Brain devices: Navigating collaborations between industry, government, and researchers

by Paul J. Ford, PhD



Dr. Ford is Director of the NeuroEthics Program at the Cleveland Clinic. He is an active clinical ethicist, and teaches ethics to medical students, residents, and fellows. His publications have appeared in Science, The Hastings Center Report, Neurology, Neuromodulation, and Journal of Medical Ethics. He is also a board member for AJOB Neuroscience.



This spring (June 3-4, 2015) the National Institutes of Health (NIH) as part of the BRAIN Initiative convened an eclectic group of individuals in hopes of encouraging more investigator initiated studies of currently approved neuromodulation and neuro recording devices for new indications (agenda, session videos, and program goals available here). The participants, both on the program and in the audience, specifically included industry, researchers, universities, and governmental agencies. I was delighted to participate in the workshop and was impressed by the number of sincerely interested parties across the spectrum of roles. Within these conversations it was apparent that there existed many shared values and goals as well as complex challenges for protecting particular interests. It beautifully highlighted the complexities of interactions among varied stakeholders.





Among the group there was a broad interest in performing due diligence in discharging their various duties to their constituents. At its heart, the meeting was a good faith effort to realize a desire to see innovations develop to the point of helping clinical populations, i.e. real people who suffer. This aspect of the BRAIN initiative recognizes the current significant logistical barriers to exploring new uses of existing devices within a research context. Too often the current system in the United States with respect to devices encourages off-label use with retrospective review data, rather than small prospective trials. There are numerous disincentives within the system, some of which are bureaucratic and legalistic in nature (see Kelly et al. discussion.) In developing new ways for investigators to create partnerships with industry, the June meeting announced opportunities that would allow easier access to letters for “right of reference” (a specific type of permission needed from intellectual property owners to allow use of previously submitted safety and engineering data. Kelly et al. discusses this further) as well as standardized intellectual property agreements as part of a streamline for some types of NIH funded research. In addition, the dialogue between industry, researchers, universities, regulators, and funders creates an opportunity to standardize approaches to some of the most difficult ethics challenges in brain implant research, such as long-term access to implant upgrades.



Much of the June meeting itself was dedicated to understanding the mechanisms for collaboration, addressing the challenges of negotiating intellectual property, as well as the need for further aggregation of data across research studies. However, the organizers also dedicated a session specifically to ethics, in which I participated as a panelist. The session included a brief presentation by Joseph Fins, MD followed by panel comments by Christine Grady, MSN, PhD, Scott Kim, MD, PhD, Helen Mayberg, MD, and me. A diverse set of practical ethical issues were addressed relating to both research ethics in general and specific ethical issues in neuromodulation. Scott Kim particularly highlighted the opportunity for neuroethics research that could be undertaken in parallel to the other science conducted during further neurological device studies. This model of integrating ethical investigation in tandem with the initial clinical research provides an opportunity to fully appreciate the research participants’ perspective.



A second session of particular interest to the neuroethics community was a presentation by a Public-Private enterprise, Medical Device Innovation Consortium (MDIC) developed in collaboration with the FDA. This organization “aims to advance regulatory science in the medical device industry.” In particular it has various industry, non-profit, and governmental members. This past spring, they released a report on a framework for use in demonstrating to the FDA whether a risk benefit balance is appropriate from a patient perspective (draft release May 2015). The FDA released a companion draft guideline regarding how patient preferences could be used in the approval process. These draft guidance documents provide an opportunity to include neuroethics research into clinical trials of neurological devices. Scott Kim’s comment regarding the need for rigorous methods to be applied in undertaking the type of ethics research nicely resonates with the intention of the MDIC document to provide guidance of methods.



The initiatives and conversations that occurred during this June 2015 meeting is well worth paying attention to for their long reaching implications on how neurological device research is approached and the ethics opportunities that are available.



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Ford, P.J (2015). Brain devices: Navigating collaborations between industry, government, and researchers. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2015/09/brain-devices-navigating-collaborations.html

Intellectual Property from Clinical Research on Neuropsychiatric Disorders: What Constitutes Informed Consent?

By Elaine F. Walker, Ph.D. & Arthur T. Ryan, M.A.





Elaine Walker is a Professor of Psychology and Neuroscience in the Department of Psychology at Emory University and is the Director of the Development and Mental Health Research Program, which is supported by the National Institute of Mental Health. Her research is focused on child and adolescent development and the brain changes that are associated with adolescence. She is also a member of the AJOB Neuroscience editorial board.



The pace of advances in biomedical research has accelerated in conjunction with new technologies for studying cellular processes. While this progress holds promise for relieving human suffering from a range of illnesses, it also poses significant and thorny questions about the ownership of new knowledge. In June of 2013, the Supreme Court issued a unanimous ruling on the Association for Molecular Pathology v Myriad Genetics, Inc.; all justices agreed that naturally occurring DNA sequences cannot be patented¹. This ruling was precipitated by a patent owned by Myriad genetics on the DNA sequences for the human BRCA1 and BRCA2 genes, which are associated with human variation in susceptibility to cancer. The ruling concluded that genes are products of nature and, therefore, cannot be claimed as the intellectual property (IP) of any individual or commercial entity. Within hours after this ruling, other companies announced that they would offer genetic testing for BRCA1 and BRCA2 at a significantly lower cost than Myriad had been charging for years.




While the Supreme Court's ruling on the patentability of naturally occurring human genetic sequences had broad and immediate implications, it represents only the tip of the iceberg with respect to the contentious issues that will confront intellectual property (IP) rights for future biomedical advances. We can anticipate more ethical and legal debates regarding commercialization in the fields of proteomics (the study of protein structure and function), epigenetics (changes in gene expression mediated by RNA, as opposed to changes in the DNA code), stem cells, and the study of the human connectome (the map of neural connections in the brain). The implications of the pursuit of patents in these areas will extend to all fields of medicine, but they present some particularly complex problems with regard to the brain disorders that are the province of neurology and psychiatry.




By way of background, most consent forms approved by institutional review boards (IRBs) do not explicitly inform prospective participants that IP may be generated using the biospecimens they provide during their participation. Some have argued that researchers are ethically obligated to inform participants that the investigator may benefit financially from the research, whereas the participant will not². On the other hand, it has been argued that individuals who are capable of providing informed consent would be expected to be aware that patents might be obtained on marketable biomedical products that result from scientific advances³.




Can the same assumptions be made for all prospective participants? Clinical research aimed at elucidating the causes and effective treatments for neuropsychiatric disorders are dependent on the participation of volunteers who are either at risk for, or diagnosed with, such a disorder. This includes studies of individuals at risk for psychotic and mood disorders, and dementia and other neurodegenerative illnesses. As a result, these research volunteers may be suffering from symptoms that impair their cognitive capacities. Such impairments have the potential to diminish their ability to comprehend the information provided during the consenting process, as well as their comprehension of the broader implications of their property rights to their biospecimens and the knowledge that might be generated with them⁴. Nonetheless, informed consent procedures are used with these clinical research populations, albeit with extra consideration given to assure their understanding of the procedures. Ruling out informed consent by individuals who may be suffering from, or at risk for, a brain disorder would severely compromise scientific progress on these illnesses. At the same time, the ethical complexities of patents on the IP generated by such research cannot be ignored.




Concerns about risk status are a motivator for many participants in clinical research. Most IRBs require that consent forms include a ‘disclaimer’ statement concerning the likely absence of direct benefit to the participant. Yet, it is not clear that most prospective participants, especially those at risk for neuropsychiatric disorders, are aware that they may not have access to any advances in risk prediction that accrue from the research in which they participate. Thus, if a diagnostic test that enhances risk prediction and/or informs effective treatment results from the research, participants may assume that their access to it is assured. Yet this may not be the case if the ‘discovery’ becomes IP and the investigator applies for a patent.




Several scenarios may ensue and these are unlikely to be anticipated by most participants. For example, the pursuit of a patent may delay the public disclosure of the research findings, and in the interim the individual may succumb to an illness that might have been prevented if the discovery had been more promptly revealed. Further, the cost of the patented diagnostic test may be prohibitive for the individual, despite the fact that the participant contributed biospecimens that were used for the test's development. While such concerns are not unique to neuropsychiatric research, the ethical concerns are amplified in the case of individuals with cognitive impairments.




If participants were informed, as is the case in some European nations, that the researchers may benefit financially from discoveries made using their biospecimens, would that affect their willingness to participate? Although we are not aware of any research directly addressing this question, the results of studies of the general population indicate that many would be disinclined to consent to research participation if they were so informed ^3,5.




It is clear that research advances in biomedical risk assessment, combined with trends toward commercialization, raise serious questions that are likely to become even more salient. Perhaps the most important question we must address is what information should be conveyed while obtaining the informed consent of prospective clinical research participants who provide biospecimens that might be used for commercial purposes. The ethical issues in this arena are especially noteworthy when the study population is characterized by limited cognitive capacity and when individual participants may be motivated by the desire for illness prevention or treatment access.






References




1. Ass’n for Molecular Pathology v. Myriad. Ct 133, 2107 (2013).



2. Godard, B., Schmidtke, J., Cassiman, J.-J. & Aymé, S. Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective. Eur. J. Hum. Genet. 11, S88–S122 (2003).



3. Steinsbekk, K. S., Ursin, L. Ø., Skolbekken, J.-A. & Solberg, B. We’re not in it for the money—lay people’s moral intuitions on commercial use of ‘their’biobank. Med. Health Care Philos. 16, 151–162 (2013).



4. Caplan, A. L. & Arp, R. Contemporary Debates in Bioethics. (John Wiley & Sons, 2013).



5. Sterckx, S., Cockbain, J., Howard, H., Huys, I. & Borry, P. ‘Trust is not something you can reclaim easily’: patenting in the field of direct-to-consumer genetic testing. Genet. Med. 15, 382–387 (2013).





Other Relevant Articles 



Andrews, L. B., & Paradise, J. (2005). Gene patents: the need for bioethics scrutiny and legal change. Yale J. Health Pol'y L. & Ethics, 5, 403.



DuBois, J. M., Beskow, L., Campbell, J., Dugosh, K., Festinger, D., Hartz, S., ... & Lidz, C. (2012). Restoring balance: a consensus statement on the protection of vulnerable research participants. American journal of public health, 102(12), 2220-2225.



Kim, S. Y., Caine, E. D., Currier, G. W., Leibovici, A., & Ryan, J. M. (2001). Assessing the competence of persons with Alzheimer’s disease in providing informed consent for participation in research. American Journal of Psychiatry, 158(5), 712-717.



Klein, R. D. (2013). AMP v Myriad: The Supreme Court Gives a Win to Personalized Medicine. The Journal of Molecular Diagnostics, 15(6), 731-732.



Rojahn, Susan Y. Cheaper Genetic Tests for Breast Cancer Risks in 2014? MIT Technology Review, December 31, 2013.






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Walker, E., Ryan, A. (2014). Intellectual Property from Clinical Research on Neuropsychiatric Disorders: What Constitutes Informed Consent? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/07/intellectual-property-from-clinical.html