Human clinical research has become a huge economic enterprise (Morin et al. 2002; Noah 2002). Because the human subject at the center can be so easily marginalized, many commentators recommend spec...

Public discussion of new medical trials is desirable, but not moment‐by‐moment disclosure of patients' ups and down. Nor is such disclosure necessary: the public is not entitled to all information about a trial as soon as it is available. What should be given the press, and what withheld, cannot be decided without appreciating the surprising number and intricate interrelations of the parties' needs and interests.

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number of (...) subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

Automation is inherently tied to ethical challenges because of its potential involvement in morally loaded decisions. In the present research, participants (n = 34) took part in a moral multi-trial dilemma-based task where the agent (human vs. machine) and the behavior (action vs. inaction) factors were randomized. Self-report measures, in terms of morality, consciousness, responsibility, intentionality, and emotional impact evaluation were gathered, together with electroencephalography (delta, theta, beta, upper and lower alpha, and gamma powers) and peripheral autonomic (electrodermal activity, (...) heart rate variability) data. Data showed that moral schemata vary as a function of the involved decider, and when the agent and behavior factors are crossed. Subjects did not consider machines full moral deciders to the same degree as humans and tend to morally better accept human active behavior and machine inaction. Moreover, the autonomic physiological activity might support the a-posteriori moral evaluation. In the evaluation of the agent’s consciousness, a beta ventrolateral prefrontal synchronization was detected for human action and machine inaction, while a generalized gamma synchronization occurred in artificial agent trials while rating the emotional impact of the decider’s behavior. The detected differences might point to a potential explicit and implicit asymmetry in moral reasoning toward artificial and human agents. (shrink)

On July 2, 2001, a medical milestone was reached when Robert Tools received a total artificial heart implant at Jewish Hospital in Louisville, Kentucky. Tools was implanted with an AbioCor artificial heart, one of several brands of new-generation artificial hearts that has been approved by the U.S. Food and Drug Administration for clinical trial. The AbioCor heart was developed by Abiomed of Danvers, Massachusetts.Following the surgery, physicians were guardedly enthusiastic about the device and (...) optimistic about the patient’s future. Tools, 59, has had a history of numerous heart attacks and by-pass surgery, as well as diabetes and kidney problems. He met the requirements of the AbioCor protocol because he was not a candidate for transplant, death was otherwise probable within thirty days, and other interventions were deemed ineffective. Researchers hope that strengthening his heart function will result in increased function of his other vital organs, thus prolonging the patient's life and increasing his energy. But because the device is experimental, nothing can be promised. (shrink)

Permanent implants of artificial hearts have been halted by bad results, but questions about fairness and informed consent have failed to stop manufacturers, surgeons, and hospitals from using mechanical hearts as bridges to transplant.

A member of the two federal advisory panels on artificial hearts reflects that the nuclear‐powered artificial heart, had it been developed, would have posed a physical threat to others. Today's artificial heart poses a different threat. Because of the high costs, many people may be deprived of access to other forms of medical care and other social goods.

It is widely believed to be permissible for a physician to discontinue any treatment upon the request of a competent patient. Many also believe it is never permissible for a physician to intentionally kill a patient. I argue that the prospect of deactivating a patient’s artificial heart presents us with a dilemma: either the first belief just mentioned is false or the second one is. Whichever horn of the dilemma we choose has significant implications for contemporary medical ethics.

Nancy Scheper-Hughes is one of the most prominent critics of markets in human organs. Unfortunately, Scheper-Hughes rejects the view that markets should be used to solve the current shortage of transplant organs without engaging with the arguments in favour of them. Scheper-Hughes’s rejection of such markets is of especial concern, given her influence over their future, for she holds, among other positions, the status of an adviser to the World Health Organization on issues related to global transplantation. Given her influence, (...) it is important that Scheper-Hughes’s moral condemnation of markets in human organs be subject to critical assessment. Such critical assessment, however, has not generally been forthcoming. A careful examination of Scheper-Hughes’s anti-market stance shows that it is based on serious mischaracterisations of both the pro-market position and the medical and economic realities that underlie it. In this paper, the author will expose and correct these mischaracterisations and, in so doing, show that her objections to markets in human organs are unfounded. (shrink)

Artificial placentas (APs) are technologies that mimic the human placenta to treat extremely preterm infants. Being an invasive and risky technology, it will raise important ethical questions for human trials. Hence, in this Topic Piece we provide a blueprint of further issues to investigate. First, counselling will have the double role of providing trial information as well as (non) treatment counselling. This requires extra training and the development of ad hoc decision aids to support counselling and parents’ decision-making. (...) Second, more stakeholder involvement is needed. Direct stakeholders, such as parents, clinicians, and researchers, can help develop the decision aids and provide insight on potentially overlooked issues. Society should also be involved to determine whether AP trials and implementation should be subsidized, and the ethical implications of not subsidizing. Third, a proper cost-benefit analysis should be conducted to determine the exact cost of the technology. (shrink)

Artificial devices that functionally replace internal organs are likely to be more common in the future. They are becoming more and more technologically feasible, increases in chronic diseases that can compromise various organs are anticipated, and donor organs will remain necessarily limited. More people in the future may have bodies that are partly nonorganic. How might artificial organs affect how we experience and conceptualize our bodies and how we understand the relation of the body to the experiencing, acting (...) subject, or self? Here, I focus on artificial heart devices (AHDs), including total artificial hearts (TAHs) and ventricular assist devices (VADs). While other devices, such as pacemakers and implantable cardiac defibrillators, assist the heart, I focus on devices that replace rather than assist organic function. AHDs, I argue, may have two opposing effects. On the one hand, having an AHD could alter experience, seemingly confirming that selves are shaped by the specifics of embodiment. On the other hand, AHDs are likely to encourage people to regard bodies as machines that are separable from the self. AHDs thus both confirm and undermine a body-self dualism. People with these devices may come to regard their bodies as machinelike even while having an artificial part alters their subjective experience. (shrink)

When the manufacturer of a medical device alone bears the responsibility for alerting recipients that the device may be defective, there is a certain temptation to gloss over the risk. The story of the Bjork‐Shiley Convexo‐Concave heart valve is a case in point.

### ­ In Who shall go first? A multicriteria approach to patient selection for first clinical trials of cardiac xenotransplantation, Kögel et al recommend the inclusion of patients who (1) have a (high) medical need for an allograft, (2) have the capacity to benefit from a xenograft, (3) have a ‘real’ choice between enrolment in a first-in-human clinical trial and an alternative life-sustaining treatment option and (4) have no clear record of previous non-compliance.1 As the authors discuss, patient selection (...) must promote the goal of gaining reliable and valid knowledge about the risks and benefits of cardiac xenotransplantation. While the four criteria outlined above certainly promote this goal, we argue it is crucial to add a fifth criterion emphasising the need to include diverse populations, particularly regarding sex, age, ethnicity and socioeconomic background.i In this commentary, we present two arguments for our claim and discuss the impact of neglecting diversity from the first trials on. ### The scientific rationale for including diverse populations First, including diverse populations in the first clinical trials of cardiac xenotransplantation enhances the scientific value of the data by assessing safety and efficacy among various populations. Treatment response can differ among patient (sub)groups as a result of genetic, physiological and socioeconomic factors.2 By including diverse populations from the first trials on, researchers can identify these …. (shrink)

De Bie et al. (2023) propose an organizing framework for different stages of human gestational development from conception to the viable premature. They also identify ethical considerations and con...

The lead article in this January‐February 2021 issue—the first of the Hastings Center Report's fiftieth year of publication—does not set out to change medicine. It tries instead to understand it. In “A Heart without Life: Artificial Organs and the Lived Body,” Mary Jean Walker draws on work in phenomenology and on empirical research with people who have received artificial heart devices to argue that such devices may have two very different effects on how a patient experiences (...) the body and the self. Several other pieces in this issue address the ongoing slew of patient care and health policy problems surrounding the Covid‐19 pandemic, and a special report titled Democracy in Crisis: Civic Learning and the Reconstruction of Common Purpose considers the requirements for public involvement in policy‐making about bioethical issues. (shrink)

This essay examines a challenge to common literary representations of female mental illness in the Early Modern period—the hysterical woman—in a collection of French short stories contemporary to Vesalius's De Fabrica: Jeanne Flore's Tales and Trials of Love. Jeanne Flore's tales depict several mentally disturbed female protagonists, young women prone to paroxysms of madness and self-mutilation. This study maintains that while Tales and Trials of Love superficially participates in the literary tradition that grew out of those accepted social and medical (...) beliefs, it also questions the long-accepted paradigm of female hysteria and points to a shift in the socio-medical climate. Jeanne Flore's fictional narratives suggest that mental illness no longer consists in the realignment of a uterine imbalance, but rather in the telling of personal stories, a precursor to psychoanalysis and narrative medicine. (shrink)

Race or ethnic identity, despite its imprecise categorization, is a useful means of identifying population differences in mechanisms of disease and treatment effects. Therefore, race and other arbitrary demographic and physiological variables have appropriately served as a helpful guide to clinical management and to clinical trial participation. The African-American Heart Failure Trial was carried out in African-Americans with heart failure because prior data had demonstrated a uniquely favorable effect in this subpopulation of the drug combination in (...) BiDil. The remarkable effect of the drug in reducing mortality in this study has illuminated an important new mechanism of therapy for heart failure. Application of these findings need not be confined to the population studied, but the observation highlights the need for more precise ways to identify individual responsiveness to therapy. (shrink)

In 2017 and 2019, two research teams claimed ‘proof of principle’ for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research–treatment distinction, pervasive in (...) regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a ‘beneficial treatment’. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico‐legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed. (shrink)

The heart has a high‐metabolic rate, and its “around‐the‐clock” vital role to sustain life sets it apart in a regenerative setting from other organs and appendages. The landscape of vertebrate species known to perform intrinsic heart regeneration is strongly biased toward ectotherms—for example, fish, salamanders, and embryonic/neonatal ectothermic mammals. It is hypothesized that intrinsic heart regeneration is exclusively limited to the low‐metabolic hearts of ectotherms. The biomedical field of regenerative medicine seeks to devise biologically inspired regenerative therapies (...) to diseased human hearts. Falsification of the ectothermy dependency for heart regeneration hypothesis may be a crucial prerequisite to meaningfully seek inspiration in established ectothermic regenerative animal models. Otherwise, engineering approaches to construct artificial heart components may constitute a more viable path toward regenerative therapies. A more strict definition of regenerative phenomena is generated and several testable sub‐hypotheses and experimental avenues are put forward to elucidate the link between heart regeneration and metabolism. Also see the video abstract here https://youtu.be/fZcanaOT5z8. (shrink)

Background The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. Objectives The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. Methods An observational study of protocols of randomised trials of chronic therapies (...) for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. Results 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. Conclusions The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised. (shrink)

Recent work in artificial intelligence has increasingly turned to argumentation as a rich, interdisciplinary area of research that can provide new methods related to evidence and reasoning in the area of law. Douglas Walton provides an introduction to basic concepts, tools and methods in argumentation theory and artificial intelligence as applied to the analysis and evaluation of witness testimony. He shows how witness testimony is by its nature inherently fallible and sometimes subject to disastrous failures. At the same (...) time such testimony can provide evidence that is not only necessary but inherently reasonable for logically guiding legal experts to accept or reject a claim. Walton shows how to overcome the traditional disdain for witness testimony as a type of evidence shown by logical positivists, and the views of trial sceptics who doubt that trial rules deal with witness testimony in a way that yields a rational decision-making process. (shrink)

This paper explores and ultimately affirms the surprising claim that artificial intelligence (AI) can become part of the person, in a robust sense, and examines three ethical and legal implications. The argument is based on a rich, legally inspired conception of persons as free and independent rightholders and objects of heightened protection, but it is construed so broadly that it should also apply to mainstream philosophical conceptions of personhood. The claim is exemplified by a specific technology, devices that connect (...) human brains with computers and operate by AI-algorithms. Under philosophically reasonable and empirically realistic conditions, these devices and the AI running them become parts of the person, in the same way as arms, hearts, or mental capacities are. This transformation shall be called empersonification. It has normative and especially legal consequences because people have broader and stronger duties regarding other persons (and parts of them) than regarding things. Three consequences with practical implications are: (i) AI-devices cease to exist as independent legal entities and come to enjoy the special legal protection of persons; (ii) therefore, third parties such as manufacturers or authors of software lose (intellectual) property rights in device and software; (iii) persons become responsible for the outputs of the empersonified AI-devices to the same degree that they are for desires or intentions arising from the depths of their unconscious. More generally, empersonification marks a new step in the long history of human–machine interaction that deserves critical ethical reflection and calls for a stronger value-aligned development of these technologies. (shrink)

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what (...) follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice. (shrink)

'if AI is outside your field, or you know something of the subject and would like to know more then Artificial Intelligence: The Basics is a brilliant primer.' - Nick Smith, Engineering and Technology Magazine November 2011 Artificial Intelligence: The Basics is a concise and cutting-edge introduction to the fast moving world of AI. The author Kevin Warwick, a pioneer in the field, examines issues of what it means to be man or machine and looks at advances in (...) robotics which have blurred the boundaries. Topics covered include: how intelligence can be defined whether machines can 'think' sensory input in machine systems the nature of consciousness the controversial culturing of human neurons. Exploring issues at the heart of the subject, this book is suitable for anyone interested in AI, and provides an illuminating and accessible introduction to this fascinating subject. (shrink)

The new life heralded by an artificial heart is hugely complicated: medically, socially, culturally, and experientially. In this paper, I argue that the compulsory presentation of medical data by artificial hearts can transform a patient’s prereflective experience of their own body and the world. First, I introduce the paracorporeal medical devices called artificial hearts. Second, I introduce the phenomenological approach of Merleau-Ponty, particularly his concern with prereflective, embodied awareness. Third, I consider how patients experience their bodies (...) vis a vis their hearts. I then argue that the representation of cardiac conditions by artificial hearts turns the body from the origin of experience to an object of experience. Fourth, I consider Merleau-Ponty’s notion of motor intentionality and a well-known interpretation by Dreyfus, known as absorbed or skillful coping. I argue that representations of cardiac conditions may interrupt prereflective experience and crowd-out coping. (shrink)

This article focuses on the interaction between man and machine, AI specifically, to analyse how these systems are slowly taking over roles that hitherto were thought ‘only’ for humans. More recent, as AI has stepped up in ability to learn without supervision, to recognize patterns, and to solve problems, it adopted characteristics like creativity, novelty, intentionality. These events take one to the heart of what it is to be human, and the emerging definitions of self that are increasingly central (...) to post humanist discourses. The discussion in these two threads is in philosophy of AI and is concerned with issues of consciousness, intentionality and creativity. Al as a result of causing a shift in the current anthropocentric perceptions resulted in portrayal of humans as special beings. Secondly, this exploration responds to important questions related to AI application, such as ethical, social, and existential ones. The article emphasizes a necessity to define the role of the advent of AI and its influence on the interaction between people and technology as well as the role of the social individuality in the wake of intelligent machines that mimic thinking and creativity. It seeks to prompt more specific analysis of how or why AI reduces the differences between artificial and human intelligence or increases the prospects for options expanding the notion of consciousness beyond the human-centric one. (shrink)

Clinical trials of xenotransplantation (XTx) may begin early in the next decade, with kidneys from genetically modified pigs transplanted into adult humans. If successful, transplanting pig hearts into children with advanced heart failure may be the next step. Typically, clinical trials have a specified end date, and participants are aware of the amount of time they will be in the study. This is not so with XTx. The current ethical consensus is that XTx recipients must consent to lifelong monitoring. (...) While this presents challenges to the right to withdraw in the adult population, additional and unanswered questions also linger in the paediatric population. In paediatric XTx, parents or guardians consent not only to the initial treatment of the child but also to lifelong monitoring, thus making a decision whose consequences will remain present as the child develops the capacity for assent, and finally the capacity for informed consent or refusal. This article presents and evaluates unanswered paediatric ethical questions in regard to the right to withdraw from XTx follow-up in the paediatric population. (shrink)

To most people outside the relevant laboratories and operating rooms, xenotransplants and artificial organ transplants are bizarre. While the bizarre scares many away and angers others, Lesley A. Sharp approached it and asked, What behooves medical research to take organs out of pigs and primates and design organs out of metal and plastic and use them to replace failing organs in humans? Sharp attended years of conferences, visited countless hospitals and laboratories, and interviewed engineers, scientists, and surgeons to explore (...) the choices and implicit values of decision‐makers in alternative transplantation. The Transplant Imaginary: Mechanical Hearts, Animal Parts, and Moral Thinking in Highly Experimental Science is a rich resource for philosophers who wish to expound on the morality of implanting nonhuman animal and mechanical organs into humans. The author's thorough ethnographic survey of xeno‐ and biomechanical transplant research leads well into two lines of questioning. First, how ethical is the pursuit of alternative transplant? Second, what is essential for transplant researchers to do their jobs ethically? (shrink)

In the ever-evolving landscape of Artificial Intelligence in Healthcare (AIH), understanding the entities and legal frameworks governing its research and development is crucial. This report delves into the intricacies of AIH in Malaysia, undertaking a comprehensive literature search on scientific databases, government portals, and news sources. Additionally, bibliometric analysis has been concurrently conducted to discern trends and developments in AIH over the years. Notably, the interest in AIH has seen a consistent rise since 2017, marked by a growing number (...) of use cases (25 reported here) developed by both local and foreign innovators and applicators. Despite this surge in research and adoption, Malaysia lacks direct legislation specifically addressing AIH technologies, leaving them subject to 11 existing laws. This lack of clear oversight is compounded by the insufficient expertise within local regulatory and ethical bodies to effectively assess AIH research and deployment. The resultant challenges include bureaucratic hurdles for AIH innovators and applicators, raising ethical concerns related to patient autonomy, privacy, data management, AI robustness, and liability. To address these issues, this paper recommends: (1) adopting international ethical guidelines for AIH, (2) enhancing public awareness and education on AI technologies, and (3) promoting AIH research through clinical or silent trials to improve oversight and foster innovation. (shrink)

The Heart and Flower task is used worldwide to measure age-dependent and individual differences in executive functions and/or cognitive control. The task reliably maps age and individual differences and these have consistently been found to be predictive for different aspects of school readiness and academic achievement. The idea has been put forward that there is a developmental shift in how children approach such a task. While 6-year-olds’ tend to adapt their task strategy ad hoc and reactively, older children increasingly (...) engage in proactive cognitive control. Proactive cognitive control entails finding the right response speed without risking errors, always dependent on the cognitive conflict. The main goal of the present contribution was to examine children’s adjustments of response speed as a function of age and cognitive conflict by addressing RTs surrounding errors (i.e., errors and post-error trials). Data from a large sample with three age groups was used (N = 106 6-year-olds’ with a mean age of 6 years; 3 months; N = 108 7-year-olds’ with a mean age of 7 years; 4 months; N = 78 8-year-olds’ with a mean age of 8 years; 1 month). Response speed adjustments and the development thereof were targeted both across the Flower and Mixed block, respectively, and within these blocks focusing on errors and post-error slowing. Results revealed evidence for a developmental shift toward more efficient proactive cognitive control between 6 and 8 years of age, with the older but not the younger children strategically slowing down in the Mixed block and smoother post-error slowing. At the same time, we found that even the youngest age group has emerging proactive cognitive control skills at their disposal when addressing post-error slowing in the Flower block. The present study thus tracks the early roots of later efficient executive functions and cognitive control, contributes to a better understanding of how developmental progression in cognitive control is achieved, and highlights new avenues for research in this domain. (shrink)