Abstract:

Translation of recent advances in stem cell research into clinical trials for restorative therapies for human disease is dramatically accelerating. There is a strong focus upon neurodegenerative disorders such as Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). In particular, first-in-human intracerebral transplantation of cells derived from human embryonic stem cells (hESC) and inducible pluripotent cells (iPS) is likely within the next few years and intraspinal transplantation of hESC-derived cells has been recently reported in ALS. As clinical trials are planned and implemented, it will be critical to attend to the ethical framework necessary for responsible translation of scientifically compelling, but risky, interventions in humans. In particular, these clinical trials will present a variety of challenges to the informed consent process. We therefore review barriers to obtaining a truly informed consent in early phase stem cell clinical trials in neurodegenerative conditions, and examine procedures and interventions that have been investigated to potentially address and overcome these barriers. A variety of neurodegenerative disorders are thought to be amenable to restorative therapies using stem cell-based interventions. However, many studies raise concerns that “standard” consent processes may be insufficient to ensure that potential study participants’ decisions to enroll in such trials are indeed autonomous and made voluntarily, based upon their understanding of adequately disclosed information about the trial. Although some of these concerns are common to all trials, the important uncertainty regarding the risks and potential benefits of stem cell trials in neurodegeneration makes the need for development of guidelines for researchers imperative. We suggest that conveying complex and nuanced scientific information and reducing the effects of the therapeutic misconception could be addressed by extended consent procedures that might take place over time, and that can incorporate tablet-based or web-based materials. Researchers will need support in the use of expanded consent processes that may involve multiple media. The recognized need for long term follow up also necessitates changes in how capacity is assessed over time, and how to address a situation in which a subject loses capacity, for example due to progressive cognitive decline associated with some neurodegenerative disorders. As the field as a whole works towards consensus, we recommend close collaborations, not only between preclinical and clinical research teams, but also with bioethicists and individuals (usually psychiatrists) skilled in assessing capacity, and local IRBs familiar with issues particular to a given geographic region or culture.