Ethics Review Urges Changes to Deep Brain Stimulation Trials for Alzheimer’s Disease

Trials of deep brain stimulation for Alzheimer’s disease bring with them unique ethical challenges that need to be addressed because these studies are progressing, researchers argue in a recent review article.

The trio behind the review — researchers from the University of Pennsylvania — not only raised points for concern, but also provided potential solutions to issues dealing with decision-making in Alzheimer’s patients and post-trial access to treatment.

In this way, the ethics review, “Deep Brain Stimulation for Alzheimer’s Disease: Ethical Challenges for Clinical Research,” laid out guidelines for researchers who are considering starting trials of deep brain stimulation in Alzheimer’s patients. The article was published in the Journal of Alzheimer’s Disease.

“As the number of people affected by Alzheimer’s continues to grow, along with its substantial costs to individuals, their families, and society, novel therapies are urgently needed,” Andrew M. Siegel, MD, a study author and an assistant professor of Clinical Psychiatry at the Perelman School of Medicine at Penn, said in a press release.

“Deep brain stimulation is one such treatment modality that has shown promising early results. However, this enthusiasm should be tempered by prudent ethical considerations to help better protect the patients,” he said.

Although more well-known in the context of Parkinson’s disease treatment, deep brain stimulation may be used for various movement and neuropsychiatric disorders. The method includes surgically implanting a probe and a stimulator device that sends electrical impulses to the brain.

Early trials in Alzheimer’s disease have shown promising results, but the researchers claim that there are three main ethical problems surrounding such trials.

The first relates to the decision-making capacity of patients. Because of the inherent cognitive limitations of Alzheimer’s disease, the capacity of patients to provide informed consent is greatly reduced. Informed consent is a cornerstone of clinical trials, and a patient should have the right to opt out of a trial at any stage.

The Penn researchers suggested that trials need to have strong mechanisms in place to detect decision capacity loss. Such a framework would also protect the patient’s interests during a trial.

The researchers — also including Marna S. Barrett, PhD, an adjunct associate professor of Psychology, and Mahendra T. Bhati, MD, a former assistant professor of Clinical Psychiatry at Penn, who is now at Stanford University — suggested that assessments of decision-making capacity could solve the issue.

Alternatively, a person not associated with the study could be asked to determine how much a patient understands about the procedures and risks involved.

The second issue that concerns therapeutic misconception. With this, the researchers mean that patients who are desperate for a treatment may agree to a trial in the belief that a trial’s main aim is to provide health benefits, and not to study the effectiveness of a device or approach.

“It may be necessary to directly inform patients during study consent that scientific goals will have priority over therapeutic goals,” the authors said in the review, and suggested that it may be beneficial to have a waiting period, during which a patient can consider the option.

Finally, they raised the question of access to treatment after a trial. Deep brain stimulation is a costly procedure, so the access issue raises the question of who will pay for post-study continued treatment.

In the researchers’ view, it would be unethical to remove a device that works. Different parties — including sponsors, investigators, healthcare systems, insurance, governments, non-profit organizations, and the patients themselves — need to work together to share the responsibility. Such agreements must be in place before a patient joins a study, the authors point out.

“Providing post-trial access to the subset of patients shown to benefit in a failed trial is not only ethically appropriate, but it would allow for the collection of longitudinal safety and efficacy data not captured in the original study,” Siegel said.

“We hope this review facilitates the development of study designs and Institutional Review Board oversight procedures that best protect research subjects,” he added. “A reasonable next step is for research centers and hospitals to examine their current practice and policies guiding deep brain stimulation in Alzheimer’s research. Our review could act as a guide in helping them ask the relevant questions about their current state of oversight and to consider changes as appropriate.”