Informed Consent and Sham Surgery as a Placebo in Fetal Cell Transplant Therapy Research for Parkinson’s Disease

Fetal cellular transplantation therapy research in Parkinson’s Disease has raised important ethical questions from its beginning. One of the most hotly debated aspects of the recent clinical research has been the use of sham surgery as a placebo for the control group. Ethicists and researchers have focused on the unique risk surgical placebos pose to research subjects as compared to conventional, medical placebos. This review will deal with informed consent and the use of use of sham surgery in the placebo arm of recent fetal tissue transplantation randomized, placebo controlled, double blind, clinical trials. Do current procedures for obtaining informed consent meet the challenge of adequately informing patients enrolling in experiments with significant risks not only in the experimental group but also in the placebo group?

Status of fetal tissue transplantation for the treatment of advanced Parkinson disease

In the first double-blind, placebo-controlled randomized study of fetal tissue transplantation for the treatment of patients with advanced Parkinson disease (PD), investigators found that implanted dopaminergic tissue can produce measurable improvement in young PD in the absence of medication (that is, the “off” state). The results of the study, however, also highlighted several serious limitations of transplantation. In the group of older patients in the study (in the typical age range of individuals afflicted with PD) no improvement was derived from the implant despite positron emission tomography–documented scan evidence that the graft survived and produced dopamine. Patients in the study were selected because they experienced motor fluctuations, and the transplant did not improve dyskinesias or the time required to remain “on” medication for any subgroup of patients, including young patients. Five of 33 implant-treated patients developed involuntary movements (dyskinesias or dystonia) that could not be eliminated by reducing antiparkinsonian medications. These included four patients with the best responses to transplantation. Finally, some sham-operated patients experienced a dramatic placebo effect lasting at least 1 year, which justified the controversial sham surgery. The authors believe that these problems must be solved before fetal tissue transplantation can be considered a therapeutic option for PD.

I Need a Placebo like I Need a Hole in the Head

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?