As an opioid epidemic ravages the country — killing a staggering 60,000 people by overdose last year1 — a cutting-edge question on the frontier of neuroscience is: Can addiction be blocked in the brain? Even if it could, the question for IRBs will immediately be: Can an addict give informed consent?

To help answer these questions and inform this forward-thinking premise, researchers at Stanford University School of Medicine in California will use a recently awarded National Institutes of Health (NIH) grant as part of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. Led by principal investigator Laura Roberts, PhD, the team will work with IRB members, neuroethicists, and research subjects to develop informed consent tools for the addicted and the mentally ill.

The research questions include, “What are IRB members seeing in protocols that are coming to them?” says Roberts, a professor in the department of psychiatry and behavioral sciences at Stanford. “What are they worried about? How do they appreciate the different risks and the benefits? What concerns do they have about the technology? It’s very exciting to try to put together all these different perspectives and try to paint a picture of ethical issues in highly innovative neuroscience.”

As the science advances, questions of ethical research and informed consent arise in part because neurological interventions could theoretically alter concepts of identity and sense of self in research subjects. The NIH BRAIN initiative was started in 2013 to address such questions, and the following are some of the other research protocols recently receiving grants:

• Neurotics of deep brain stimulation (DBS) systems targeting neuropsychiatric and movement disorders. PI: Gabriel Lazaro-Munoz, PhD, Baylor Medicine, Houston.

• Ethics of patients and care partners perspectives on personality change in Parkinson’s disease and DBS. PI: Cynthia Kubu, PhD. Cleveland Clinic.

• Achieving ethical integration in the development of novel neurotechnologies. PI: Winston Chiong, MD, PhD, University of California, San Francisco.

• Ethical safeguards for exit and withdrawal from implanted neurotechnology research. PI: Lauren Sankary, JD, Cleveland Clinic.

Q&A

For her part, Roberts also will examine how those with addiction or mental illness as compared to a healthy control group decide whether to participate in neuroscience research studies. Roberts fielded questions from IRB Advisor about the research.

IRB Advisor: Can you tell us a little about your background that led to this research project?

Roberts: I’ve been doing evidence-based ethics research for many years now. A big focus has been considering the perspectives of the people who have to “live out” the research. That might be the participants, the investigators, and the institutional review boards charged with the oversight. I make sure to take into consideration the responsibilities and perspectives of the different stakeholders in the work. I have done studies of people involving HIV, cancer, and schizophrenia, looking at questions like, “Do people view mental illness as different than physical conditions when it comes to the research context and vulnerability?”

In addition, I’m looking at the research context when it comes to IRB members. Some of our work has studied how IRB members assess risk, and how that might compare with how a person with illness, or an investigator, views risk.

IRB Advisor: This recently grant-funded study will follow similar lines?

Roberts: This new project, especially the initial phase, is very faithful to that kind of approach. We are trying to look at highly innovative brain research — neuroscience that, in particular, relates to mental health and addiction conditions. We don’t have separate federal regulations [for them], so people are often concerned about vulnerability and exploitation in the research context. In the initiation phase of this study, we are talking with IRB members, innovative neuroscientists, and ethicists. We are also talking with people living with either a mental disorder or an addiction, or people who are family members of those with these conditions. We are trying to get a full set of concerns, impressions, and observations about what is going on in highly innovative neuroscience research. Whether it’s studying circuits on stem cells — that is what we are going to learn. What are investigators actually encountering from an ethical point of view when they are trying to develop this really forward-thinking science? That is the first phase.

IRB Advisor: Where will it go from there?

Roberts: Based on that, we are going to do a fairly broad survey that will include people with mental illness and addiction, and healthy comparison subjects. We will look at their motivations for going into research, exploring sources of strength or vulnerabilities that would bring them to potentially signing up for highly innovative brain research. We are not going to actually develop the [consent] tool in this particular project, but our goal is to develop a more nuanced method or approach that scientists could use to look at what motivates a person to come to a research project. If they are just desperate, or they can’t get access to healthcare any other way, or they are pressured into it, then this tool or this method that we hope to develop in the next [phase] of this project would help to understand that. I think from an IRB point of view it could be a wonderful safeguard to adopt to help evaluate the authenticity of the consent and the ethical suitability of the participation by the research subjects.

IRB Advisor: How will the research component specifically looking at IRBs be set up in this first phase?

Roberts: Right now, we are going to use semi-structured, confidential interviews just to create a deeper understanding of the kinds of ethical issues that are coming up. That will help build this big survey we are going to do. I have also been talking with the NIH about whether we could do a much broader survey — a written or web-based survey. We are going to start with the Stanford IRB. At this stage, we are just using the information to develop the survey instruments, so we are keeping it kind of small but in a highly advanced setting.

I just did a big project with IRB members nationally that looked at whether genetic research for psychiatric conditions was viewed in a special or different way across the country. We just finished that and we are starting to write up the data. It has not yet been published. We did deep engagement of IRB members across the country for that particular project.

IRB Advisor: Addiction certainly is a timely topic. Will there be separate research and possibly tools developed for addiction?

Roberts: I have been working in the addiction space for about 20 years. I can tell you on theoretical grounds that I believe we are going to have to build tailored instruments for working with addiction, because part of the definition of having an addiction is some sense of loss of control. To have informed consent, you have to obviously have adequate information and dialogue, and then decisional capacity. Authentic volunteerism is really a challenge when people feel powerless [due to] an addiction. Also in some mental illness as well, the nature of the symptoms themselves render the person feeling powerless or helpless — unable to read their own internal state. Those are all really threats to volunteerism.

IRB Advisor: What kind of neurology research breakthroughs might be possible for these vulnerable groups?

Roberts: That is a lot of what we are going to learn, but [some examples include] the brain-computer interface, artificial intelligence, and simulations that represent decision-making in vulnerable people. [The research could involve] taking stem cells and growing neurons from a particular person in vitro, then creating circuits with those neurons. There are a lot of really interesting ethical questions that come up.

IRB Advisor: Do you think it might be possible to alter brain neurology in a way to blunt addiction?

Roberts: We hope so, by understanding the circuits that govern motivation, craving, and impulses. If we could do some kind of intervention on those circuits, then we may be able to diminish the power of the addiction. The ethical challenge then is preserving all of the dimensions that make an individual person who they are. We don’t want to be changing people or changing humanity fundamentally, but we do want to address these conditions that render people less than themselves. There are a lot of challenges here.

REFERENCE

1. Centers for Disease Control and Prevention. O’Donnell JK, Halpin J, Mattson CL, et al. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July-December 2016. MMWR. ePub: 27 October 2017. Available at: http://bit.ly/2idBfPT. Accessed Nov. 6, 2017.