Stephen Polgar, Leila Karimi and Meg E. Morris
Randomized controlled trials [RCTs] are recognized as the most rigorous method for evaluating the safety and efficacy of novel interventions. The fact that a series of RCTs evaluating cellular therapies for Parkinson’s disease [PD] resulted in negative outcomes has delayed the translation of stem cell research into viable treatments for people with brain damage. At present, there are a variety of strategies being followed to improve outcomes for cellular therapies, including reassessment of the theory and methodology guiding the research program. In this position paper we present an argument based on empirical and theoretical grounds that the use of double-blind, placebo controlled trials are not the best approach for testing the efficacy of cellular therapies for PD. Evidence includes the highly variable effects of neural grafts found in double blind RCTs in comparison to the much larger benefits in open-label trials for people with PD in double-blind RCT. We suggest that the ambiguity and confusion created about the actual nature of the treatment in the context of a double-blind trial compromises the efforts of participants and their Carers to make the best therapeutic use of the grafted cells. The theoretical grounds for rejecting the use of double-bind RCTs is based on the Composite Brain Theory, which postulates that to insure optimal therapeutic outcomes it is essential to integrate the intracerebral grafting of cells with an active program of neurorehabilitation. We are recommending the use of pragmatic RCTs which involve the comparison of cellular transplantation and rehabilitation with best practice pharmacotherapy or Deep Brain Stimulation as comparison groups. Using a pragmatic trial design will ensure optimal outcomes for each of the treatment groups and produce evidence applicable for identifying best available treatments for people with PD.
