Of Monkeys and Men: Analysis of the Phase 2 Double-Blind, Sham-Surgery Controlled, Randomized Trial of AAV2-Neurturin Gene Therapy 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?

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Preladenant in patients with Parkinson's disease and motor fluctuations: a phase 2, double-blind, randomised trial

The Lancet Neurology ◽

10.1016/s1474-4422(11)70012-6 ◽

2011 ◽

Vol 10 (3) ◽

pp. 221-229 ◽

Cited By ~ 133

Author(s):

Robert A Hauser ◽

Marc Cantillon ◽

Emmanuelle Pourcher ◽

Federico Micheli ◽

Vincent Mok ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomised Trial ◽

Motor Fluctuations ◽

Phase 2 ◽

Double Blind

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The Placebo Response in Double-Blind Randomised Trials Evaluating Regenerative Therapies for Parkinson’s Disease: A Systematic Review and Meta-Analysis

Journal of Parkinson s Disease ◽

10.3233/jpd-212610 ◽

2022 ◽

pp. 1-13

Author(s):

Stephen Polgar ◽

Melissa Buultjens ◽

Tissa Wijeratne ◽

David I. Finkelstein ◽

Sheeza Mohamed ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Placebo Response ◽

Major Influence ◽

Moderate Degree ◽

Randomised Trials ◽

Double Blind ◽

Motor Functioning ◽

Sham Surgery ◽

Regenerative Therapies

In the field of stem cell technologies, exciting advances are taking place leading to translational research to develop cell-based therapies which may replace dopamine releasing neurons lost in patients with Parkinson’s disease (PD). A major influence on trial design has been the assumption that the use of sham operated comparator groups is required in the implementation of randomised double-blind trials to evaluate the placebo response and effects associated with the surgical implantation of cells. The aim of the present review is to identify the improvements in motor functioning and striatal dopamine release in patients with PD who have undergone sham surgery. Of the nine published trials, there was at the designated endpoints, a pooled average improvement of 4.3 units, with 95% confidence interval of 3.1 to 5.6 on the motor subscale of the Unified Parkinson’s Disease Scale in the ‘OFF’ state. This effect size indicates a moderate degree of improvement in the motor functioning of the patients in the sham surgical arms of the trials. Four of the nine trials reported the results of 18 F-fluorodopa PET scans, indicating no improvements of dopaminergic nigrostriatal neurones following sham surgery. Therefore, while the initial randomised trials relying on the use of sham operated controls were justified on methodological grounds, we suggest that the analysis of the evidence generated by the completed and published trials indicates that placebo controlled trials are not necessary to advance and evaluate the safety and efficacy of emerging regenerative therapies for PD.

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