Sham neurosurgical procedures in clinical trials for neurodegenerative diseases: scientific and ethical considerations.
There have been several recent scientific advances in gene-based and cell-based therapies that might translate into novel therapeutic approaches for neurodegenerative disorders. Such therapies might need to be directly delivered into the CNS, and complex scientific and ethical assessment will be needed to determine whether a sham neurosurgical arm should be included in clinical trials assessing these agents. We have developed a framework of points for investigators to consider when designing trials that involve direct delivery of a therapeutic agent to the CNS. The inclusion of a sham neurosurgical arm will be guided in part by the objectives of the clinical study (preliminary safety, optimisation, and feasibility vs preliminary efficacy vs confirmatory efficacy) and the need to minimise bias and confounds. Throughout the clinical development process, the perspectives of researchers, ethicists, and patients must be considered, and risks should be minimised whenever possible in a manner that is consistent with good trial design.
Office of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd, #2225, Bethesda, MD 20892, USA. galpernw@ninds.nih.gov
Wendy R
WR
Galpern
Jacqueline
J
Corrigan-Curay
Anthony E
AE
Lang
Jeffrey
J
Kahn
Danilo
D
Tagle
Roger A
RA
Barker
Thomas B
TB
Freeman
Christopher G
CG
Goetz
Karl
K
Kieburtz
Scott Y H
SY
Kim
Steven
S
Piantadosi
Amy
A
Comstock Rick
Howard J
HJ
Federoff
D002986:Clinical Trials as Topic / Q000941:ethics*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000628:therapy*; D019635:Neurosurgical Procedures / Q000941:ethics*; D033281:Nontherapeutic Human Experimentation / Q000941:ethics*; D010919:Placebos
D010919:Placebos