)

Recent debates over the use of sham surgery as a control for studies of fetal tissue transplantation for Parkinson’s disease have focused primarily on rival interpretations of the US federal regulations governing human-subjects research. Using the core ethical and methodological considerations that underwrite the equipoise requirement, we nd strong prima facie reasons against using sham surgery as a control in studies of cellular-based therapies for Parkinson’s disease and more broadly in clinical research. Additionally, we believe that these reasons can be (...) generalized to apply to the use of other placebo controls that carry signi cant risks of positive harms in and of themselves. As a result, our arguments are centrally relevant to the emerging drive to subject therapies with a surgical component to the same rigorous standards of evaluation as those governing the approval of new pharmaceuticals. (shrink)