Ethical Challenges of Risk, Informed Consent, and Posttrial Responsibilities in Human Research With Neural Devices
Review
Saskia Hendriks, Christine Grady,  Khara M. Ramos, Winston Chiong, Joseph J. Fins, Paul Ford, Sara Goering, Henry T. Greely, Katrina Hutchison, Michael L. Kelly, Scott Y. H. Kim, Eran Klein, Sarah H. Lisanby, Helen Mayberg, Hannah Maslen, Franklin G. Miller, Karen Rommelfanger, Sameer A. Sheth, Anna Wexler
JAMA Neurology, 17 October 2019
Abstract
Importance  
Developing more and better diagnostic and therapeutic tools for central nervous system disorders is an ethical imperative. Human research with neural devices is important to this effort and a critical focus of the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Despite regulations and standard practices for conducting ethical research, researchers and others seek more guidance on how to ethically conduct neural device studies. This article draws on, reviews, specifies, and interprets existing ethical frameworks, literature, and subject matter expertise to address 3 specific ethical challenges in neural devices research: analysis of risk, informed consent, and posttrial responsibilities to research participants.
Observations  
Research with humans proceeds after careful assessment of the risks and benefits. In assessing whether risks are justified by potential benefits in both invasive and noninvasive neural device research, the following categories of potential risks should be considered: those related to surgery, hardware, stimulation, research itself, privacy and security, and financial burdens. All 3 of the standard pillars of informed consent—disclosure, capacity, and voluntariness—raise challenges in neural device research. Among these challenges are the need to plan for appropriate disclosure of information about atypical and emerging risks of neural devices, a structured evaluation of capacity when that is in doubt, and preventing patients from feeling unduly pressured to participate. Researchers and funders should anticipate participants’ posttrial needs linked to study participation and take reasonable steps to facilitate continued access to neural devices that benefit participants. Possible mechanisms for doing so are explored here. Depending on the study, researchers and funders may have further posttrial responsibilities.
Conclusions and Relevance  
This ethical analysis and points to consider may assist researchers, institutional review boards, funders, and others engaged in human neural device research.

Enhancing the Informed Consent Process Using Shared Decision Making and Consent Refusal Data from the CLEAR III Trial
Amanda L. Porter, James Ebot, Karen Lane, Lesia H. Mooney, Amy M. Lannen, Eugene M. Richie, Rachel Dlugash, Steve Mayo, Thomas G. Brott, Wendy Ziai, William D. Freeman, Daniel F. Hanley
Neurocritical Care, 30 September 2019; pp 1–8
Abstract
Background
The process of informed consent in National Institutes of Health randomized, placebo-controlled trials is poorly studied. There are several issues regarding informed consent in emergency neurologic trials, including a shared decision-making process with the patient or a legally authorized representative about overall risks, benefits, and alternative treatments.
Methods
To evaluate the informed consent process, we collected best and worst informed consent practice information from a National Institutes of Health trial and used this in medical simulation videos to educate investigators at multiple sites to improve the consent process. Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) (clinicaltrials.gov, NCT00784134) studied the effect of intraventricular alteplase (n = 251) versus saline (placebo) injections (n = 249) for intraventricular hemorrhage reduction. Reasons for ineligibility (including refusing to consent) for all screen failures were analyzed. The broadcasted presentation outlined best practices for doctor–patient interactions during the consenting process, as well as anecdotal, study-specific reasons for consent refusal. Best and worst consent elements were then incorporated into a simulation video to enhance the informed consent process. This video was disseminated to trial sites as a webinar around the midpoint of the trial to improve the consent process. Pre- and post-intervention consent refusals were compared.
Results
During the trial, 10,538 patients were screened for eligibility, of which only three were excluded due to trial timing. Pre-intervention, 77 of 5686 (1.40%) screen eligible patients or their proxies refused consent. Post-intervention, 55 of 4849 (1.10%) refused consent, which was not significantly different from pre-intervention (P = 0.312). The incidence of screen failures was significantly lower post-intervention (P = 0.006), possibly due to several factors for patient exclusion.
Conclusion
The informed consent process for prospective randomized trials may be enhanced by studying and refining best practices based on trial-specific plans and patient concerns particular to a study.