Wim Pinxten

Ethical issues raised by whole genome sequencing

While there is ongoing discussion about the details of implementation of whole genome sequencing (WGS) and whole exome sequencing (WES), there appears to be a consensus amongst geneticists that the widespread use of these approaches is not only inevitable, but will also be beneficial [1]. However, at the present time, we are unable to anticipate the full range of uses, consequences and impact of implementing WGS and WES. Nevertheless, the already known ethical issues, both in research and in clinical practice are diverse and complex and should be addressed properly presently. Herein, we discuss the ethical aspects of WGS and WES by particularly focussing on three overlapping themes: (1) informed consent, (2) data handling, and (3) the return of results.

Barriers in the Uptake and Delivery of Preconception Care: Exploring the Views of Care Providers

Objectives To examine health care professionals’ views of their role and responsibilities in providing preconception care and identify barriers that affect the delivery and uptake of preconception care. Methods Twenty health care professionals who provide preconception care on a regular basis were interviewed using semi-structured interviews. Results We interviewed twelve community midwives, three General Practitioners, three obstetricians, one cardiologist specialized in congenital heart diseases and one gastroenterologist.We identified four barriers affecting the uptake and delivery of preconception care (PCC): (1) lack of a comprehensive preconception care program; (2) limited awareness of most future parents about the benefits of preconception care, hesitance of GP’s about the necessity and effectiveness of PCC; (3) poor coordination and organization of preconception care; (4) conflicting views of health care professionals on pregnancy, reproductive autonomy of patients and professional responsibility. Conclusion We have identified four barriers in the uptake and delivery of preconception care. Our findings support the timely implementation of a comprehensive program of PCC (already advocated by the Health Council of the Netherlands) and increasing awareness and knowledge of PCC from care providers and future parents. We emphasize the need for further research on how organizational barriers lead to suboptimal PCC and how interdisciplinary collaboration and referral can lead to optimally tailored intervention approaches.

Measuring states of pathological (un)consciousness: research dimensions, clinical applications, and ethics

Abstract Consciousness is a multidimensional construct with no widely accepted definition. Especially in pathological conditions, it is less clear what exactly is meant by (un)consciousness, how it can be reliably observed or measured. Here, we aim at (i) bringing together state of the art approaches to classification of single patients suffering from disorders of consciousness by means of motor-independent assessment of consciousness states with electrophysiology and functional neuroimaging, (ii) showing how each proposed metric translates into clinical practice and (iii) raising a discussion on the ethical aspects of consciousness measurements. We realize that when dealing with patients some issues commonly pertain to each methodology discussed here, such as the overall clinical condition, clinical heterogeneity, and diagnostic uncertainty. When predicting patients’ diagnosis, though, each method adopts a different approach to determine (a) a “gold standard” of the benchmark population upon which the metric is computed and (b) the generalization and replicability in the attempt to avoid overfitting. From an applied ethics perspective, the focus is, hence, on knowing what one is measuring and on the validity of measurements. We conclude that, when searching for consciousness in pathological conditions, confident diagnosis can be based on the use of probabilistic predictions as well as on accumulative evidence stemming from multiple non-overlapping assessments with different modalities. A framework which will regulate the application order of these techniques (balancing their availability, sensitivity, and specificity, based on underlying clinical assumptions about a patient’s conscious state), is expected to ameliorate clinical management and further inform on the critical patterns of (un)consciousness.

Content Analysis of Informed Consent for Whole Genome Sequencing Offered by Direct-to-Consumer Genetic Testing Companies

Whole exome sequencing (WES) and whole genome sequencing (WGS) have become increasingly available in the research and clinical settings and are now also being offered by direct‐to‐consumer (DTC) genetic testing (GT) companies. This offer can be perceived as amplifying the already identified concerns regarding adequacy of informed consent (IC) for both WES/WGS and the DTC GT context. We performed a qualitative content analysis of Websites of four companies offering WES/WGS DTC regarding the following elements of IC: pre‐test counseling, benefits and risks, and incidental findings (IFs). The analysis revealed concerns, including the potential lack of pre‐test counseling in three of the companies studied, missing relevant information in the risks and benefits sections, and potentially misleading information for consumers. Regarding IFs, only one company, which provides opportunistic screening, provides basic information about their management. In conclusion, some of the information (and related practices) present on the companies’ Web pages salient to the consent process are not adequate in reference to recommendations for IC for WGS or WES in the clinical context. Requisite resources should be allocated to ensure that commercial companies are offering high‐throughput sequencing under responsible conditions, including an adequate consent process.

Ethical framework for the detection, management and communication of incidental findings in imaging studies, building on an interview study of researchers’ practices and perspectives

BackgroundAs thousands of healthy research participants are being included in small and large imaging studies, it is essential that dilemmas raised by the detection of incidental findings are adequately handled. Current ethical guidance indicates that pathways for dealing with incidental findings should be in place, but does not specify what such pathways should look like. Building on an interview study of researchers’ practices and perspectives, we identified key considerations for the set-up of pathways for the detection, management and communication of incidental findings in imaging research.MethodsWe conducted an interview study with a purposive sample of researchers (n = 20) at research facilities across the Netherlands. Based on a qualitative analysis of these interviews and on existing guidelines found in the literature, we developed a prototype ethical framework, which was critically assessed and fine-tuned during a two-day international expert meeting with bioethicists and representatives from large population-based imaging studies from the United Kingdom, Germany, Sweden and Belgium (n = 14).ResultsPractices and policies for the handling of incidental findings vary strongly across the Netherlands, ranging from no review of research scans and limited feedback to research participants, to routine review of scans and the arrangement of clinical follow-up. Respondents felt that researchers do not have a duty to actively look for incidental findings, but they do have a duty to act on findings, when detected. The principle of reciprocity featured prominently in our interviews and expert meeting.ConclusionWe present an ethical framework that may guide researchers and research ethics committees in the design and/or evaluation of appropriate pathways for the handling of incidental findings in imaging studies. The framework consists of seven steps: anticipation of findings, information provision and informed consent, scan acquisition, review of scans, consultation on detected abnormalities, communication of the finding, and further clinical management and follow-up of the research participant. Each of these steps represents a key decision to be made by researchers, which should be justified not only with reference to costs and/or logistical considerations, but also with reference to researchers’ moral obligations and the principle of reciprocity.

Quality of medicines in resource-limited settings: need for ethical guidance

ABSTRACT The quality of medicines is generally adequately assured by manufacturers and regulatory authorities for well-resourced settings, while the implementation of existing quality standards is challenged in many low- and middle-income countries. This situation of multiple pharmaceutical standards raises the question whether it could ever be ethically justified to compromise on the quality assurance of medicines depending on what individuals, communities, or societies can afford. In this paper, we contend that ethically, any unjustified exceptions to medicines’ quality assurance represents a violation of the principles of beneficence and non-maleficence. Exceptions are only acceptable in exceptional and temporary circumstances, if based on a meaningful quality risk assessment, guided by a rigorous ethical framework built on the principles of independence, technical competence, transparency, and accountability. We also discuss how such exceptional and temporary circumstances should be defined/justified. Finally, we propose that empirical bioethics should acknowledge the existence of these dilemmas in public health, and help to build a normative approach to dealing with them. Ideally, an international group of experts in quality assurance/regulatory affairs and health ethicists should be set up to take up this topic and formulate a Guide to Ethical Principles of Quality Assurance of Medical Products.

Risks in a Trial of an Innovative Treatment of Duchenne Muscular Dystrophy

Studies of innovative therapies for muscular dystrophy raise unique ethical issues. The disease is currently untreatable and relentlessly progressive. A number of potentially efficacious treatments are being developed, but like all treatments, they may have unforeseen adverse effects. Nevertheless, patients and families, facing a bleak future, may be willing to take the gamble and try the treatments. Many doctors are eager to study them. But should institutional review boards approve them? This article discusses these issues and recounts the ways that one such study elicited different responses from different institutional review boards.

You don’t Grow Old on Your Own

Age is a metamorphosis (particularly physical). A competition (in infirmities, illness and length of life). The bill you pay for your life. A liberation. A job you have to do. A confused script. Involuntary house arrest. A challenge. A punishment (at least), a disaster (at worst).