L’implantation d’une nouvelle technologie est une étape de la translation d’une découverte vers une application clinique. De nombreux modèles ont été proposés pour étudier une telle translation ; celui de Goering, Holland et Kelley met de l’avant des priorités qui résonnent avec la bioéthique. Nous proposons l’application d’un outil issu des sciences de l’implantation, le Consolidated Framework for Implementation Research (CFIR), pour identifier les enjeux éthiques d’une nouvelle technologie. Cet outil est conçu pour identifier les barrières et facilitateurs (...) de l’implantation d’une technologie, et par le fait même s’inscrit dans le modèle de la recherche translationnelle. Nous prenons en exemple le test génomique prénatal non invasif (TGPNI). Ce test est offert dans certaines provinces du Canada en deuxième intention pour les personnes enceintes ayant une haute probabilité d’avoir un foetus avec une aneuploïdie. Des innovations potentielles du TGPNI sont de l’offrir comme test de première intention et d’étendre le nombre de conditions génétiques dépistées. Nous proposons donc d’utiliser le CFIR pour identifier les enjeux éthiques qui découlent des barrières et facilitateurs de ces innovations du TGPNI. En identifiant les barrières et facilitateurs de l’implantation d’une technologie, cet outil permet aux bioéthiciens de recourir à un outil éprouvé d’une autre discipline pour étudier des enjeux éthiques. Les bioéthiciens peuvent alors se tourner vers leurs outils traditionnels pour identifier les enjeux éthiques que soulèvent ces éléments. Notre proposition est un exemple parmi d’autres possibles de ce que cette approche peut accomplir : identifier d’une manière innovatrice des enjeux éthiques d’une nouvelle technologie. (shrink)

Background Non-invasive prenatal testing (NIPT), which can screen for aneuploidies such as trisomy 21, is being implemented in several public healthcare systems across Europe. Comprehensive communication and information have been highlighted in the literature as important elements in supporting women’s reproductive decision-making and addressing relevant ethical concerns such as routinisation. Countries such as England and France are adopting broadly similar implementation models, offering NIPT for pregnancies with high aneuploidy probability. However, we do not have a deeper understanding of (...) how professionals’ counselling values and practices may differ between these contexts. Methods In this paper, we explore how professionals in England and France support patient decision-making in the provision of NIPT and critically compare professional practices and values. We draw on data from semi-structured interviews with healthcare professionals. Results Both English and French professionals emphasised values relating to patient choice and consent. However, understandings and application of these values into the practice of NIPT provision differed. English interviewees placed a stronger emphasis on interpreting and describing the process of counselling patients and clinical care through a “principle” lens. Their focus was on non-directiveness, standardisation, and the healthcare professional as “decision-facilitator” for patients. French interviewees described their approach through a “procedural” lens. Their focus was on formal consent, information, and the healthcare professional as “information-giver”. Both English and French professionals indicated that insufficient resources were a key barrier in effectively translating their values into practice. Conclusion Our findings illustrate that supporting patient choice in the provision of NIPT may be held as an important value in common on a surface level, but can be understood and translated into practice in different ways. Our findings can guide further research and beneficially inform practice and policy around NIPT provision. (shrink)

Prenatal screening for foetal abnormalities such as Down's syndrome differs from other forms of population screening in that the usual aim of achieving health gains through treatment or prevention does not seem to apply. This type of screening leads to no other options but the choice between continuing or terminating the pregnancy and can only be morally justified if its aim is to provide meaningful options for reproductive choice to pregnant women and their partners. However, this (...) aim should not be understood as maximizing reproductive choice per se. Only if understood as allowing prospective parents to avoid suffering related to living with serious disorders and handicaps can prenatal screening be a publicly or collectively funded programme. The alternative of moving prenatal testing outside the healthcare system into the private sector is problematic, as it makes these tests accessible only to those who can afford to pay for it. New developments in prenatal screening will have to be assessed in terms of whether and to what extent they either contribute to or undermine the stated aim of providing meaningful options for reproductive choice. In the light of this criterion, this article discusses the introduction of the new non-invasive prenatal test , the tendency to widen the scope of follow-up testing, as well as the possible future scenarios of genome-wide screening and ‘prenatal personalised medicine’. The article ends with recommendations for further debate, research and analysis. (shrink)

Prenatal screening for foetal abnormalities such as Down's syndrome differs from other forms of population screening in that the usual aim of achieving health gains through treatment or prevention does not seem to apply. This type of screening leads to no other options but the choice between continuing or terminating the pregnancy and can only be morally justified if its aim is to provide meaningful options for reproductive choice to pregnant women and their partners. However, this (...) aim should not be understood as maximizing reproductive choice per se. Only if understood as allowing prospective parents to avoid suffering related to living with (a child with) serious disorders and handicaps can prenatal screening be a publicly or collectively funded programme. The alternative of moving prenatal testing outside the healthcare system into the private sector is problematic, as it makes these tests accessible only to those who can afford to pay for it. New developments in prenatal screening will have to be assessed in terms of whether and to what extent they either contribute to or undermine the stated aim of providing meaningful options for reproductive choice. In the light of this criterion, this article discusses the introduction of the new non‐invasive prenatal test (NIPT), the tendency to widen the scope of follow‐up testing, as well as the possible future scenarios of genome‐wide screening and ‘prenatal personalised medicine’. The article ends with recommendations for further debate, research and analysis. (shrink)

Expanded non-invasive prenatal testing (NIPT) has provoked ethical concerns about its justifiable scope. In this paper, we evaluate the role of the child’s right to an open future in setting the scope of NIPT. This ‘open future principle’ has been cited in arguments both limiting and expanding parental freedoms. This moral right holds that adult autonomy rights which children cannot yet exercise should nonetheless be protected until they can. Its purpose is to protect the future autonomy of the (...) child as a future adult. Several authors have extended this rationale from child to fetus. However, the right was not anticipated to apply to the fetus, a non-legal entity in many jurisdictions. The aim of this paper is to reconsider whether this principle is useful to help deliberate the scope of NIPT. We find that extending the open future principle to delineate the scope of NIPT is theoretically flawed. We contend that in the prenatal context its value primarily lies with counselling for prenatal screening where it can be used to encourage parents’ reflection on the implications of knowing for the sake of knowing on their future children and their relationship with them. (shrink)

BackgroundThe introduction and wide application of non-invasive prenatal testing (NIPT) has triggered further evolution of routines in the practice of prenatal diagnosis. ‘Routinization’ of prenatal diagnosis however has been associated with hampered informed choice and eugenic attitudes or outcomes. It is viewed, at least in some countries, with great suspicion in both bioethics and public discourse. However, it is a heterogeneous phenomenon that needs to be scrutinized in the wider context of social practices of reproductive genetics. (...) In different countries with their different regulatory frameworks, different patterns of routines emerge that have different ethical implications.This paper discusses an ethics of routines informed by the perspectives of organizational sociology and psychology, where a routine is defined as a repetitive, recognizable pattern of interdependent organizational actions that is carried out by multiple performers. We favour a process approach that debunks the view – which gives way to most of the concerns – that routines are always blindly performed. If this is so, routines are therefore not necessarily incompatible with responsible decision-making. Free and informed decision-making can, as we argue, be a key criterion for the ethical evaluation of testing routines. If free and informed decision-making by each pregnant woman is the objective, routines in prenatal testing may not be ethically problematic, but rather are defensible and helpful. We compare recent experiences of NIPT routines in the context of prenatal screening programmes in Germany, Israel and the Netherlands. Notable variation can be observed between these three countries (i) in the levels of routinization around NIPT, (ii) in the scope of routinization, and (iii) in public attitudes toward routinized prenatal testing.ConclusionAn ethics of routines in the field of prenatal diagnostics should incorporate and work with the necessary distinctions between levels and forms of routines, in order to develop sound criteria for their evaluation. (shrink)

Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non‐invasive prenatal testing (NIPT) in first‐trimester prenatal screening programmes: amongst others its procedural ease—it only requires a blood draw and reaches high levels of reliability—might hinder women’s understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition (...) and use of informed consent compared to informed choice, and for a focus on value‐consistent choices and personalized informational preferences. We argue for a three‐step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women’s values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical‐technical information and are asked to make a decision about screening; (3) during post‐test counselling, women are supported in decision‐making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre‐test) counselling, where techniques for expanding genome analysis and burdensome test‐outcomes challenge counselling of patients. (shrink)

Background Prenatal genetic testing, in particular non-invasive prenatal testing (NIPT), as well as screening for risks associated with pregnancy, and counseling, play pivotal roles in reproductive healthcare, offering valuable information about the health of the fetus to expectant parents. This study aims to delve into the perspectives and experiences of women considering genetic testing and screening during pregnancy, focusing on their decision-making processes and the implications for informed consent. Methods A nationwide qualitative study was conducted (...) in Switzerland, involving in-depth interviews with women who were 1 to 2 years post-partum, covered by basic compulsory Swiss insurance, including women with a migration background. Thematic analysis was employed to identify key themes and patterns in the data. Results The findings underscore the significance of effective communication during prenatal counseling, suggesting that healthcare providers could not only convey technical information but also support women in their decision-making processes. Women need comprehensive information about genetic testing and its implications, as well as the reasons for screening during pregnancy, as there might be a need to bridge knowledge gaps and clarify misconceptions. Furthermore, the study highlights the multifaceted nature of decision-making, with women considering factors such as uncertainty, values, emotional responses, and societal support systems. The concept of acceptance emerged as a crucial theme, with some women expressing their readiness to love and accept their child, regardless of genetic anomalies or disabilities. Conclusion This study offers valuable insights into the perspectives and needs of women regarding prenatal genetic testing, screening, and counseling in Switzerland. It underscores the importance of enhancing the clinical interaction and informed consent process by providing comprehensive information, addressing misconceptions, and supporting women in decision-making about pregnancy management and the management of the child’s health, following prenatal genetic testing, including NIPT. These findings can inform healthcare providers and policymakers in improving the quality of prenatal counseling, ensuring informed consent, and supporting women in making well-informed and meaningful decisions about genetic testing, and on the use of screening during pregnancy. (shrink)

Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non-invasive prenatal testing (NIPT) in first-trimester prenatal screening programmes: amongst others its procedural ease—it only requires a blood draw and reaches high levels of reliability—might hinder women’s understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition (...) and use of informed consent compared to informed choice, and for a focus on value-consistent choices and personalized informational preferences. We argue for a three-step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women’s values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical-technical information and are asked to make a decision about screening; (3) during post-test counselling, women are supported in decision-making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre-test) counselling, where techniques for expanding genome analysis and burdensome test-outcomes challenge counselling of patients. (shrink)

Non-invasive prenatal testing is at the forefront of prenatal screening. Current uses for NIPT include fetal sex determination and screening for chromosomal disorders such as trisomy 21. However, NIPT may be expanded to many different future applications. There are a potential host of ethical concerns around the expanding use of NIPT, as examined by the recent Nuffield Council report on the topic. It is important to examine what NIPT might be used for before these possibilities (...) become consumer reality. There is limited research exploring views of women on possible future uses of NIPT, particularly those of women who have undergone NIPT. In this study, we examined the views of women who undertook NIPT previously on the acceptability of and interest levels in using NIPT for a number of current and possible future applications. These included several medical conditions encompassing psychiatric, neurodevelopmental and adult-onset conditions as well as non-medical traits such as intelligence. One thousand women were invited to participate and 235 eligible surveys were received. Women generally reported an interest in using NIPT for medical conditions that severely impacted quality of life and with an onset earlier in life and stressed the importance of the accuracy of the test. Concerns were raised about the use of NIPT for non-medical traits. Respondents indicated that termination of pregnancy was not their only reason for testing, particularly in the case of sex. These results can further inform the ethical debate around the increasing integration of NIPT into healthcare systems. (shrink)

This article investigates the role of historical references and arguments in the current policy debate on non‐invasive prenatal testing (NIPT) in Germany. It analyses major documents and opinion statements, including the recent parliamentary debate (2019). The implementation of NIPT is accompanied by concerns and strong criticism, particularly in Germany. Many perceive the new test to be a problematic step that facilitates selective practices and is reminiscent of eugenics. Analysis of the German policy discourse shows that ‘eugenics’, and even (...) more strongly, ‘selection’, are pivotal terms for rejecting NIPT and its coverage by public health insurance. They touch on a historical dimension in public deliberation, namely the fundamental distancing from the inhuman practices of the National Socialist period and anything that resembles them. However, using these terms to criticize prenatal genetic testing is controversial, and recent discourse demonstrates their avoidance as well, with many supporters of a limited coverage by public health insurance contrasting their approach with more widespread screening. Here, ‘screening’ has a negative connotation, and functions to demarcate the debate in a way that may reflect distance from certain modes of historical reasoning, but still expresses a special need to reconcile prenatal testing with the principles of dignity, inclusion and diversity. This article aims to elucidate the concerns involved in the national debates on prenatal testing and to increase awareness of the historical dimensions of the language and reasoning with which such methods are negotiated today and in future. (shrink)

Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and (...) the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent ‘reproductive autonomy’ is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue. (shrink)

Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk‐assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and (...) the delivery.Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non‐invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable.This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent ‘reproductive autonomy’ is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy‐related problems, non‐directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue. (shrink)

Riordan, Marcia Recent advances in genetic technology may mean that the brave new world really is almost here. Non-invasive prenatal genetic diagnosis could finally allow hundreds of thousands of genetic traits to be determined with just one maternal blood test. This could bring genetic screening of the unborn child to a whole new level and mean that as a society we face a new set of challenges in areas such as disability rights, abortion and informed consent.

Developments in Non-Invasive Prenatal Testing (NIPT) and cell-free fetal DNA analysis raise the possibility that antenatal services may soon be able to support couples in non-invasively testing for, and diagnosing, an unprecedented range of genetic disorders and traits coded within their unborn child’s genome. Inevitably, this has prompted debate within the bioethics literature about what screening options should be offered to couples for the purpose of reproductive choice. In relation to this problem, the European Society of Human (...) Genetics (ESHG) and American Society of Human Genetics (ASHG) tentatively recommend that any expansion of this type of screening, as facilitated by NIPT, should be limited to serious congenital and childhood disorders. In support of this recommendation, the ESHG and ASHG cite considerations of distribution justice. Notably, however, an account of justice in the organization and provision of this type of screening which might substantiate this recommendation has yet to be developed. This paper attempts to redress this oversight through an investigation of Norman Daniels’ theory of Just health: meeting health needs fairly. In line with this aim, the paper examines what special moral importance (for Just health) screening for the purpose of reproductive choice might have where concerning serious congenital and childhood disorders in particular. The paper concludes that screening for reproductive choice where concerning serious congenital and childhood disorders may be important for providing women with fair opportunity to protect their health (by either having or not having an affected child). (shrink)

From an ethical point of view, there is an important distinction between two types of prenatal screening. The first of these targets maternal or foetal conditions (e.g., infectious diseases, blood group sensitization) where early detection allows for interventions that improve the chances of a healthy pregnancy outcome. The second screens for foetal conditions such as Down syndrome, where a timely diagnosis in most cases only allows for a choice between preparation for a child with special needs or termination (...) of the pregnancy. Whereas the former makes an easy fit with the prevention aim of most other population screening programmes, the latter does not. In order to steer clear from a possible eugenic reading of its aim, a wide international consensus has emerged for the view that prenatal screening of this type should have the atypical aim of helping women (couples) to make autonomous reproductive choices, rather than reducing the birth prevalence of the relevant disorders. However, keeping these types of prenatal screening apart may become increasingly difficult given the development of tests, such as the Non‐Invasive Prenatal Test, which cannot only be used for both types of screening but may also lead to interconnected findings on both sides of the divide. This makes it an urgent question: What the aim or aims of this new hybrid screening should be? As neither ‘prevention’ nor ‘autonomy’ will do, we argue for a normative framework that gives both aims their due, while recognizing the tensions between them. (shrink)

BackgroundEmpirical research can become relevant for bioethics in at least two ways. First, by informing the development or refinement of ethical recommendations. Second, by evaluating how ethical recommendations are translated into practice. This study aims to investigate the scope and objectives of empirical studies evaluating how ethical recommendations are translated into practice. MethodsA sample of the latest 400 publications from four bioethics journals was created and screened. All publications were included if they met one of the following three criteria: (1) (...) evaluative empirical research, (2) non-evaluative empirical research and (3) borderline cases. For all publications categorized as evaluative empirical research we analyzed which objects (norms and recommendations) had been evaluated.Results234 studies were included of which 54% (n = 126) were categorized as non-evaluative empirical studies, 36% (n = 84) as evaluative empirical studies, and 10% (n = 24) as borderline cases. The object of evaluation were aspirational norms in 5 of the 84 included evaluative empirical studies, more specific norms in 14 (16%) studies and concrete best practices in 65 (77%) studies. The specific best practices can be grouped under five broader categories: ethical procedures, ethical institutions, clinical or research practices, educational programs, and legal regulations.ConclusionsThis mapping study shows that empirical evaluative studies can be found at all stages in the translational process from theory to best practices. Our study suggests two intertwined dimensions for structuring the field of evaluative/translational empirical studies in bioethics: First, three broader categories of evaluation objects and second five categories for types of best practices.Trial registration: The methodology used was described in a study protocol that was registered publicly on the Open Science Framework (https://osf.io/r6h4y/). (shrink)

In “Non-invasive prenatal testing for ‘non-medical’ traits: Ensuring consistency in ethical decision-making,” Bowman-Smart et al. (2023) lay out arguments both for and against the potential use of...

The introduction of non-invasive prenatal testing in healthcare systems around the world offers an opportunity to reconsider funding policies for prenatal screening. In some countries with universal access healthcare systems, pregnant women and their partners are asked to pay for NIPT. In this paper, we discuss two important rationales for charging women for NIPT: to prevent increased uptake of NIPT and to promote informed choice. First, given the aim of prenatal screening, high or low (...) uptake rates are not intrinsically desirable or undesirable. Using funding policies to negatively affect uptake, however, is at odds with the aim of screening. Furthermore, copayment disproportionally affects those of lower socioeconomic status, which conflicts with justice requirements and impedes equal access to prenatal screening. Second, we argue that although payment models may influence pregnant women’s choice behaviours and perceptions of the relevance of NIPT, the copayment requirement does not necessarily lead to better-informed choices. On the contrary, external influences on women’s personal choices for or against prenatal screening should ideally be avoided. To improve informed decision-making, healthcare systems should instead invest in adequate non-directive, value-focused pretest counselling. This paper concludes that requiring copayments for NIPT in universal access healthcare systems fails to promote reproductive autonomy and is unfair. (shrink)

Background: Patients undergoing invasive neurosurgical procedures offer researchers unique opportunities to study the brain. Deep brain stimulation patients, for example, may participate in research during the surgical implantation of the stimulator device. Although this research raises many ethical concerns, little attention has been paid to basic studies, which offer no therapeutic benefits, and the value of patient-participant perspectives.Methods: Semi-structured interviews were conducted with fourteen individuals across two studies who participated in basic intraoperative research during their deep brain stimulator (...) surgery. Interviews explored interpretations of risks and benefits, enrollment motivations, and experiences of participating in awake brain research. Reflexive thematic analysis was conducted.Results: Seven themes were identified from participant narratives, including robust attitudes of trust, high valuations of basic science research, impacts of the surgical context, and mixed experiences of participation.Conclusion: We argue that these narratives raise the potential for a translational misconception and motivate intraoperative re-consent procedures. (shrink)

The notion of being a burden to others is mostly discussed in the context of care‐intensive diseases or end‐of‐life decisions. But the notion is also crucial in decision‐making at the beginning of life, namely regarding prenatal testing. Ever more sophisticated testing methods, especially non‐invasive prenatal testing (NIPT), allow the detection of genetic traits in the unborn child that may cause disabilities. A positive result often influences the decision of the pregnant women towards a termination of the pregnancy. (...) Thus, critics claim that these testing methods send a negative message to people with disabilities. At the core of this is what we call the burden assumption. This assumption claims that children with disabilities are necessarily a burden to others, especially to their parents and other family members. In this paper, we discuss what being a burden to others means in this context and how such an attitude can be avoided without restraining reproductive autonomy. A closer examination shows that the burden assumption is mostly based on misinformation and a false model of disability. Empirical studies as well as narrative evidence from parents who raise a child with disabilities show that the burden assumption is wrong. Raising a child with disabilities does not necessarily mean a decrease in the quality of life. We show how the burden assumption can be challenged through an advanced genetic counselling that combines empirical evidence with narratives from a first‐person perspective. (shrink)

The scope of noninvasive prenatal testing (NIPT) could expand in the future to include detailed analysis of the fetal genome. This will allow for the testing for virtually any trait with a genetic contribution, including “non-medical” traits. Here we discuss the potential use of NIPT for these traits. We outline a scenario which highlights possible inconsistencies with ethical decision-making. We then discuss the case against permitting these uses. The objections include practical problems; increasing inequities; increasing the burden of choice; (...) negative impacts on the child, family, and society; and issues with implementation. We then outline the case for permitting the use of NIPT for these traits. These include arguments for reproductive liberty and autonomy; questioning the labeling of traits as “non-medical”; and the principle of procreative beneficence. This summary of the case for and against can serve as a basis for the development of a consistent and coherent ethical framework. (shrink)

Over the past decade, non-invasive prenatal testing (NIPT) has been adopted into routine obstetric care to screen for fetal sex, trisomies 21, 18 and 13, sex chromosome aneuploidies and fetal sex determination. It is predicted that the scope of NIPT will be expanded in the future, including screening for adult-onset conditions (AOCs). Some ethicists have proposed that using NIPT to detect severe autosomal AOCs that cannot be prevented or treated, such as Huntington’s disease, should only be offered (...) to prospective parents who intend to terminate a pregnancy in the case of a positive result. We refer to this as the ‘conditional access model’ (CAM) for NIPT. We argue against CAM for NIPT to screen for Huntington’s disease or any other AOC. Next, we present results from a study we conducted in Australia that explored NIPT users’ attitudes regarding CAM in the context of NIPT for AOCs. We found that, despite overall support for NIPT for AOCs, most participants were not in favour of CAM for both preventable and non-preventable AOCs. Our findings are discussed in relation to our initial theoretical ethical theory and with other comparable empirical studies. We conclude that an ‘unconditional access model’ (UAM), which provides unrestricted access to NIPT for AOCs, is a morally preferable alternative that avoids both CAM’s fundamental practical limitations and the limitations it places on parents’ reproductive autonomy. (shrink)

Introductory and advanced textbooks in bioethics focus almost entirely on issues that disproportionately affect disabled people and that centrally deal with becoming or being disabled. However, such textbooks typically omit critical philosophical reflection on disability, lack engagement with decades of empirical and theoretical scholarship spanning the social sciences and humanities in the multidisciplinary field of disability studies, and avoid serious consideration of the history of disability activism in shaping social, legal, political, and medical understandings of disability over the last fifty (...) years. For example, longstanding discussions on topics such as euthanasia, physician aid-in-dying, pre-implantation genetic diagnosis, prenatal testing, selective abortion, enhancement, patient autonomy, beneficence, non-maleficence, and health care rationing all tend to be premised on shared and implicit assumptions regarding disability, especially in relation to quality of life, yet with too little recognition of the way that “disability” is itself a topic of substantial research and scholarly disagreement across multiple fields. This is not merely a concern for academic and medical education; as an applied field tied to one of the largest economic sectors of most industrialized nations, bioethics has a direct impact on healthcare education, practice, policy, and, thereby, the health outcomes of existing and future populations. It is in light of these pressing issues that the Disability Bioethics Reader is the first reader to introduce students to core bioethical issues and concepts through the lens of critical disability studies and philosophy of disability. The Disability Bioethics Reader will include over thirty-five chapters covering key areas such as: critical histories and state-of-the-field analyses of modern medicine, bioethics, disability studies, and philosophy of medicine; methods in bioethics; concerns at the edge- and end-of-life; enhancement; disability, quality of life, and well-being; prenatal testing and abortion; invisible disabilities; chronic illness; healthcare justice; genetics and genomics; intellectual disability and neurodiversity; ethics and diagnosis; and epistemic injustice in healthcare. (shrink)

Non-invasive prenatal testing is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples (...) to test purely ‘for information’. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT ‘purely for information’, including the competing interests of the prospective parents and the future child, and the acceptability of testing for ‘frivolous’ reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult-onset conditions, carrier status or non-serious traits presenting in childhood would be unacceptable. (shrink)

If I told you that screening technologies are iteratively transforming how people experience pregnancy and early parenting, you might take notice. If I mentioned that a new class of newborn patients was being created and that particular forms of parental vigilance were emerging, you might want to know more. If I described how the particular stories told about screening in public, combined with parents’ fierce commitment to safeguarding their children’s health, make it difficult for problematic experiences with (...) class='Hi'>screening to translate into negative opinions about it, you would most likely be intrigued. An extensive qualitative literature documents all these social phenomena, and more, in connection with the spread of prenatal and newborn screening. So why is it, then, that commentators frequently assert that the predicted psychosocial impact of increased screening and testing associated with “the genomic revolution” has been far less severe and worthy of attention than predicted? How can or should social science “evidence” that sits outside adopted measurement conventions be considered? Why is it that summary statements about the psychosocial impact of genomic information often ignore qualitative evidence, or sideline it as relevant only for improving communication among patients, clinicians, and public health systems? This essay addresses such questions, using qualitative research on prenatal and newborn screening as a case study for illustrating the broad methodological, ideological, and dialogical issues at stake. (shrink)

A new landscape of prenatal testing is presently developing, including new techniques for risk-reducing, non-invasive sampling of foetal DNA and drastically enhanced possibilities of what may be rapidly and precisely analysed, surrounded by a growing commercial genetic testing industry and a general trend of individualization in healthcare policies. This article applies a set of established ethical notions from past debates on PNT for analysing PNT screening-programmes in this new situation. While some basic challenges of PNT stay untouched, (...) the new development supports a radical individualization of how PNT screening is organized. This reformation is, at the same time, difficult to reconcile with responsible spending of resources in a publicly funded healthcare context. Thus, while the ethical imperative of individualization holds and applies to PNT, the new landscape of PNT provides reasons to start rolling back the type of mass-screening programmes currently established in many countries. Instead, more limited offers are suggested, based on considerations of severity of conditions and optimized to simultaneously serve reproductive autonomy and public health within an acceptable frame of priorities. The new landscape of PNT furthermore underscores the ethical importance of supporting and including people with disabilities. For the very same reason, no ban on what may be analysed using PNT in the new landscape should be applied, although private offers must, of course, conform to strict requirements of respecting reproductive autonomy and what that means in terms of counselling. (shrink)

BackgroundPrevention of mother to child transmission of HIV remains a key public health priority in most developing countries. The provider Initiated Opt – Out Prenatal HIV Screening Approach, recommended by the World Health Organization lately has been adopted and translated into policy in most Sub – Saharan African countries. To better ascertain the ethical reasons for or against the use of this approach, we carried out a literature review of the ethics literature.MethodsPapers published in English and French Languages (...) between 1990 and 2015 from the following data bases were searched: Pubmed, Cochrane literature, Embase, Cinhal, Web of Science and Google Scholar. After screening from 302 identified relevant articles, 21 articles were retained for the critical review.DiscussionMost authors considered this approach ethically justifiable due to its potential benefits to the mother, foetus and society. The breaching of respect for autonomy was considered acceptable on the grounds of libertarian paternalism. Most authors considered the Opt - Out approach to be less stigmatizing than the Opt - In. The main arguments against the Opt - Out approach were: non respect of patient autonomy, informed consent becoming a meaningless concept and the HIV test becoming compulsory, risk of losing trust in health care providers, neglect of social and psychological implications of doing an HIV test, risk of aggravation of stigma if all tested patients are not properly cared for and neglect of sociocultural peculiarities.ConclusionsThe Opt – Out approach could be counterproductive in case gender sensitive issues within the various sociocultural representations are neglected, and actions to offer holistic care to all women who shall potentially test positive for HIV were not effectively ascertained. The Provider Initiated Opt – Out Prenatal HIV Screening option remains ethically acceptable, but deserves caution, active monitoring and evaluation within the translation of this approach into to practice. (shrink)

Bunnik and colleagues argued that financial barriers do not promote informed decision-making prior to prenatal screening and raise justice concerns. If public funding is provided, however, it would seem to be important to clarify its intentions and avoid any unwarranted appearance of a medical utility of the testing.

Non-Invasive Prenatal Testing is a technology which provides information about fetal genetic characteristics very early in pregnancy by examining fetal DNA obtained from a sample of maternal blood. NIPT is a morally complex technology that has advanced quickly to market with a strong push from industry developers, leaving many areas of uncertainty still to be resolved, and creating a strong need for health policy that reflects women’s social and ethical values. We approach the need for ethical policy-making by (...) studying the use of NIPT and emerging policy in the province of Ontario, Canada. Using an adapted version of constructivist grounded theory, we conducted interviews with 38 women who have had personal experiences with NIPT. We used an iterative process of data collection and analysis and a staged coding strategy to conduct a descriptive analysis of ethics issues identified implicitly and explicitly by women who have been affected by this technology. The findings of this paper focus on current ethical issues for women seeking NIPT, including place in the prenatal pathway, health care provider counselling about the test, industry influence on the diffusion of NIPT, consequences of availability of test results. Other issues gain relevance in the context of future policy decisions regarding NIPT, including funding of NIPT and principles that may govern the expansion of the scope of NIPT. These findings are not an exhaustive list of all the potential ethical issues related to NIPT, but rather a representation of the issues which concern women who have personal experience with this test. Women who have had personal experience with NIPT have concerns and priorities which sometimes contrast dramatically with the theoretical ethics literature. These findings suggest the importance of engaging patients in ethical deliberation about morally complex technologies, and point to the need for more deliberative patient engagement work in this area. (shrink)

BackgroundBreakthroughs in animal studies make the topic of human application of ectogenesis for medical and non-medical purposes more relevant than ever before. While current data do not yet demonstrate a reasonable expectation of clinical benefit soon, several groups are investigating the feasibility of artificial uteri for extracorporeal human gestation.Main textThis paper offers the first comprehensive and up to date discussion of the most important pros and cons of human ectogenesis in light of clinical application, along with an examination of crucial (...) ethical (and legal) issues that continued research into, and the clinical translation of, ectogenesis gives rise to. The expected benefits include advancing prenatal medicine, improving neonatal intensive care, and providing a novel pathway towards biological parenthood. This comes with important future challenges. Prior to human application, important questions have to be considered concerning translational research, experimental use of human fetuses and appropriate safety testing. Key questions are identified regarding risks to ectogenesis’ subjects, and the physical impact on the pregnant person when transfer from the uterus to the artificial womb is required. Critical issues concerning proportionality have to be considered, also in terms of equity of access, relative to the envisaged application of ectogenesis. The advent of ectogenesis also comes with crucial issues surrounding abortion, extended fetal viability and moral status of the fetus.ConclusionsThe development of human ectogenesis will have numerous implications for clinical practice. Prior to human testing, close consideration should be given to whether (and how) ectogenesis can be introduced as a continuation of existing neonatal care, with due attention to both safety risks to the fetus and pressures on pregnant persons to undergo experimental and/or invasive procedures. Equally important is the societal debate about the acceptable applications of ectogenesis and how access to these usages should be prioritized. It should be anticipated that clinical availability of ectogenesis, possibly first as a way to save extremely premature fetuses, may spark demand for non-medical purposes, like avoiding physical and social burdens of pregnancy. (shrink)

ABSTRACT Research groups around the world are developing non‐invasive methods of prenatal genetic diagnosis, in which foetal cells are obtained by maternal blood test. Meanwhile, an increasing number of genetic tests are sold directly to the public. I extrapolate from these developments to consider a scenario in which PNGD self‐testing kits are sold directly to the public. Given the opposition to over‐the‐counter genetic tests and the continuing controversy surrounding PNGD, it is reasonable to expect objections to PNGD self‐testing (...) kits. I focus on one potential objection, that PNGD self‐testing kits would undermine the autonomy of potential test subjects. More specifically, that ‘direct to the public’ PNGD would fail to ensure that consumers exercise autonomy in the following PNGD‐related choices: • Should I use PNGD? • Based on the results of the PNGD test, should I continue or terminate my pregnancy? Under the current system, PNGD is provided by health care practitioners, who are required to counsel women both before and after the test. In contrast, ‘direct to the public’ PNGD would allow women to make their PNGD‐related decisions outside the context of the health care system. I compare these two decision‐making contexts, arguing that the health care system is not unequivocally better at promoting the autonomy of potential test subjects. Therefore the promotion of autonomy does not constitute a strong argument against such test kits. Other objections may be more persuasive, so I do not offer an overall assessment of the acceptability of ‘direct to the public’ PNGD. (shrink)

New technologies create new complexities. Since non-invasive prenatal tests (NIPTs) were first introduced, keeping pace with complexity constitutes an ongoing task for medical societies, politics, and practice. NIPTs analyse the chromosomes of the fetus from a small blood sample. Initially, NIPTs were targeted at detecting trisomy 21 (Down syndrome): meanwhile there are sequencing techniques capable of analysing the entire genome of the unborn child. These yield findings of unclear relevance for the child’s future life, resulting in new responsibility (...) structures and dilemmas for the parents-to-be.The industry’s marketing strategies overemphasize the benefits of the tests while disregarding their consequences. This paper chooses the opposite path: starting with the underestimated consequences, it focuses on adverse developments and downsides. Disparities, paradoxes, and risks associated with NIPTs are illustrated, ethical conflicts described. Indications that new technologies developed to solve problems create new ones are examined. In the sense of critical thinking, seemingly robust knowledge is scrutinized for uncertainties and ambiguities. It analyses how the interplay between genetic knowledge and social discourse results in new dimensions of responsibility not only for parents-to-be, but also for decision-makers, authorities, and professional societies, illustrated by a review of different national policies and implementation programmes. As shown by the new NIPT policy in Norway, the consequences can be startling. Finally, a lawsuit in the United States illustrates how an agency can risk forfeiting its legitimation in connection with the inaccuracy of NIPTs. (shrink)

Hilary Bowman-Smart et al. (2023) have rightly pointed out that one of the recurring criticisms of the use of noninvasive prenatal testing (NIPT) for non-medical trait prediction is the probabilist...

It is unarguable that the implementation and use of noninvasive prenatal testing (NIPT) should be critical and appropriate. After all, decisions that influence when and how to have children have ut...

Prenatal ultrasound is a non-invasive diagnostic examination. Despite the recognized diagnostic value, this technology raises complex ethical questions. The aim of this study is to provide a comprehensive analysis that coherently maps the ethical challenges raised by prenatal ultrasound examination, both 2D and 3D. We performed a systematic literature review. Six databases were systematically searched. The results highlight how concerns related to beneficence, informed consent, and autonomy are mainly related to routine use of prenatal ultrasound in (...) the clinical context, while considerations linked to overmedicalization of pregnancy, discrimination, and fetal ontology were often reported in relation to the impact ultrasound is having on medicine and society. Ethical issues in the context of pre-abortion ultrasound, obstetric practices in low-income settings, and keepsake ultrasound imaging were also greatly discussed. Since prenatal ultrasound practices critically impact pregnant people’s autonomy and their role within pregnancy, we conclude that information providing strategies should be developed to appropriately inform pregnant people about the nature, purpose, risks, and choices revolving around prenatal ultrasound. In addition, as it is becoming increasingly difficult to separate the social and clinical dimensions of prenatal ultrasound, future research should focus on examining if and how such dimensions should be reconciled. (shrink)

International guidelines recommend that prenatal screening for fetal abnormalities should only be offered within a non-directive framework aimed at enabling women in making meaningful reproductive choices. Whilst this position is widely endorsed, developments in cell-free fetal DNA based Non-Invasive Prenatal Testing are now raising questions about its continued suitability for guiding screening policy and practice. This issue is most apparent within debates on the scope of the screening offer. Implied by the aim of enabling (...) meaningful reproductive choices is the idea that screening services should support women in accessing prenatal tests that best enable them to realize the types of reproductive choice that they find important. However, beyond whatever options meet the quality standards required for facilitating an informed decision, the remaining criteria of facilitating autonomous choice is strictly non-directive. As a result, policy makers receive little indication prior to consultation with each individual woman, about what conditions should be prioritized during the offer of screening. In this paper we try to address this issue by using the capabilities approach to further specify the non-directive aim of enabling meaningful reproductive choice. The resulting framework is then used to assess the relative importance of offering prenatal screening where concerning different types of genetic condition. We conclude that greater priority may be ascribed to offering prenatal screening for conditions that more significantly diminish a woman’s central capabilities. It follows that serious congenital and earlier-onset conditions are more likely to fulfill these criteria. (shrink)

In the near future developments in non-invasive prenatal testing may soon provide couples with the opportunity to test for and diagnose a much broader range of heritable and congenital conditions than has previously been possible. Inevitably, this has prompted much ethical debate on the possible implications of NIPT for providing couples with opportunities for reproductive choice by way of routine prenatal screening. In view of the possibility to test for a significantly broader range of genetic conditions (...) with NIPT, the European Society of Human Genetics and American Society of Human Genetics recommend that, pending further debate, prenatal screening for reproductive choice should only be offered where concerning serious congenital conditions and childhood disorders. In support of this recommendation, the ESHG and ASHG discuss a number of ethical issues on which they prompt further debate: the informational privacy of the future child, the trivialization of abortion, the risk of information overload, and issues of distributive justice. This paper responds to this call with further reflection on each ethical issue and how it relates to the moral justification of providing couples with opportunities for meaningful reproductive choice. The paper concludes that whilst there may be good reasons for qualifying the scope of any unsolicited prenatal screening offer to serious congenital conditions and childhood disorders, if prenatal screening is justified for providing couples with opportunities for meaningful reproductive choice, then health services may have obligations to empower couples with the same opportunity where concerning other conditions. (shrink)

In the debate surrounding the introduction of non-invasive prenatal testing in prenatal screening programmes, the concept of routinisation is often used to refer to concerns and potential negative consequences of the test. A literature analysis shows that routinisation has many different meanings, which can be distinguished in three major versions of the concept. Each of these versions comprises several inter-related fears and concerns regarding prenatal screening and particularly regarding NIPT in three areas: informed choice, (...) freedom to choose and consequences for people with a disability. Three of the strongest arguments raised under the flag of routinisation are assessed for their validity: the threat that NIPT poses to informed choice, the potential increase in uptake of first-trimester prenatal screening and its consequences for social pressure to participate in screening or terminate affected pregnancies, and the negative consequences for disabled people. These routinisation arguments lack empirical or normative ground. However, the results of this analysis do not imply that no attention should be paid to possible problems surrounding the introduction of NIPT. At least two problems remain and should be addressed: there should be an ongoing debate about the requirements of informed choice, particularly related to an expanded scope of prenatal screening. Also, reproductive autonomy can only be achieved when expecting parents’ options are variegated, real and valuable, so that they can continue to choose whether or not to screen or to terminate a pregnancy. (shrink)

International guidelines recommend that prenatal screening for fetal abnormalities should only be offered within a non-directive framework aimed at enabling women in making meaningful reproductive choices. Whilst this position is widely endorsed, developments in cell-free fetal DNA based Non-Invasive Prenatal Testing are now raising questions about its continued suitability for guiding screening policy and practice. This issue is most apparent within debates on the scope of the screening offer. Implied by the aim of enabling (...) meaningful reproductive choices is the idea that screening services should support women in accessing prenatal tests that best enable them to realize the types of reproductive choice that they find important. However, beyond whatever options meet the quality standards required for facilitating an informed decision, the remaining criteria of facilitating autonomous choice is strictly non-directive. As a result, policy makers receive little indication prior to consultation with each individual woman, about what conditions should be prioritized during the offer of screening. In this paper we try to address this issue by using the capabilities approach to further specify the non-directive aim of enabling meaningful reproductive choice. The resulting framework is then used to assess the relative importance of offering prenatal screening where concerning different types of genetic condition. We conclude that greater priority may be ascribed to offering prenatal screening for conditions that more significantly diminish a woman’s central capabilities. It follows that serious congenital and earlier-onset conditions are more likely to fulfill these criteria. (shrink)

An enduring ethical dispute accompanies prenatal screening and testing (PST) technologies. This ethical debate focuses on notions of reproductive choice. On one side of the dispute are those who have supported PST as a way to empower women’s reproductive choice, while on the other side are those who argue that PST, particularly when made a routine part of prenatal care, limits deliberate choice. Empirical research does not resolve this ethical debate with evidence both of women for whom (...) PST enhances their choices but also persistent evidence of recurrent problems between PST and women’s autonomous decision-making. While there have been attempts to remove challenges to reproductive choice, it has been argued that these challenges cannot be removed entirely. In this paper I provide a historical review of PST technologies’ development and in doing so provide a detailed insight into the root causes of this tension between the opposing sides of this debate. This historical account provides evidence that those who championed the early use of these technologies did so in order to achieve a number of wholly different goals other than women’s choice and empowerment. These different aims focus on scientific discovery and eugenic goals and, I argue, areirreconcilablewith women’s choice and empowerment. It thus may not be surprising that the resulting practice of PST continues to resist compatibility with women’s choice and empowerment. Ultimately, by understanding the historical foundations of PST we can more effectively assess how toreconcilewomen’s reproductive autonomy with routine prenatal screening. (shrink)

Norway’s liberal abortion law allows for abortion on social indications, yet access to screening for fetal abnormalities is restricted. Norwegian regulation of, and public discourse about prenatal screening and diagnosis has been exceptional. In this study, we wanted to investigate whether the exceptional regulation is mirrored in public attitudes. An electronic questionnaire with 11 propositions about prenatal screening and diagnosis was completed by 1617 Norwegian adults (response rate 8.5%). A majority of respondents supports increased access (...) to prenatal screening with ultrasound (60%) and/or full genome sequencing of fetal DNA (55%) available for all pregnant women. Significant minorities indicate, however, that a public offer of prenatal screening for all pregnant women would signal that people with Down syndrome are unwanted (46%) or could be criticized for contributing to a ‘sorting society’ (48%). Results indicate deeper ambivalences and a cultural sensitivity to the ethical challenges of prenatal screening and subsequent abortions. The specific diagnosis of Down syndrome and the fear of becoming a ‘sorting society’ which sorts human life due to diagnoses, appear to play prominent roles in citizen deliberations. The low response rate means that a non-response bias cannot be excluded, yet reasons why results are still likely to be of value are discussed. (shrink)

Today, French public debate and bioethics research reflect an ongoing controversy about eugenics. The field of reproductive medicine is often targeted as pre-implantation genetic diagnosis (PGD), prenatal diagnosis, and prenatal detection are accused of drifting towards eugenics or being driven by eugenics considerations. This article aims at understanding why the charge against eugenics came at the forefront of the ethical debate. Above all, it aims at showing that the charge against prenatal diagnosis is groundless. The point (...) of view presented in this article has been elaborated jointly by a geneticist and a philosopher. Besides a survey of the medical, bioethical, philosophical and social sciences literature on the topic, the methodology is founded on a joint analysis of geneticist’s various consults. Evidence from office visits demonstrated that prenatal diagnosis leads to case-by-case decisions. As we have suggested, this conclusion does not mean that prenatal diagnosis is devoid of ethical issues, and we have identified at least two. The first is related to the evaluation of a decision to abort. The second line of ethical questions arises from the fact that the claim for “normality” hardly hides normative and ambiguous views about disability. As a conclusion, ethical dilemmas keep being noticeable in the field of reproductive medicine and genetic counselling, but an enquiry about eugenic tendencies probably does not allow us to understand them in the proper way. (shrink)

Bowman-Smart et al. (2023) argue for a framework to examine the ethical issues associated with genetic screening for non-medical traits in the context of noninvasive prenatal testing (NIPT). Such s...

The routinization of prenatal diagnosis is the source of bioethical and policy debates regarding choice, autonomy, access, and protection. To understand these debates in the context of cultural diversity and moral pluralism, we compare Israel and Germany, focusing on two recent repro-genetic “hot spots” of such policy-making at the beginning of life: pre-implantation genetic diagnosis and non-invasive prenatal genetic testing, two cutting-edge repro-genetic technologies that are regulated and viewed very differently in Germany and Israel, reflecting different (...) medicolegal policies as well as public and bioethical considerations. First, we compare policy-making in the context of PGD for HLA typing, used to create sibling donors, approved in Israel under specific conditions while prohibited in Germany. Second, we compare policy-making in the context of NIPT, which came under fire in Germany, while in Israel there has been little public debate about it. Both countries justify their contrasting policies as reflecting a concern for the well-being and care of the embryo/child, thus highlighting different concepts of embryo/child protection, autonomy, family relations, and the impact of religion and history on the promotion/protection of life. We use the juxtaposition of PGD and NIPT to highlight some inconsistencies in policies concerning the protection of extra- and intra-corporeal embryos. We conclude by drawing on the comparison to show how national variations exist alongside co-evolution. (shrink)

Empirical data can be an extremely powerful and influential tool in bioethical research. However, when researchers or policy makers look for answers to ethical questions by engaging with empirical research, there can be a tendency (conscious or unconscious) to shape, report, and use empirical research in a way that confirms their own preferred ethical conclusions. This skewing effect - what we call ‘normative bias’ - is often so subtle it falls short of clear misconduct and thus can be difficult to (...) call out. However, we argue that this subtle influence of bias has the potential to significantly influence debate and policy around highly sensitive ethical issues and must be guarded against. In this paper we share the lessons we have learned through a journey of self-reflection around the effect that normative bias can have when reporting on and referring to empirical data relating to ethical issues. We use a variety of papers from our area of the ethics of routine prenatal screening to illustrate these subtle but often powerfully distorting effects of bias. Our aim in doing so is not to criticise the work of others, as we recognise our own normative bias, but to improve awareness of this issue, remind the need for reflexivity to guard against our own biases, and introduce a new criterion - the idea of a ‘limitation prominence assessment’ - that can work as a practical way to evaluate the seriousness of the limitations of an empirical study and thus, the risks of the study being misread or misinterpreted through superficial reading. (shrink)

Probably the main purpose of reproductive technologies is to enable people who choose to do so to avoid the birth of a baby with a disabling condition. However the conditions women want information about and the ‘price’ they are willing to pay for obtaining that information vary enormously. Individual women have to arrive at their own prenatal testing choices by ‘trading off’ means and ends in order to resolve the dilemmas facing them. We know very little about how individuals (...) make these trade-offs, so it is difficult to predict how new technologies will affect their choices and preferences. Uptake decisions can be expected to change, especially in the group of women who now are put off by some aspect of the current screening approach, where the avoidance of miscarriage risk may have provided a kind of ‘psychological shelter’, protecting a lot of people from having to make other decisions. Technologies such as Pre-implantation Genetic Diagnosis may remove a second ‘psychological shelter’ because they offer the means of avoiding the birth of an affected child without terminating a pregnancy. Even if new technologies will make some decisions easier in terms of their cognitive demands, they will also create new dilemmas and decision making will not necessarily become less stressful in emotional terms. Key challenges concern information and decision-making. (shrink)

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)