Regarding the Yin and Yang of Precision Cancer- Screening and Treatment: Are We Creating a Neglected Majority?

In this commentary, we submit that the current emphasis of precision cancer screening and treatment (PCST) has been to provide and interpret the implications of "positive" screening results for those deemed to be at greatest risk for cancer or most likely to benefit from targeted treatments. This is an important, but proportionately small target group, regardless of the cancer context. Overlooked by this focus is the larger majority of those screened who receive "negative" results. We contend that for optimal dissemination of PCST, the complement of positive and negative results be viewed as an inseparable yin-yang duality with the needs of those who receive negative screening results viewed as important as those deemed to be at highest risk or derive targeted treatment benefit. We describe three areas where communication of negative PCST results warrant particular attention and research consideration: population-based family history screening, germline testing for hereditary cancer syndromes, and tumor testing for targeted cancer treatment decision-making. Without thoughtful consideration of the potential for negative results to have psychological and behavioral influences, there is a potential to create a "neglected majority". This majority may be inclined to misinterpret results, disseminate inaccurate information to family, dismiss the credibility of results, or become disillusioned with existing medical treatments.

Ethics, genetic testing, and athletic talent: children's best interests, and the right to an open (athletic) future.

In this paper we discuss the ethics of genetics-based talent identification programs in sports. We discuss the validity and reliability of the tests and the claims made by direct to consumer companies, before presenting a range of ethical issues concerning child-parent/guardian relations raised by these tests, which we frame in terms of parental/guardian duties, children's rights, and best interests. We argue that greater ethical emphasis needs to be put on the parental decision on the wellbeing on the child going forward, not on ex post justifications on the basis of good and bad consequences. Best interests decisions made by a third party seem to comprise both subjective and objective elements, but only a holistic approach can do justice to these questions by addressing the wellbeing of the child in a temporal manner and taking into account the child's perspective on its wellbeing. Such decisions must address wider questions of what a good (sports)parent ought do to help the child flourish and how to balance the future-adult focus necessary to nurture talent with the wellbeing of the child in the present. We conclude that current genetic tests for "talent" do not predict aptitude or success to any significant degree and are therefore only marginally pertinent for talent identification. Claims that go beyond current science are culpable and attempt to exploit widespread but naïve perceptions of the efficacy of genetics information to predict athletic futures. Sports physicians and health care professionals involved in sport medicine should therefore discourage the use of these tests.

Against Genetic Tests for Athletic Talent: The Primacy of the Phenotype.

New insights into the genetics of sport performance lead to new areas of application. One area is the use of genetic tests to identify athletic talent. Athletic performances involve a high number of complex phenotypical traits. Based on the ACCE model (review of Analytic and Clinical validity, Clinical utility, and Ethical, legal and social implications), a critique is offered of the lack of validity and predictive power of genetic tests for talent. Based on the ideal of children's right to an open future, a moral argument is given against such tests on children and young athletes. A possible role of genetic tests in sport is proposed in terms of identifying predisposition for injury. In meeting ACCE requirements, such tests could improve individualised injury prevention and increase athlete health. More generally, limitations of science are discussed in the identification of talent and in the understanding of complex human performance phenotypes. An alternative approach to talent identification is proposed in terms of ethically sensitive, systematic and evidence-based holistic observation over time of relevant phenotypical traits by experienced observers. Talent identification in sport should be based on the primacy of the phenotype.

That tumor you're going to get tomorrow maybe: making an informed decision.

With the recent progress in predictive medicine several problems have emerged regarding the ethical aspects of genetic testing. The role of the doctor in communicating the consequences of such testing to the patient has become more important than ever in allowing the potential patient to make an informed decision.

Prenatal screening, reproductive choice, and public health.

One widely held view of prenatal screening (PNS) is that its foremost aim is, or should be, to enable reproductive choice; this is the Pure Choice view. The article critiques this position by comparing it with an alternative: Public Health Pluralism. It is argued that there are good reasons to prefer the latter, including the following. (1) Public Health Pluralism does not, as is often supposed, render PNS more vulnerable to eugenics-objections. (2) The Pure Choice view, if followed through to its logical conclusions, may have unpalatable implications, such as extending choice well beyond health screening. (3) Any sensible version of Public Health Pluralism will be capable of taking on board the moral seriousness of abortion and will advocate, where practicable, alternative means of reducing the prevalence of disease and disability. (4) Public Health Pluralism is at least as well-equipped as the Pure Choice model to deal with autonomy and consent issues.

A new ethical landscape of prenatal testing: individualizing choice to serve autonomy and promote public health: a radical proposal.

A new landscape of prenatal testing (PNT) 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.

Prenatal screening: an ethical agenda for the near future.

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.

'A morass of considerations': exploring attitudes towards ethnicity-based haemoglobinopathy-carrier screening in primary care.

BACKGROUND: The Netherlands does not have a national haemoglobinopathy (HbP)-carrier screening programme aimed at facilitating informed reproductive choice. HbP-carrier testing for those at risk is at best offered on the basis of anaemia. Registration of ethnicity has proved controversial and may complicate the introduction of a screening programme if based on ethnicity. However, other factors may also play a role. OBJECTIVE: To explore perceived barriers and attitudes among GPs and midwives regarding the registration of ethnicity and ethnicity-based HbP-carrier screening. METHODS: Six focus groups in Dutch primary care, with a total of 37 GPs (n = 9) and midwives (n = 28) were conducted, transcribed and content analysed using Atlas-ti. RESULTS: Both GPs and midwives struggled with correctly identifying ethnicities at risk for HbP. Ethical concerns regarding privacy seemed to originate from World War II experiences, when ethnic and religious registration facilitated deportation of Jewish citizens, coupled with the political climate at the time focus groups were held. Some respondents thought the ethnicity question might undermine the relationship with their clients. Software programmes prevented GPs from registering ethnicity of patients at risk. Financial implications for patients were also a concern. Despite this, respondents seemed positive about screening and were familiar with identifying ethnicity and used this for individual patient care. CONCLUSIONS: Although health professionals are generally positive about screening, ethical, financial and practical issues surrounding ethnicity-based HbP-carrier screening need to be clarified before introducing such a programme. Primary care professionals can be targeted through professional organizations but they need national policy support.

Attitudes of general practitioners and midwives towards ethnicity-based haemoglobinopathy-carrier screening.

Haemoglobinopathies (HbP) are severe autosomal recessive disorders with high prevalence among certain ethnic groups. World Health Organisation (WHO) advises implementing screening programmes for risk groups. Research in the Netherlands has shown that general practitioners and midwives do not perceive ethnicity as a risk factor for HbP. Moreover, registration of ethnicity is a controversial societal issue, which may complicate the introduction of a national preconception or antenatal carrier screening programme. This study investigates attitudes, intention and behaviour of general practitioners and midwives towards ethnicity-based HbP-carrier screening in general. A structured questionnaire based on the Theory of Planned Behaviour was sent by mail to a random selection of 2100 general practitioners and 1800 primary care midwives. Response was 35% (midwives 44.2%; GPs 27.6%). Although 45% of respondents thought that offering a carrier test on the basis of ethnicity alone should become national policy, it is currently not carried out. The main factor explaining lack of intention towards ethnicity-based HbP-carrier screening was subjective norm, the perception that their peers do not think they should offer screening (52.2% variance explained). If ethnicity-based HbP-carrier screening would become national policy, most professionals report that they would carry this out. Most respondents favoured ethnicity registration for health purposes. As most practitioners look for role models among peers, debate among general practitioners and midwives should be encouraged when new policy is to be developed, articulating the voices of colleagues who already actively offer HbP-carrier screening. Moreover, primary care professionals and professional organisations need support of policy at national level.

The ethics of disclosing genetic diagnosis for Alzheimer's disease: do we need a new paradigm?

INTRODUCTION OR BACKGROUND: Genetic testing for rare Mendelian disorders represents the dominant ethical paradigm in clinical and professional practice. Predictive testing for Huntington's disease is the model against which other kinds of genetic testing are evaluated, including testing for Alzheimer's disease. SOURCES OF DATA: This paper retraces the historical development of ethical reasoning in relation to predictive genetic testing and reviews a range of ethical, sociological and psychological literature from the 1970s to the present. AREAS OF AGREEMENT: In the past, ethical reasoning has embodied a distinct style whereby normative principles are developed from a dominant disease exemplar. AREAS OF CONTROVERSY: This reductionist approach to formulating ethical frameworks breaks down in the case of disease susceptibility. GROWING POINTS: Recent developments in the genetics of Alzheimer's disease present a significant case for reconsidering the ethics of disclosing risk for common complex diseases. Disclosing the results of susceptibility testing for Alzheimer's disease has different social, psychological and behavioural consequences. Furthermore, what genetic susceptibility means to individuals and their families is diffuse and often mitigated by other factors and concerns. AREAS TIMELY FOR DEVELOPING RESEARCH: The ethics of disclosing a genetic diagnosis of susceptibility is contingent on whether professionals accept that probabilistic risk information is in fact 'diagnostic' and it will rely substantially on empirical evidence of how people actually perceive, recall and communicate complex risk information.

[Prenatal diagnostics and information to parents]. / Diagnósticos prenatales: información a los padres.

New screening and prenatal diagnostic techniques, require the Medicine professionals have a clear purpose for its realization, since the intention determined the act is determined in accordance with the values of the Medicine or becoming an event eugenics act by means of "therapeutic abortion". The Family Physician information about these techniques to pregnant women must be based on the status of science, facilitating the risk of loss fetal and false data positive informing of therapeutic possibilities and facilitating respect for the pregnant woman's decision of non-fulfillment of the screening. The information update according to the state of science, should be provided in writing and the informed consent of the patient should be obtained by all professionals involved in testing, with respect shows for the autonomy of the patient.

Educational and social-ethical issues in the pursuit of molecular medicine.

Molecular medicine is transforming everyday clinical practice from an empirical art to a rational ortho-molecular science. The prevailing concept in this emerging framework of molecular medicine is a personalized approach to disease prevention, diagnosis, prognosis, and treatment. In this mini-review, we discuss the educational and social-ethical issues raised by the advances of biomedical research as related to medical practice; outline the implications of molecular medicine for patients, physicians, and researchers; and underline the responsibilities of academia and the pharmaceutical industry to translate the scientific knowledge to a meaningful improvement of the quality of life across all members of society.

[Neonatal screening: trends, debates and consensus]. / Dépister les nouveau-nés: évolutions, débats et consensus.

This study focuses on the social and political implications of the substantial expansion of genetic tests and neonatal screening. The introduction of neonatal screening for cystic fibrosis is one of the significant developments that have fuelled debate on their appropriateness. It has raised a series of questions on the pros and cons, the role of evidence in biomedicine, and the articulation between the therapeutic approach and foetal selection. In this respect France provides an ideal research field as it was one of the first countries to generalize this screening, launched in January 2002. Several questions arise: What were the terms of the debate in France and their underlying logics? How was consensus reached? More generally, what does this screening tell us about policies on life forms today?

Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: The U.S. Preventive Services Task Force (USPSTF) has not previously considered screening for hereditary hemochromatosis for a recommendation as a clinical preventive service for primary care clinicians. PURPOSE: To conduct a focused systematic review of hereditary hemochromatosis screening relating to 2 USPSTF criteria, the burden of suffering and the potential effectiveness of a preventive intervention, to determine whether evidence is sufficient for a USPSTF recommendation. DATA SOURCES: MEDLINE, CINAHL, and Cochrane Library databases from 1966 through February 2005. The authors supplemented literature searches with source materials from experts in the field and the bibliographies of key reviews and included studies. STUDY SELECTION: Studies were retrieved to answer 3 key questions: 1) What is the risk for developing clinical hemochromatosis among those with a homozygous C282Y genotype? 2) Does earlier therapeutic phlebotomy of individuals with primary iron overload due to hereditary hemochromatosis reduce morbidity and mortality compared with treatment after diagnosis in routine clinical care? 3) Are there groups at increased risk for developing hereditary hemochromatosis that can be readily identified before genetic screening? The authors critically appraised studies using quality criteria specific to their design. DATA EXTRACTION: The authors abstracted all studies into evidence tables using condition definitions and diagnostic criteria. DATA SYNTHESIS: Data were insufficient to define a very precise estimate of penetrance. Available data suggest that up to 38% to 50% of C282Y homozygotes may develop iron overload, with up to 10% to 33% eventually developing hemochromatosis-associated morbidity. Prevalence of C282Y homozygosity is higher in family members of probands and other high-risk patient groups defined by signs, symptoms, and phenotypic screening. LIMITATIONS: This review considered genetic screening for HFE-related hereditary hemochromatosis in C282Y homozygotes only. Available research is limited, is based solely on observational designs, and is plagued by poor or inconsistent reporting. CONCLUSIONS: Research addressing genetic screening for hereditary hemochromatosis remains insufficient to confidently project the impact of, or estimate the benefit from, widespread or high-risk genetic screening for hereditary hemochromatosis.

Ethical issues and policy analysis for genetic testing: Huntington's disease as a paradigm for diseases with a late onset.

This paper discusses the main ethical issues that arise when testing for genetic diseases with a late adult onset, such as Huntington's disease, take place. It is imperative to study genetic testing for HD and similar diseases because of the potential to influence future medical advances and the growing number of individuals who are considered pre-symptomatic. The main ethical issues are consent and privacy, prenatal testing and its implications, in addition to insurance discrimination. These issues are viewed from the perspective of genetic counselors, patients, the families of patients, and insurance companies. Policies put forth by the United States National Society of Genetic Counselors ("NSGC"), the Task Force on Genetic Testing, and the President's Council for Bioethics are also analyzed. Finally, new recommendations are proposed in order to ameliorate the ethical dilemmas encountered in genetic testing. These recommendations are largely based on existing policies and therefore involve amending current policies rather than revamping them.

Nurses' views of longitudinal genetic screening of and research on children.

There is a lack of empirical data exploring ethical issues of genetic screening and longitudinal research involving children. Therefore, this pilot interview study explored the perceptions of nurses and midwives in relation to their involvement in an ongoing genetic preventive screening process involving children - the All Babies in South-east Sweden (ABIS) study (n=17,005). Data were collected through semistructured interviews with 10 nurses involved in all information and sampling procedures. While providing the preliminary nature of this study, it supports the idea of the importance of further research, both from a nursing professional perspective and from other parties involved in clinical research. The findings made in this study suggest that for such studies it is vital that nurses and midwives are fully informed about aims, methods, and potential intervention/prevention since in many cases they have a central role in several areas of screening and clinical longitudinal research involving children, e.g. information to potential research participants, obtaining informed consent, and data collection. With a thorough understanding of the research, including both basic aims and methods as well as potential future prevention aims, the nursing staff involved will be better placed to help participants make an informed choice and to provide additional information to the participants. Further research may be needed that aims to develop effective methods in preparing data collectors. It is also suggested that the design of the information process, and especially in longitudinal research involving young children, is of utmost importance before such studies are commenced.

Harnessing the potential of cancer genetics in healthcare.

The advancement of knowledge in genetics will have a profound effect on prediction, prevention, and treatment of cancer. It has the potential to offer more personalised healthcare that accords with an individual's genetic profile. However, the complex medical, ethical, legal, and psychosocial issues brought by our ability to test healthy individuals for cancer predisposition and the fast pace of advances in genetics pose great challenges to the medical community. Individuals and families are unlikely to benefit from an effective and ethical application of new genetic knowledge unless high quality cancer-genetics services are developed and integrated into mainstream healthcare, more research is undertaken into the prevention, causes, and treatment of cancer, and further efforts are made to improve public understanding and acceptance of cancer genetics.

FACE facts: why human genetics will always provoke bioethics.

Some people dispute the relative importance of issues in genetics and biotechnology for the future of bioethics, either because they think the problems are time-limited or because they give priority to issue of human rights and social justice in health care. In fact, the special historical standing of genetic issue s in bioethics reflects four overlapping sources of moral sensitivity which ar inherent in the stories that genetic science tells and raise paradigmatic justice concerns: the implications of new genetic knowledge for people's understanding of their familial roles, ancestral origins, community memberships, and ethnic affiliations. Beneath worries over "genetic privacy," "the therapeutic gap," and the "post-human," this constellation of basic wellspring which both insures and justifies a central place for genetics on the agenda of bioethics.