Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development—protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects (...) are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or ‘work’, the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context. (shrink)

: Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: regulatory oversight, confidentiality and privacy, informed consent, availability of drugs, access, and clinicians' changing responsibilities in the era of (...) pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them. (shrink)

The genetic component of variations in human responses to pharmacological agents is called pharmacogenetics while the molecular basis for these variations are most often identified as pharmacogenomics. Pharmacogenomics as a field of scientific endeavor is so new that in the scientific literature the two terms are often used interchangeably. In fact, the search for new drugs at the molecular level start with the identification of variations in DNA sequences whose products produce alterations in the amino acid structure of the (...) active portion of a protein which are then identified with the clinical disorder in question. This process is just the reverse of standard pharmaceutical approaches which begin with exploration of the physiological and potentially the biochemical basis of the specific disorder under study. The completion of the first draft of the human genome in the first months of the new millenium has increased expectations that molecular genetic approaches to drug disovery and development will significantly shorten the time-frame of new drug testing, significantly reduce the level of adverse events and anable the design of drugs to treat those with unique disorders.Based on such rosy expectations and the potential economic opportunities afforded by those who obtain such patents, there has been a rush of patent applications both in the United States and in Europe by private industry and university laboratories conducting genomic research to secure the rights to specific DNA sequences and federal agencies attempting to place the control of such information in the public domaine. This paper will document and discuss from a historic prospective the public policy and bioethical issues associated with the availability of patents for drug development. (shrink)

This paper discusses the link between pharmacogenetics and race, and the global justice issues that the introduction of pharmacogenetics in pharmaceutical research and clinical practice will raise. First, it briefly outlines the likely impact of pharmacogenetics on pharmaceutical research and clinical practice within the next five to ten years and then explores the link between pharmacogenetic traits and ‘race’. It is shown that any link between apparent race and pharmacogenetics is problematic and that race cannot be (...) used as a proxy for pharmacogenetic knowledge. The final section considers the implications of the development of pharmacogenetics for health care systems in low‐ and middle‐income countries. (shrink)

Pharmacogenetics is the study of inherited variations in drug response Pharmacogenetics uses the techniques of pharmacology, population genetics, biochemical genetics and, most recently, molecular biology, to study the biological basis for individual variation in therapeutic response and in the occurrence of adverse reactions to medications. Most pharmacogenetic experiments deal with inherited differences in drug metabolism. The discussion here will review inherited variation in the activity of thiopurine methyltransferase, an enzyme that catalyzes the methyl conjugation of an important group (...) of drugs, the thiopurines. (shrink)

The genetic component of variations in human responses to pharmacological agents is called pharmacogenetics while the molecular basis for these variations are most often identified as pharmacogenomics. Pharmacogenomics as a field of scientific endeavor is so new that in the scientific literature the two terms are often used interchangeably. In fact, the search for new drugs at the molecular level start with the identification of variations in DNA sequences whose products produce alterations in the amino acid structure of the (...) active portion of a protein which are then identified with the clinical disorder in question. This process is just the reverse of standard pharmaceutical approaches which begin with exploration of the physiological and potentially the biochemical basis of the specific disorder under study. The completion of the first draft of the human genome in the first months of the new millenium has increased expectations that molecular genetic approaches to drug disovery and development will significantly shorten the time-frame of new drug testing, significantly reduce the level of adverse events and anable the design of drugs to treat those with unique disorders.Based on such rosy expectations and the potential economic opportunities afforded by those who obtain such patents, there has been a rush of patent applications both in the United States and in Europe by private industry and university laboratories conducting genomic research to secure the rights to specific DNA sequences and federal agencies attempting to place the control of such information in the public domaine. This paper will document and discuss from a historic prospective the public policy and bioethical issues associated with the availability of patents for drug development. (shrink)

Uncertainty for policy makers is not new but the pressure to make decisions under conditions of uncertainty is perhaps greater than ever. The arrival of new scientific developments such as pharmacogenetics offers potentially great benefits . They have passionate supporters as well as doubters. The evidence is often extensive but unclear and policy makers may find themselves under pressure to make decisions before they feel that the evidence is compelling.The UK is particularly well placed to play a leading role (...) in the development of pharmacogenetics and is equally well placed to derive the benefits to both health and wealth that could flow from this. However, the uncertainties threaten to overwhelm the capacity of policy makers to act effectively. The uncertainties are both about the context within which the science and delivery of pharmacogentics is being developed and about the interests that could be served. This paper maps these uncertainties and concludes with some suggestions, drawing on deliberative democracy and futures thinking, as to how policy makers might manage the tensions and dilemmas they face by moving from an unstable, emergent policy arena to a more stable one. (shrink)

ABSTRACT Numerous benefits for patients have been predicted if prescribing decisions were routinely accompanied by pharmacogenetic testing. So far, little attention has been paid to the possibility that the routine application of this new technology could result in considerable harm to patients. This article emphasises that pharmacogenetic testing shares both the opportunities and the pitfalls with ‘conventional’ disease‐genetic testing. It demonstrates that performing pharmacogenetic tests as well as interpreting the results are extraordinarily complex issues requiring a high level of expertise. (...) It further argues that pharmacogenetic testing can have a huge impact on clinical decisions and may influence the therapeutic strategy as well as the clinical monitoring of a patient. This view challenges the predominant paradigm that pharmacogenetic testing will predict patients’ responses to medicines, but that it will not provide any other significant disease‐specific predictive information about the patient or family members. The article also questions published proposals to reduce the consent procedure for pharmacogenetic testing to a simple statement that the physician wishes to test a sample of the patient's DNA to see if a drug will be safe or whether it will work, and presents an alternative model that is better suited to protect patients’ interests and to obtain meaningful informed consent. The paper concludes by outlining conditions for the application of pharmacogenetic testing in clinical practice in a way that can make full use of its potential benefits while minimising possible harm to patients and their families. (shrink)

Pharmacogenetics and pharmacogenomics are related facets of cutting edge therapeutic research in a field that relates pharmacological properties to the genetic characteristics of human beings. An optimistic interpretation suggests that “One-Size-Fits-All” therapeutics, whose effects can only be predicted in probabilistic terms, will give way eventually to individual tailor-made therapies with entirely predictable properties in each patient. Yet the concept of anticipating individual pharmacotherapeutic response appears to disregard some of the fundamental limitations of causal understanding in the biological world of (...) structure–action relationships. It is not simply a problem of confronting complexity – which might be overcome in time with advances in biotechnology and computing power – but the inescapable paradox of the genetic characteristics of individuals within the human species. The aleatory process of evolution ensures that with the exception of monozygotic twins, every human being is genetically unique. At the same time there appears to be more in common than divides. Pharmacogenomics provides a climate in which to explore and better understand the variable causal relationships between genetic element, protein and therapeutic or toxic actions, but can only do so in abstraction. Thus␣predictive power may be enhanced but is ultimately constrained by insuperable probabilistic considerations. (shrink)

Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development—protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects (...) are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or ‘work’, the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context. (shrink)

Pharmacogenetics is an emerging biotechnology concerned with understanding the genetic basis of drug response, and promises to transform the development, marketing and prescription of medicines. This paper is concerned with analysing the move towards segmented drug markets, which is implicit in the commercial development of pharmacogenetics. It is claimed that in future who gets a particular drug will be determined by their genetic make up. Drawing on ideas from the sociology of expectations we examine how pharmaceutical and biotechnology (...) companies are constructing, responding to and realising particular ‘visions’ or expectations of pharmacogenetics and market stratification. We argue that the process of market segmentation remains uncertain, but that the outcome will be fashioned according to the convergence and divergence of the interests of key commercial actors. Qualitative data based both on interviews with industry executives and company documentation will be used to explore how different groups of companies are developing pharmacogenetics in distinct ways, and what consequences these different pathways might have for both clinical practice and health policy. In particular, the analysis will show a convergence of interests between biotechnology and pharmaceutical companies for creating segmented markets for new drugs, but a divergence of interest in segmenting established markets. Whilst biotechnology firms have a strong incentive to innovate, the pharmaceutical industry has no commercial interest in segmenting markets for existing products. This has important implications, as many of the claimed public health benefits of pharmacogenetics will derive from changing the prescribing of existing medicines. One significant implication of this is that biotechnology companies who wish to apply pharmacogenetics to existing medicines will have to explore an alternative convergence of interests with healthcare payers and providers . Healthcare providers may have a strong incentive to use pharmacogenetics to make the prescribing of existing medicine more cost-effective. However, we conclude by suggesting that a question mark hangs over their ability to provide the necessary economic and structural resources to bring such a vision to fruition. (shrink)

ABSTRACT Pharmacogenetics is a rapidly expanding area of research exploring the relationship between inter‐individual genetic variation and drug response, with the goal of developing genetically optimised therapies. Slippery slope arguments claim that a particular action should be rejected (or supported) because it might be the first step onto a slippery slope leading to undesirable (or desirable) consequences. In this article, several slippery slope arguments relevant to the context of pharmacogenetics are evaluated under consideration of underlying reasons for their (...) popularity. The author concludes that although the examined arguments are unconvincing as slippery slope arguments, they do matter in this context. While positive slippery slope arguments serve as a driving force to fuel the development of pharmacogenetics, their negative counterparts play an important role to sensitise policy makers and the public to potential problems. (shrink)

With the human genome mapped, and with the mapping of more than one hundred animal genomes in progress, the amount of genetic data available is increasing exponentially. This exponential increase in data is having an immediate impact on the process of drug development. By using techniques of information technology to manipulate data regarding the genes, proteins, and biochemical pathways associated with various diseases, scientists are beginning to be able to design drugs in a systematic fashion. In the context of any (...) given disease, scientists look to see whether a gene, a protein for which the gene codes, or another protein in the relevant biochemical pathway could be the “target” biological molecule, the “knocking out” of which would halt or slow the disease's progression. Once a target molecule has been identified and characterized structurally, drug therapies that would be likely to knock out this target can be identified and tested systematically. The merger of information technology and genetic technology has changed the process of pharmaceutical development so much that a new term—bioinformatics—has been coined to describe this new approach to such development. (shrink)

Since the inception of the Human Genome Project, human genetics has frequently been conducted through big science projects, combining academic, state and industrial methods, interests and resources. The legitimacy of such projects has been linked to national prestige and images of the nation, the purity of scientific endeavour, the entrepreneurial spirit, medical progress and the public health. A key complication in these discourses is that large-scale genetic research has yet to show major results when considered in terms of the objectives (...) used to legitimate investment and social support for these projects. The main area showing promise at present is the developing field of pharmacogenetics, which is now attracting major industry and government investment. Sociological, ethical and philosophical study of human genetic sample-based research and pharmacogenetics has developed in parallel with inquiry in the biological and biomedical sciences. This paper introduces a symposium on the ethical and social aspects of this field of biomedical research. (shrink)

The existing EELS literature has usefully identified the scope of ethical issues posed by pharmacogenetic and pharmacogenomic research. The time has come for in-depth examination of particular ethical issues. The involvement of racial and ethnic communities in pharmacogenetic and pharmacogenomic research is contentious precisely because it touches upon the science and politics of studying racial and ethnic difference. To date, the ethics literature has not seriously taken account of the fact that such research impinges upon the interests of communities, and (...) that taking such interests seriously requires that we both protect and empower communities in research. We propose a framework that rests upon the recognition that communities are heterogeneous human associations and differing policies are appropriate for differing communities. Community consent and consultation and community consultation alone are neither appropriate nor required for all pharmacogenetic and pharmacogenomic research. Rather, application of these policy protections must take into account particulars of both planned research and the communities involved. (shrink)

In September this year the Nuffield Council on Bioethics held a meeting to disclose and discuss the main findings of their newly published report on the ethical issues associated with developments in pharmacogenetics research. The basics of pharmacogenetics science is briefly outlined, and then the extent to which the report was successful in addressing the attendant social, ethical, and policy implications of pharmacogenetics research is evaluated.

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, ‘traditional’ genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice.This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics (...) and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer’s disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice. (shrink)

Current controversy over whether the Office of Management and Budget system of racial and ethnic classification should be used in pharmacogenetics research as suggested by the U.S. Federal Drug Administration has been couched in terms of realist-social constructionist debates on race. The assumptions both parties to these debates share instead need to be relinquished—specifically, dichotomies between the social and scientific and what is descriptive and evaluative/normative. This paper defends a pragmatic approach to the question of the appropriateness of the (...) OMB group categories in pharmacogenetics research, an approach that is local and context-specific rather than global, incorporates practical and ethical as well as theoretical dimensions, and recognizes intersections of the social and the biological in the constitution of group categories. (shrink)

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, ‘traditional’ genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. -/- This paper presents results from interviews with clinicians (...) who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer’s disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice. -/- . (shrink)

Since the inception of the Human Genome Project, human genetics has frequently been conducted through big science projects, combining academic, state and industrial methods, interests and resources. The legitimacy of such projects has been linked to national prestige and images of the nation, the purity of scientific endeavour, the entrepreneurial spirit, medical progress and the public health. A key complication in these discourses is that large-scale genetic research has yet to show major results when considered in terms of the objectives (...) used to legitimate investment and social support for these projects. The main area showing promise at present is the developing field of pharmacogenetics, which is now attracting major industry and government investment. Sociological, ethical and philosophical study of human genetic sample-based research and pharmacogenetics has developed in parallel with inquiry in the biological and biomedical sciences. This paper introduces a symposium on the ethical and social aspects of this field of biomedical research. (shrink)

This study is the first to examine the understandings that participants have of the consent process in a pharmacogenetic trial of anti-depressant medication.

Research Ethics, Volume 18, Issue 3, Page 193-209, July 2022. This study aimed to explore experiences and practices of key research team members in obtaining informed consent for pharmacogenetics research and to identify the approaches used for enhancing understanding during the consenting process. Data collection involved 15 qualitative, in-depth interviews with key researchers who were involved in obtaining informed consent from HIV infected individuals in Uganda for participation in pharmacogenetic clinical trials. The study explored two prominent themes: approaches used (...) to convey information and enhance research participants’ understanding and challenges faced during the consenting process. Several barriers and facilitators for obtaining consent were identified. Innovative and potentially effective consenting strategies were identified in this study that should be studied and independently verified. (shrink)

This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non‐validated or hypothesis‐generating). There is, however, a trend for research participants to be (...) permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico‐legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer ‘Points‐to‐Consider’ regarding returning research results in the context of drug development trials based on their knowledge and experience. These considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit‐to‐risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies. (shrink)

ABSTRACT This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non‐validated or hypothesis‐generating). There is, however, a trend for research participants to (...) be permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico‐legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer ‘Points‐to‐Consider’ regarding returning research results in the context of drug development trials based on their knowledge and experience. These considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit‐to‐risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies. (shrink)

Pharmacogenetics and pharmacogenomics are related facets of cutting edge therapeutic research in a field that relates pharmacological properties to the genetic characteristics of human beings. An optimistic interpretation suggests that “One-Size-Fits-All” therapeutics, whose effects can only be predicted in probabilistic terms, will give way eventually to individual tailor-made therapies with entirely predictable properties in each patient. Yet the concept of anticipating individual pharmacotherapeutic response appears to disregard some of the fundamental limitations of causal understanding in the biological world of (...) structure–action relationships. It is not simply a problem of confronting complexity – which might be overcome in time with advances in biotechnology and computing power – but the inescapable paradox of the genetic characteristics of individuals within the human species. The aleatory process of evolution ensures that with the exception of monozygotic twins, every human being is genetically unique. At the same time there appears to be more in common than divides. Pharmacogenomics provides a climate in which to explore and better understand the variable causal relationships between genetic element, protein and therapeutic or toxic actions, but can only do so in abstraction. Thus␣predictive power may be enhanced but is ultimately constrained by insuperable probabilistic considerations. (shrink)

Even in the increasingly individualized American medical system, advocates of 'personalized medicine' claim that healthcare isn't individualized enough. With the additional glamour of new biotechnologies such as genetic testing and pharmacogenetics behind it, 'Me Medicine'-- personalized or stratified medicine-- appears to its advocates as the inevitable and desirable way of the future. Drawing on an extensive evidence base, this book examines whether these claims are justified. It goes on to examine an alternative tradition rooted in communitarian ideals, that of (...) the common good as a goal in medicine. (shrink)

Genetic testing has historically been performed in the context of chronic disease and cancer diagnostics. The timelines for these tests are typically measured in days or weeks, rather than in minutes. As such, the concept that genetic information might be generated and then used to alter management in the acute setting has, thus far, not been feasible. However, recent advances in genetic technologies have the potential to allow genetic information to be generated significantly quicker. The m.1555A>G genetic variant is present (...) in one in 500 individuals and predisposes to profound hearing loss following the administration of aminoglycoside antibiotics. These antibiotics are used frequently in cases of neonatal sepsis and it is estimated that approximately 180 neonates in the UK are at risk of antibiotic induced hearing loss each year because of this genetic change. Knowledge of this variant in the acute setting would allow clinicians to prescribe alternative antibiotics. The Pharmacogenetics to Avoid Loss of Hearing study will implement a genetic point of care test for the m.1555A>G variant within two major UK based neonatal intensive care units. This represents the first trial of a genetic POCT aimed at altering management in the acute setting. This round table discussion outlines the novel ethical issues faced in the development of this trial and the legal barriers to implementation. We ask five stakeholders to provide their opinions on this trial and their perspectives on the concept of genetic testing in the acute setting.Trial registration numberISRCTN-13704894. (shrink)

ABSTRACT A key selling point of pharmacogenetics is the genetic stratification of either patients or diseases in order to target the prescribing of medicine. The hope is that genetically ‘tailored’ medicines will replace the current ‘one‐size‐fits‐all’ paradigm of drug development and usage. This paper is concerned with the relationship between difference and justice in the use of pharmacogenetics. This new technology, which facilitates the identification and use of difference, has, we shall argue, the potential to lead to injustice (...) either by the inappropriate use of difference or through the inappropriate failure to use difference. We build on empirical data from a detailed study of the range of options for the development of pharmacogenetics to present a consideration of the ethical issues that surround patient and disease stratification. In it we explore the ways in which the use of pharmacogenetics may lead to the creation of new, genetically stratified, forms of difference and new forms of injustice based on these divisions. We also examine the ways in which existing forms of difference and social stratification may interact with the use of pharmacogenetics. In conclusion, we suggest how an understanding of these ethical issues could usefully inform future policy discussions. (shrink)

As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed (...) the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed. (shrink)

In this response article, we challenge a core assumption that lies at the centre of a round table discussion regarding the Pharmacogenetics to Avoid Loss of Hearing trial. The round table regards a genetic test for a variant that increases the risk of deafness if a carrier is given the antibiotic gentamicin. The idea is that rapid testing can identify neonates at risk, providing an opportunity to prevent giving an antibiotic that might cause deafness. We challenge the assumption that (...) a positive test unequivocally guides antibiotic choice because, aside from the risk of deafness, all antibiotics for neonatal sepsis are equivalent. We argue that this assumption is faulty and has particularly troubling moral consequences. We claim that giving an alternative to gentamicin is potentially providing inferior treatment and thereby may increase the risk of death. Parents and doctors are faced with a terrible choice as a result of positive point-of-care testing : give gold-standard treatment and risk deafness or give second line care and risk death. While we do not indicate an answer to this choice, what we do argue is that such a deep and difficult choice is one that may make parents wish genetic testing was never undertaken, and therefore, contra some authors in the round table, provides a reason to gain specific consent for POCT. (shrink)

Sex is a fundamentally important biological variable. Recent years have seen significant progress in the integration of sex in many aspects of basic and clinical research, including analyses of sex differences in brain function. Significant advances in the technology available for studying the endocrine and nervous systems are now coupled with a more sophisticated awareness of the interconnections of these two communication systems of the body. A thorough understanding of the current knowledge, conceptual approaches, methodological capabilities, and challenges is a (...) prerequisite to continued progress in research and therapeutics in this interdisciplinary area. Sex Differences in the Brain provides scientists with the basic tools for investigating sex differences in brain and behavior and insight into areas where important progress in understanding physiologically relevant sex differences has already been made. This book was edited and co-authored by members of the Isis Fund Network on Sex, Gender, Drugs and the Brain, sponsored by the Society for Womens Health Research. The book is arranged in three parts. The first part of the book introduces the study of sex differences in the brain, with an overview of how the brain, stress systems, and pharmacogenetics differ in males and females and how this information is important for the study of behavior and neurobiology of both genders. The second part presents examples of sex differences in neurobiology and behavior from both basic and clinical research perspectives, covering both humans and nonhuman animals. The final part discusses sex differences in the neurobiology of disease and neurological disorders. For interested individuals as well as those who are considering conducting research at the intersections of endocrinology, neuroscience, and other areas of biomedicine, the study of sex differences offers exciting and challenging questions and perspectives. This book is intended as a guide and resource for clinicians, scientists, and students. (shrink)

Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out (...) from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science. (shrink)

This article explores the way in which social explanations underpin the names of particular disciplines. Taking the example of pharmacogenomics, it shows how this term has been constructed since it appeared in 1997, the differences and similarities between it and its precursor, pharmacogenetics, and the way in which commercial interests underpin this new term. Drawing on the idea of visions and the sociology of expectation, the article shows how different actors compete to have their preferred definitions of the term (...) accepted by the world at large. (shrink)

Recent scientific developments, in particular advances in pharmacogenetics and molecular genetics, have given rise to numerous predictive procedures for detecting predispositions to diseases in patients. This knowledge, however, does not necessarily promise benign results for either patients or health care professionals. The aim of this volume is to analyse issues related to prediction and prognosis as a burgeoning field of medicine, which is revolutionizing the way we understand and approach diagnosis and treatment. Combining epistemic and ethical reflection with medical (...) expertise on contemporary practice and research, an interdisciplinary group of international experts critically examine anticipatory medicine from various perspectives, including history of medicine, bioethics, theories of science, and health economics. The highly complex issues involved in medical prediction call for a far-reaching debate on the value and scope of foreknowledge. For example, which responsibilities and burdens arise when still healthy people learn of their predisposition to diseases? How should health care insurance reflect risky life styles? Is the increasing medicalization of life connected with prevention ethically sustainable and financially possible in the developing world? These and other related issues are the subject of this timely and important book, which not only serves as an introduction to the area, but also proposes many feasible solutions to the problems outlined. (shrink)

Las biotecnologías son ciencias destinadas a incidir en manera profunda en la sociedad. El alcance de los cambios que a través de ellas será posible realizar es notable, pero sobre todo se aleja de las ciencias de ingeniería, de las alimentarias, de las médicas. La bioética está decididamente llamada a acoger el reto representado por las biotecnologías. La presente contribución parte precisamente de aquí: captar los aspectos característicos y peculiares de algunas de las posibles aplicaciones biotecnológicas para encuadrar la singularidad (...) de las problemáticas bioéticas que de estas aplicaciones pueden derivar con el fin de leer tales contribuciones a la luz del valor al cual se refieren y por el cual están pensadas: la persona En lo específico, los autores se detienen en tres específicas aplicaciones biotecnológicas que representan sectores cuyas potencialidades preanuncian grandes promesas y, en ciertos aspectos, algunos retos verdaderamente cautivadores; en particular: los OGM, las nanotecnologías y la farmacogenética, temas en diversos modos considerados en la revista en el curso de los años.Biotechnologies, the use of living organisms or their products to modify human environment, are flourishing very rapidly. They cover many fields: from engineering science, to food, to medicine. Bioethics is therefore called to face the challenge given by biotechnologies. The present contribution takes advantage from this: it catches all the scientific peculiarities showed by these technologies and their application to outline the peculiarities of their ethical issues and to read them in the light of their end: the human persono In fact, thanks to them, it will be possible to realize many transformations within the society. In particular, the authors evaluate three main aspects of biotechnologies OGM, Nanotechnologies and pharmacogenetics, topics covered in the journal on several occasions over the years. (shrink)

Genetic knowledge is a civil right and a civil obligation. New genetic knowledge in individual health risk prediction and prevention and new pharmacogenetic opportunities for developing more efficacious individualized drugs broaden human and civil rights for better health and health care. Public health policy has yet to develop and provide programs in genetic information and consultation together with other health risk information and health literacy education. Data availability and genetic knowledge will make citizens more competent partners in health risk management. (...) As with all information, abuse and manipulation of genetic information cannot be excluded; but health education as an essential part of public health services will empower citizens to better care for their own and their families health. Existing cultural and ethical principles, laws and regulations need to be reviewed and modified in order to prevent and fight illegal or immoral use of genetic information. The promotion of genetic knowledge allows for a new model of social contract as health care contract between citizens, health care experts, and society. (shrink)

The ongoing debate about the FDA approval of BiDil in 2005 demonstrates how the first racially/ethnically licensed drug is entangled in both Utopian and dystopian future visions about the continued saliency of race/ethnicity in science and medicine. Drawing on the sociology of expectations, this paper analyzes how scientists in the field of pharmacogenetics are constructing certain visions of the future with respect to the use of social categories of race/ethnicity and the impact of high-throughput genotyping technologies that promise to (...) transform scientific practices. (shrink)

In this article ethical issues are discussed which play a role in pharmacogenetics. Developments in pharmacogenetics have a large impact on many different practices such as clinical trials, the practice of medicine and society at large. In clinical trials, questions rise regarding the exclusion of genetic subgroups that may be non- or poor-responders to the experimental drug. Also, the question is asked how pharmaceutical companies should deal with their growing knowledge about the relations between genetic variation and adverse (...) effects. Moreover, pharmacogenetics may provide disease-specific predictive information which may have a significant impact on the relations between physicians, patients and their relatives in the practice of medicine. Here, issues also arise regarding responsibility of patients and physicians for health and disease. In the society at large, the high costs of new pharmacogenetic possibilities lead to questions concerning solidarity and fair distribution on a national as well as an international level. It is concluded that in the near future, ethical research should be focused on the themes responsibility, inclusion and exclusion and global justice. (shrink)

The tobacco industry first began to promote the idea that a minority of smokers are 'genetically predisposed' to lung cancer in the 1950s. We used tobacco industry documents available as a result of litigation to investigate the role of the tobacco industry in funding the 'scientific bandwagon' described by Fujimura, in which genetics has come to dominate the cancer research agenda. From 1990-1995 inclusive, 52% of the project funding allocated by British American Tobacco's Scientific Research Group went to genetic research, (...) mainly based in universities and at one cancer charity. The largest project involved a pharmacogenetic research unit, based in a UK medical school, which was established with the help of tobacco industry PR consultants in 1988. The unit received half its project funding from the industry in 1992. Its main aim was to identify a minority of smokers who are supposedly 'genetically susceptible' to lung cancer, so that smoking cessation measures could be targeted at them. This aim was adopted and promoted by influential scientists at the US National Institutes of Health and the UK Medical Research Council in the late 1980s, in the run up to the Human Genome Project.BAT's research funds were also used to counter claims by others to have identified a unique 'genetic fingerprint' for tobacco smoke in lung cancer cells. We conclude that the tobacco industry has played a significant role in shaping research agendas, in particular, by promoting the idea that individual genome screening would be of benefit to public health. (shrink)

We inquire into the notions of ‘boundary’ and ‘cluster’ in the fields of medical genetics, pharmacogenetics, and population genetics. First we show that the two notions are not well discussed in literature. Then we propose a promising explication of them, in which we argue that clustering is always ‘property laden’, that is, fundamentally dependent on decisions about the properties to be taken into account. In particular we suggest three different kinds of properties that have a role in these decisions. (...) That is, we conclude that boundaries and clusters among humans depend on our way of considering nature. Concepts of ‘race’ and ‘ethnic group’ are discussed too, since they are the most used clusters among humans. (shrink)

This paper is concerned with analyzing transformations in the development, marketing, prescription, and access issues of pharmaceuticals, paying special attention to a variety of ethical and social aspects. A major focus of the article is on pharmacogenetics – a rapidly developing discipline which in the near future might well have a major effect on both drug development and clinical medicine.

The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to (...) patients and their families. Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account. This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results. This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees. (shrink)

We thank Parker and Wright for engaging in this roundtable debate in such a spirited way. The ‘Pharmacogenetic [test] to Avoid Loss of Hearing’ Trial is the first time a genetic point of care test has been applied in the acute neonatal setting; therefore, it is not surprising that questions have been raised which require debate, discussion and clarification. Parker and Wright misattribute several assumptions to the roundtable authors, which we would like to clarify here. Since they raise wider questions (...) about the PALOH trial itself, several of the roundtable discussants have made a joint response. (shrink)