||The randomized, placebo-controlled clinical trial is generally viewed as the gold-standard in clinical investigation. However, when a trial involves a sham surgical procedure, unique scientific and ethical issues emerge. There are several examples of positive findings in open label studies of cell or gene therapies in Parkinson’s disease where subsequent trials which included a sham neurosurgical arm failed to show a difference between treatment arms. While sham neurosurgical arms have often been included in recent gene therapy trials for Parkinson’s disease (four of six that have been initiated since 2003) and Alzheimer’s disease (one trial started enrolling in November of 2008), their use is not without controversy.
As novel therapies are developed for neurodegenerative diseases, questions will arise about whether to include a sham arm and, if so, at what stage in development. Institutional Review Boards and patients will face complex decisions regarding such studies.
The NIH Office of Biotechnology Activities, Office of the Director and the National Institute of Neurological Disorders and Stroke have developed this conference to explore the scientific and ethical issues regarding sham neurosurgical arms and to provide a foundation for the development of points to consider when designing clinical trials which involve delivery to the central nervous system. The specific goals are to:
Increase our understanding of the utility and limitations of sham neurosurgical procedures through a review of the prior clinical trial experience in Parkinson’s disease
Address how experiences from trials in Parkinson’s disease may inform clinical trial design for other neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and Huntington’s disease
Discuss the scientific and ethical issues raised by the use of sham neurosurgical procedures, including trial design, subject recruitment, risk assessment, and informed consent
Explore the perspective of patients regarding the design of trials that may involve sham neurosurgical procedures