Benefits vs. Risks: Neural Device Maintenance and Potential Abandonment

This article refers to:

Disentangling Function from Benefit: Participant Perspectives from an Early Feasibility Trial for a Novel Visual Cortical Prosthesis

The study by Levy et al. (2024) offers new insights into clinical trial participant experience when assessing a novel visual cortical prosthesis (VCP) during an early feasibility study (EFS). We applaud the incorporation of ethical research within the EFS to guide appropriate development of this and related types of technology. The study involves the Orion VCP, but the author’s findings mirror previous discussions of other bionic devices and visual prostheses, including optogenetics methods (Gilbert, Harris, and Kapsa 2014; Harris and Gilbert 2021b; Harris and Gilbert 2022). In particular, they articulate that the benefits derived from neurotechnology trials cannot be solely attributed to device functionality. They observed that users’ experiences could be classified into six themes: the irreducibility of benefits to mere device functionality, mixed expectations regarding short-term device performance and long-term technological advancements of visual prostheses, and a broad spectrum of risks, concerns, and fears associated with trial participation. Accordingly, Levy et al. suggest that function should be interpreted distinctly from benefits. Here, we emphasize that it is crucial to recognize that individuals receiving these types of neural implants are more than mere subjects of functionality measurements; they are active participants in the development and evaluation of neural technology. Levy et al.'s work significantly contributes to the ongoing discourse on whether the potential benefits accrued in experimental trials sufficiently justify the associated risks of participation.

Levy et al. discuss the concept of benefit and how this can differ from the functionality of the device. This in an extension of previous discussions around trial endpoints typically involving the measurement of certain clinical outcome assessments (COAs), however these quantitative measures may have limited impact on a patient’s quality of life (Gilbert, Harris, and Kapsa 2014; Harris et al. 2024). There can also be difficulties in comparing treatments and trials that use different or proprietary COAs or alternately are based on qualitative patient reported measurements. As a result, trials may not deliver sufficiently generalizable knowledge for future patients to determine the most appropriate intervention for their clinical needs. This may undermine the EFS participants’ reason for being involved in the study and invalidate their informed consent. Therefore, we call for trial endpoints and COAs to be standardized across treatments and sponsors, and for greater investigation of generalizable methods to measure participants’ benefit when assessing novel treatments for blindness. By referencing the discontinuation of Argus II, Levy et al. highlight the parallels between the vulnerabilities observed in VCPs and other medical device trials. While the altruistic benefits of participating in an EFS may surpass measurable functionality and efficacy, the critical ethical question remains: Do these potential benefits justify all associated risks, including those associated with device maintenance, obsolescence, and patient abandonment? This issue is central to the ongoing discussion about obligations to trial participants being used to assess neurotechnologies (Harris and Gilbert 2024; Okun et al. 2024; Bublitz and Gilbert 2023).

Clinical trials assessing VCPs, other bionic devices and some treatments for blindness fall into a category of high-risk, irreversible treatments (Harris and Gilbert 2024). These types of trials distinguish themselves by one or more of the following attributes: 1) they may pose long-term risks of serious harm to trial participants (potentially occurring after trial conclusion), 2) it may not be possible to assess safety through administration of sub-therapeutic doses, 3) treatments may require ongoing interventions (beyond trial conclusion) to maintain safety or efficacy, 4) the trial is of a long duration where participants may experience significant health, mental or lifestyle changes, 5) participants may be excluded from future therapeutic options, and 6) participation in the trial may require changes to a person’s treatment regimen, leading to permanent deterioration of their health status. In the case of VCPs, points 1 to 5 apply.

Many participants may enroll in an experimental high-risk, irreversible trial viewing them as their ‘last chance’ treatment opportunity. From an ethical perspective, the issue extends beyond the lack of access to treatment due to potential harms and the irreversibility of the intervention. The critical concern is not merely that patients lose the opportunity for alternative treatments, but rather that their participation in an experimental high-risk, irreversible trial may preclude them from accessing more effective treatments in the future (Gilbert et al. 2015). Levy et al reported that participants had issues with the devices appearance and design, they note that useability engineering and human factor engineering (UE/HFE) should be undertaken early in the design process. Given the irreversibility of the proposed treatment, we recommend that UE/HFE processes should be compulsory before undertaking any irreversible interventions on trial participants.

The risk of harm to the participant might be even greater when the implantable device targets a psychiatric condition, as removal could exacerbate severe adverse psychological effects (Gilbert, Harris, and Kidd 2021). This raises the question: does disentangling function from benefit imply that some benefits may justify certain long-term harms? This question necessitates a closer examination of specific types of harms induced by these benefits, which might not be evident during the initial trials.

PARTICIPANTS AS COMPONENTS: EXAMINING HARMS RESULTING FROM BENEFIT

Even if irreversible effects from a neurotechnology trial are functionally beneficial (e.g., gene therapy), within the safety-only context of a traditional Phase 1 clinical trial, it is challenging to justify the severe risk to participants if future irreversible harms occur, especially if they are flagged as linked to benefits rather than functionality. Prioritizing benefits over functionality, particularly at first-in-human stages, does not necessarily resolve or even map the known irreversible physical and psychological consequences of trial participation against the personal costs incurred by the participant and the clinical and scientific knowledge gained from the trial.

Specifically, when benefits inadvertently lead to harms associated with maintenance, obsolescence, and patient abandonment (Okun et al. 2024), the failure to properly maintain and monitor implanted technology is a significant yet underexplored neuroethical concern that warrants greater attention. Inadequate maintenance can lead to recidivistic and rebound symptoms, along with psychological effects, potentially imposing unforeseen burdens on both patients and caregivers (Gilbert and Lancelot 2021). Examining how improper maintenance amounts to the infringement of core bioethical and legal tenets, particularly the duty of care (e.g., negligence not meeting the standard of care) is critical, even in a context where benefits were gained.

It is crucial to recognize that any implanted device exists within a temporal trajectory, particularly one influenced by technological durability and obsolescence. The term ‘durability’ in neurotechnology refers to the length of time a neural device remains functional and effective, requiring minimal maintenance or repair over its useful life. This concept applies not only to individual devices but also to their later iterations and versions (Okun et al. 2024).

As newer and more sophisticated types of implantable devices become commercially available, older models of neurotechnology may face obsolescence or increased maintenance challenges (Okun et al. 2024). In this rapidly evolving landscape of implantable neurotechnologies, participants receiving these implants are more than just passive recipients or subjects of potential benefits. They are, in fact, active components and can be considered a form of infrastructure. They serve as the foundational structure that enables the functioning, utility and benefit of these novel neurotechnologies. For these reasons, we see potential benefits and harms affecting, first, the body as infrastructure and, as a site of maintenance, and secondly, as a process, extending the concept of durability. Testing experimental neural device under the cover of gaining benefit while neglecting maintenance and durability buys into wrongdoing.

The possibility of treatment obsolescence and patient abandonment fall under a range of post-trial issues which are currently not well examined or regulated. Trial participants are not covered by clinical trial insurance, any issues associated with their treatment which they experience after exiting the trial must be covered by their own public or private health insurance or by the goodwill of the sponsor (Harris and Gilbert 2024). While participants in the Orion EFS had concern over financial liability, they may also suffer medical, social, psychological and technical burdens. At a minimum, sponsors must at least articulate what post-trial risks and support will be offered to obtain true informed consent. According to Levy et al.’s study, participants clearly didn’t evaluate their post-trial risks and the irreversibility of the treatment appropriately, indicating a failure of the informed consent process. For instance, the potential for having seizures or causing epilepsy may not be appropriately understood, including the impacts on lifestyle, and the added difficulties the participant may then suffer by not being able to have MRIs impacting on diagnosis and treatment options for the seizures, and further risk of sudden unexpected death which may occur as a result of having a seizure in a dangerous situation. Greater efforts must be made with the informed consent process covering the post-trial period and irreversible harms. However, sponsors obligations to participants after they exit the trial cannot be waived through informed consent processes. Subsequently, all reasonable steps should be made to ensure participants are supported after they exit the trial, which may also involve an exit interview and second round of informed consent.

DISCLOSURE STATEMENT

No potential conflict of interest was reported by the author(s).

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Funding

The author(s) reported there is no funding associated with the work featured in this article.