Overcoming Methodological Challenges for Advancing Stem Cell Therapies in Parkinson's Disease.

The quest for new and improved therapies for Parkinson's disease (PD) remains of paramount importance, despite previous trial failures. There is a current debate regarding the potential of stem cell research as a therapeutic approach for PD. The studies of dopaminergic fetal stem cells for PD treatment, their design, and the results of the initial surgical placebo-controlled trials were reviewed in this study.

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

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.

Evidence-Based Evaluation of the Ethics of Sham Surgery for Parkinson's Disease.

The stated purpose of sham or placebo surgery is to enable the implementation of surgical placebo-controlled trials (SPTs) for evaluating the safety and efficacy of surgical interventions. Exposing the participants to the burdens and harms of sham surgery has been justified on the grounds of the absolute necessity for controlling large placebo effects and observer bias, assumed to be associated with surgical procedures. In the present review, we argue that evidence obtained from SPTs of cellular therapies for the treatment of Parkinson's disease (PD) has failed to demonstrate either large and consistent placebo effects or decisive methodological advantages for relying on sham surgical controls.

Assessing the Efficacy of Cell Transplantation for Parkinson's Disease: A Patient-Centered Approach.

Background: Evidence from a growing number of preclinical studies indicate that recently discovered stem cell lines may be translated into viable cellular therapies for people with Parkinson's disease.

Objectives: In a brief but critical review, we examine the use of primary and secondary outcome measures currently used to evaluate the efficacy of cellular therapies.

Methods: The current practice of relying on a single primary outcome measure does not appear to provide the evidence required for demonstrating the robust, life-changing recovery anticipated with the successful implementation of cellular therapies.

A Critical Evaluation of the Methodological Obstacles to Translating Cell-Based Research Into an Effective Treatment for People With Parkinson's Disease.

The remarkable scientific and technological advances in the field of cell research have not been translated into viable restorative therapies for brain disorders. In this article, we examine the best available evidence for the clinical efficacy of reconstructive intracerebral transplantation in people with Parkinson's disease (PD), with the aim of identifying methodological obstacles to the translation process. The major stumbling block is the fact that the potential contributions of people with neural grafts and the effects of the physical and social environment in which they recover have not been adequately investigated and applied to advancing the clinical stages of the research program.

Composite brains: toward a systems theory of neural reconstruction.

The results of uncontrolled, open-label clinical trials indicate that reconstructive cellular therapies have the capacity to produce meaningful functional improvements in patients with brain disorders. However, the transplantation of fetal cells has not progressed to viable best practice treatment for any brain disorder. A conceptual approach, referred to as the Repair Model, has served as a useful heuristic for initiating research in the field and guiding the development of new practices.

A critical analysis of evidence for using sham surgery in Parkinson's disease: implications for public health.

Sham surgery was introduced as a means for improving the methodological quality of surgical research and evaluation. The development of cellular-based surgical therapies for the treatment of Parkinson's disease provides an opportunity to carefully analyse the alleged methodological benefits of sham surgery. However, detailed analysis of the evidence does not support these hypothesised advantages.

Ethics, methodology and the use of placebo controls in surgical trials.

There is an emergent view among North American researchers and bioethicists that not only is the use of sham surgery ethical, but that it should also be mandatory when conducting trials to evaluate surgical procedures such as neural grafting. This view is based on erroneous assumptions concerning the magnitude of the placebo effects associated with surgery. A detailed analysis of four recent clinical trials failed to provide consistent evidence for pronounced and long term improvements in sham operated patients.