On November 3, 2014, the National Institutes of Health (NIH) convened a workshop entitled Ethical Issues in Neuroscience Research on the NIH Bethesda campus. The workshop brought together three dozen researchers, clinicians, bioethicists, and patient organization representatives, along with leadership from the National Science Foundation, the Food and Drug Administration, and NIH, to identify five to ten high priority areas for NIH-supported research that can inform policies pertaining to either the ethical conduct of neuroscience research or the ethical use of neuroscience research. Identified research priorities also should align with the NIH mission, be able to be addressed through data collection and analysis, and be either unique to neuroscience or have implications not previously explored through other disciplines.
To open the workshop, NIH Director Dr. Francis Collins emphasized the importance of integrating discussions of ethical issues throughout the research process, while NIH Deputy Director for Science, Outreach, and Policy Dr. Kathy Hudson described NIH’s ongoing efforts to address bioethical issues. Following these opening remarks were two roundtable discussions: Conducting Ethical Neuroscience Research and Adopting Neuroscience Research into Practice. To conclude the workshop, National Institute of Mental Health (NIMH) Director Dr. Tom Insel and National Institute of Neurological Disorders and Stroke (NINDS) Director Dr. Walter Koroshetz synthesized input from participants to develop the list of recommended high priority research areas.
Dr. Collins opened the workshop with a reminder that, as the current pace of neuroscience research continues to accelerate, building a solid ethical framework for the conduct of neuroscience research is a top priority for the NIH. Extending that framework to the application of neuroscience research and technologies will also be essential to ensure successful adoption of neuroscience discoveries by the medical community and the broader public. Dr. Collins added that as head of the Human Genome Project more than two decades ago, he faced similar concerns, both philosophical and practical, related to the ethics surrounding human genetics research. He stated that NIH needs to maintain a rigorous portfolio of research studies on ethical issues, the results of which will provide the empirical evidence necessary to ensure NIH maintains public trust and continues to advance groundbreaking research.
In her opening remarks, Dr. Hudson described President Obama’s tasking the Presidential Commission for the Study of Bioethical Issues with assessing neuroethical issues in light of the BRAIN Initiative in 2013. As part of his charge to the Commission, President Obama wrote, “In keeping with my Administration’s strong commitment to rigorous research ethics in all fields, I want to ensure that researchers maintain the highest ethical standards as the field of neuroscience continues to progress. As part of this commitment, we must ensure that neuroscientific investigational methods, technologies, and protocols are consistent with sound ethical principles and practices.”
Dr. Hudson discussed NIH’s portfolio of research addressing ethical issues related to biomedical research. She reported that agency-wide, NIH funds $50 million in bioethics research annually. Each Institute and Center at NIH runs their own targeted ethics portfolio and the NIH Clinical Center has its own department of bioethics. As a specific example, the National Human Genome Research Institute (NHGRI) has had its own bioethics program since 1990, the year the Human Genome Project launched. The program focuses on ELSI (Ethical, Legal, and Social Implications) in genomic research, including: ethical issues relating to the use of stored genetic samples; models of informed consent; the balance of broad data sharing, privacy, and autonomy; public opinions about genetics research; identifiability of genetic specimens and data; incidental findings; and ethical and social issues in carrier testing, prenatal testing, newborn screening, predictive testing, and direct-to-consumer testing of both children and adults.
Since 2010, the NIH Office of the Director (OD) has received $5 million per year to fund ethics research intended to inform policy. This research has included studies on patient consent, secondary use of biospecimens, and the subsequent use of research data. In 2014, NIH OD issued three awards for research on the use of central institutional review boards (IRBs) to oversee multi-site studies, to understand the process of selecting and evaluating a central IRB, and to characterize differences between local and central IRB review. Two additional awards were issued to study ethical approaches to the research use of clinical records and data.
In closing, Dr. Hudson asked participants to focus their discussion on development of a set of high impact priority areas related to neuroscience research, which NIH could focus on in the near-term and which would fit in this existing context of NIH-supported ethics research.
Session I: Conducting Ethical Neuroscience Research
Moderator: Steven Hyman, MD – Director, Stanley Center for Psychiatric Research, Broad Institute; and Harvard University Distinguished Service Professor of Stem Cell and Regenerative Biology
Over the past two decades, neuroscience research has grown tremendously in the utility and sophistication of its research studies and products. This rapid development requires that standards for the ethical conduct of neuroscience research be continually evaluated and updated as necessary. In this session, participants discussed ethical concerns related to implantable, therapeutic devices used to record or modulate neural activity; sharing of human clinical data; and obligations to patients involved in research studies.
The discussion surrounding neural devices raised a number of ethical issues that may be informed by empirical research and applied to neuroscience research more broadly:
- Data collection in research versus clinical contexts – The first and most discussed issue regarding neural devices was how to navigate the boundary between research and clinical care for the purposes of data collection. Workshop participants agreed that there is a growing need for neural device data to be collected and shared in order to inform clinical practice, and that these data would be most useful if collected in a research setting, but that collecting large amounts of information in this way is highly unlikely. Furthermore, participants noted that neural devices are used for a variety of conditions with different outcome measures, with this lack of overarching standards for outcome measures posing a significant challenge to research in this area. They discussed different possibilities for incentivizing the collection and sharing of neural device data in clinical settings to leverage for research purposes (e.g., developing a central clinical database in which to track patients’ responses to different stimulation sites, stimulation parameters, or surgical procedures). They also noted that current databases, such as the Human Genome Project, could serve as a model for neural device databases.
- Data sharing and ownership issues – Participants also discussed the sharing of human clinical data, highlighting broad agreement on the importance of utilizing it effectively to improve health, while noting various associated challenges. For example, widespread data sharing poses a challenge to patient/participant privacy; questions exist over data ownership; and investment is needed to develop standardized data formats, databases, and infrastructure in order to ensure efficient and usable shared data. It is unclear how NIH can best incentivize scientists and clinicians to share data beyond funding data repositories and grants preferentially to groups that agree to share data. There was additional discussion among participants regarding neural device ownership. For example, if there are unintended benefits, should the clinician or patient determine when/how the device should be used? Workshop participants also noted the need to consider intellectual property and litigation issues when working with neural devices in a research context.
- Obligations to research participants – The group discussed obligations to research participants, especially in regard to ancillary care and return of research results. Workshop participants discussed concerns including the long-term responsibility for the health and associated healthcare costs of study participants with implanted neural devices. Also, with technologies advancing to enable prediction of future disease risk, there was consensus on the importance of helping research subjects and patients understand the accuracy of such predictive technologies. On the other hand, participants noted that it is unclear how, when, and to whom early research results should be revealed.
- Unintended consequences of neural stimulation devices – There was discussion regarding potential off-target effects, whether negative (e.g. increased anger, irritability, compulsive behavior, or difficulties with attention and memory after stimulation) or positive (e.g. during deep brain stimulation for obesity, a patient experienced some relief of Alzheimer’s symptoms http://www.ncbi.nlm.nih.gov/pubmed/18232017, an observation that has now been spun into a phase I study http://www.ncbi.nlm.nih.gov/pubmed/20687206), and how to help IRBs consider these types of consequences when reviewing risk/benefit ratios for neural stimulation research.
- Informed Consent – Workshop participants discussed a number of issues surrounding informed consent for neural device research, including the capacity to consent (i.e., can/how can individuals with neurological and/or psychiatric conditions consent to research) and surrogate decision-making; and how to disclose unknown and/or unintended risks and benefits associated with device implantation and usage.
- Additional topics raised in Session I – These included protection for vulnerable populations (how to define “vulnerable,” how to ensure privacy and discrimination protections for research participants given that there is no law equivalent to the Genetic Information Nondiscrimination Act); ethical issues involved in sponsoring and conducting prediction/prevention research; issues associated with neuroenhancement, especially in developing brains of children and young adults; considerations of cultural differences in ethics of neural device research; how to address individuals with a condition who are “high functioning” and openly disagree with research/clinical priorities for treating that condition (i.e., the neurodiversity movement); how to develop appropriate definitions for “spectrum disorders,” which include many developmental and psychiatric conditions; and ethical issues associated with animal models, both in the sense that they can become “humanized” through the introduction of human genes or cells, and in the issues surrounding the translation of animal research findings into effective diagnostic and treatment tools for neuroscience conditions.
Session II: Adopting Neuroscience Research into Practice
Moderator: Hank Greely, JD – Director, Center for Law and the Biosciences; Professor (by courtesy) of Genetics, Stanford School of Medicine; Chair, Steering Committee of the Center for Biomedical Ethics; and Director, Stanford Program in Neuroscience and Society
Neuroscience research results and technologies stand to change at a fundamental level how we prevent, diagnose, and treat neurological and psychiatric diseases, as well as how we understand our behavior and ourselves. Successful adoption of new technologies and research findings will require the research and medical communities to proactively address the many ethical and social issues that result from the translation of neuroscience research into clinical care. This session focused on ethical concerns related to the prediction of neurological and psychiatric conditions; neural enhancement; coercive or involuntary treatments; translational pathways from research to treatments; and public understanding of neuroscience. Professor Greely framed the session by encouraging workshop discussants to focus on five areas where ethical issues in the application of neuroscience research or technologies may be informed by empirical research:
- Prediction/prodromal use of neuroscience research–
- Workshop participants discussed the ethics of using biomarkers, cybermarkers, or other behavioral methods to predict behaviors or traits that are considered to be socially problematic, but not necessarily personally detrimental (e.g., aggression). Discussions focused on the normative question of whether it is ethically acceptable to use these predictive methods to change a child’s biology or environment, or whether informing parents of such predictors may become a “self-fulfilling prophesy” in that it alters the parents behaviors towards their children. Additional questions considered included the ethical ramifications of predicting future illness in the absence of effective treatments, and whether there should be an age threshold for any predictive testing, especially for conditions for which there is no cure. Relatedly, there was discussion of how the research and clinical communities might provide social support to patients predicted to experience illness, such as addressing social stigmas associated with certain neurological conditions, especially early in life when the brain is still developing. Participants also discussed whether it is ethical to mine social media to predict violent acts.
- There was also continued discussion of how to increase protection for research participants, as different modalities of prediction carry different legal protections. For example if Alzheimer’s disease is predicted based on a patient’s genotype she is protected from insurance and employment discrimination by the Genetic Information Nondiscrimination Act, but if the prediction is based on neuroimaging diagnostics, no such protection exists. Different modalities also have different regulatory requirements: for example, the FDA has different regulatory requirements for neurodiagnostics that test for disorders such as Alzheimer’s disease, vs. those that test for general attention or memory function. The group discussed whether there should be protections in place for other methods of predicting neurological or psychiatric conditions.
- Neuroenhancement –
- Workshop participants discussed the difficulties in distinguishing between treatment and enhancement. Often, therapies used to treat neurological, cognitive, or psychiatric conditions can also be used for enhancement purposes. Additionally, products used for enhancement could have significant health consequences (e.g., short-term use could impact the brain in the long-term). Related to this were discussions of whether it would be beneficial to research concepts of “normal” in relation to different conditions (to set boundaries/thresholds for what is considered “well” versus “ill”) in order to decide whether a treatment is being used for treatment or enhancement purposes.
- Many participants said that, given the limited public funds available for biomedical research, NIH research dollars should be spent researching treatments for patients with severe and life-threatening disease, rather than on developing neural enhancers. Other participants suggested that whether or not NIH funds enhancement research, people will make and use such drugs and devices, leaving the research community obligated to understand neural enhancers and associated risks to ensure protection of public health.
- Finally, questions were raised about how to address the abuse potential of enhancers and whether they could be ethically used in clinical settings.
- Coercive treatment for neurological or psychiatric conditions –
- There was discussion among workshop participants about ethical issues inherent in mandating patient treatment in the interest of public health. For example, the group raised for discussion the ethics of mandating vaccines against addiction to enhance overall public health, with consideration of issues such as vaccine-associated side effects, and whether there is a difference between vaccinating against addiction vs. vaccinating against communicable diseases. One participant suggested that there is a difference between modifying behavior and modifying antibodies, given that the brain and associated behavior are fundamental to what makes us human.
- There was special focus among discussants on the question of treating children, with participants stating that longitudinal studies ought to include children, and warning against cognitive bias in reviewing studies involving children. Participants also discussed the use of prenatal or neonatal research as a political tool (e.g., using results from fetal neuroscience research to support pro-life abortion legislation).
- Translational pathways for neuroscience research –
- Much of this discussion focused on identifying issues for which evidence is sufficient to justify translating research findings into standard clinical care (i.e., covered by CMS). Specific issues were raised, including reimbursement for “disorders of consciousness,” especially with respect to continued care for the minimally conscious; and evidence where treatments have been very successful, but the numbers have been small.
- Participants also discussed how to effectively communicate updated information regarding disease treatment and understanding to patients. Is there a way to create the equivalent of industry’s marketing departments for publically-funded research? It is also important for researchers and funders to “keep their finger on the pulse” of public understanding and attitudes regarding neuroscience technologies, to best gauge the likelihood of success for different translational efforts.
- Communication of neuroscience research –
- Science literacy was a major topic of discussion. Participants suggested ways to improve scientific literacy in order to help citizens utilize research results in making informed healthcare decisions, including incorporating bioethics into broader STEM conversations; utilizing surveys to gauge public understanding of neuroscience (or science more broadly); enhancing the quality of media coverage of science and scientific advances, perhaps by offering science boot camps to journalists; and training scientists to better communicate with the media, in part by not oversimplifying complex scientific issues.
- There was some discussion regarding public understanding of relative risk. The public consumes information about the relative risks of genetic and lifestyle factors for developing specific diseases, but it is unclear how well people understand what risk levels really mean.
- Getting public perspectives on the “mind/body” problem may be important, as it has implications in both the clinical and research contexts and for a number of ethical issues (e.g., autonomy, personal responsibility).
Session III: Setting Priorities
Moderators: Dr. Walter Koroshetz and Dr. Tom Insel In the final session, Dr. Koroshetz and Dr. Insel summarized the discussions in the two previous sessions in order to help develop this list of high priority research areas (listed in no particular order):
- Ethics of prodromal and prevention research
- Best practices to obtain informed consent
- Communicating risk and probabilistic outcomes
- Predicting illness in the absence of effective treatment
- Stigma associated with particular neurological or psychiatric conditions
- Obtaining informed consent
- Capacity to consent in populations with cognitive or psychiatric conditions
- Communicating risks and benefits of off-target, potentially unknown treatment effects on personality, abilities, mood, etc., especially for treatments involving neurosurgical devices and procedures
- Informing best practices in neuroscience research
- Obligations to participants:
- How, when, and to whom to reveal early research results
- Defining and assessing risk
- Respect for neurodiversity
- Understanding disparities in research/technology access and outcomes
- Data collection, sharing, ownership, standardization, privacy
- Effective ethics:
- Models for teaching and improving sensitivity to ethical issues of neuroscientists
- IRB review of risk/benefit ratios for neural stimulation research
- Understanding current ethical issues to determine what is effective and eliminate ineffective practices before adding new ones
- Adopting research into practice
- Understand which strategies for adoption are most effective
- Need for policy research § Ethics of unregulated/unsupported commercial applications for neuroscience
- Building a ramp between science and the regulatory path
- The developing brain
- Sensitive windows of development and plasticity – are childhood and young adulthood optimal or vulnerable times to study the brain?
- Define autonomy during adolescence and “coercion” in research studies for this population.
- Public perceptions of neuroscience research
- Need for social science research on public understanding and perceptions of neuroscience research and technologies, and to understand how people make health decisions and participate in research
- Other important issues but less related to the NIH mission:
- Ethics surrounding the application of neuroscience research findings and technologies in training and education
- Ethics of unregulated commercial applications of neuroscience research findings and technologies for enhancement (as opposed to treatment of brain disorders)