Eline M. Bunnik

Personal utility in genomic testing: is there such a thing?

In ethical and regulatory discussions on new applications of genomic testing technologies, the notion of ‘personal utility’ has been mentioned repeatedly. It has been used to justify direct access to commercially offered genomic testing or feedback of individual research results to research or biobank participants. Sometimes research participants or consumers claim a right to genomic information with an appeal to personal utility. As of yet, no systematic account of the umbrella notion of personal utility has been given. This paper offers a definition of personal utility that places it in the middle of the spectrum between clinical utility and personal perceptions of utility, and that acknowledges its normative charge. The paper discusses two perspectives on personal utility, the healthcare perspective and the consumer perspective, and argues that these are too narrow and too wide, respectively. Instead, it proposes a normative definition of personal utility that postulates information and potential use as necessary conditions of utility. This definition entails that perceived utility does not equal personal utility, and that expert judgment may be necessary to help determine whether a genomic test can have personal utility for someone. Two examples of genomic tests are presented to illustrate the discrepancies between perceived utility and our proposed definition of personal utility. The paper concludes that while there is room for the notion of personal utility in the ethical evaluation and regulation of genomic tests, the justificatory role of personal utility is not unlimited. For in the absence of clinical validity and reasonable potential use of information, there is no personal utility.

Informed Consent in Direct‐To‐Consumer Personal Genome Testing: The Outline of a Model between Specific and Generic Consent

Broad genome-wide testing is increasingly finding its way to the public through the online direct-to-consumer marketing of so-called personal genome tests. Personal genome tests estimate genetic susceptibilities to multiple diseases and other phenotypic traits simultaneously. Providers commonly make use of Terms of Service agreements rather than informed consent procedures. However, to protect consumers from the potential physical, psychological and social harms associated with personal genome testing and to promote autonomous decision-making with regard to the testing offer, we argue that current practices of information provision are insufficient and that there is a place--and a need--for informed consent in personal genome testing, also when it is offered commercially. The increasing quantity, complexity and diversity of most testing offers, however, pose challenges for information provision and informed consent. Both specific and generic models for informed consent fail to meet its moral aims when applied to personal genome testing. Consumers should be enabled to know the limitations, risks and implications of personal genome testing and should be given control over the genetic information they do or do not wish to obtain. We present the outline of a new model for informed consent which can meet both the norm of providing sufficient information and the norm of providing understandable information. The model can be used for personal genome testing, but will also be applicable to other, future forms of broad genetic testing or screening in commercial and clinical settings.

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review

BackgroundCurrent Alzheimer’s disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants.MethodsWe performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group.ResultsFourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning.ConclusionIn cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed.Trial registrationPROSPERO international prospective register for systematic reviews CRD42016035388. Registered 19 February 2016.

Naming and framing in genomic testing.

Whats in a name? Terminology has the power to shape the ethical and regulatory debate surrounding commercially offered genomic testing. This article discusses the normative effects of naming and framing, and proposes that the medical frame, with its focus on the reduction of harm, should be used in the evaluation and regulation of predictive genomic testing.

Perspectives on Communicating Biomarker-Based Assessments of Alzheimer's Disease to Cognitively Healthy Individuals.

In clinical trials which target pathophysiological mechanisms associated with Alzheimer’s disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer’s dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants’ experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer’s disease biomarkers.

The changing landscape of expanded access to investigational drugs for patients with unmet medical needs: ethical implications

When patients are told that standard medical treatment options have been exhausted, their treating physicians may start looking for promising new drugs that are not yet approved, and still under investigation. Some patients can be included in clinical trials, but others cannot. It is not widely known that these patients might still be eligible for trying investigational drugs, in a therapeutic context. Worldwide, public and private parties are seeking to change this by informing patients and physicians about opportunities for expanded access and/or by facilitating its processes. When expanded access becomes available to larger groups of patients, ethical issues gain prominence, including informed consent, funding issues, disparities in access, and potential adverse effects on clinical drug development. Physicians, patients and policy-makers should not shift the responsibility to address these issues to pharmaceutical companies, but work together to resolve them.

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.

Do genomic tests enhance autonomy

It is not a bad idea to assess whether direct-to-consumer (DTC) genomic tests are a threat to or instead an enhancement of autonomy, as is done in the article ‘Direct to consumer genomics on the scales of autonomy’ by Effy Vayena.1 Autonomy has played a starring role in ethical discussions surrounding DTC genomic testing, but has taken many different shapes. Vayena deploys Joseph Raz’ conception of autonomy, which entails that genomic tests enhance autonomy if they present the consumer with an adequate—that is, varied and morally worthwhile—range of options to choose from, which should promote the consumers interests. She states that genomic tests generate ‘plural utilities’ that are taken to expand the range of valuable options and therewith to satisfy Raz’ thick conception of autonomy. Thus, Vayena makes an autonomy-based case in favour of legal permissibility of commercially offered genomic tests. The analysis however overlooks three crucial considerations. First, there is no such thing as ‘genomic testing’. Plenitudes of genomic tests have been put to market, with different underlying techniques and test characteristics, different diseases and other phenotypical traits included in the testing offer, and …

On the personal utility of Alzheimer’s disease-related biomarker testing in the research context

Many healthy volunteers choose to take part in Alzheimer’s disease (AD) prevention studies because they want to know whether they will develop dementia—and what they can do to reduce their risk—and are therefore interested in learning the results of AD biomarker tests. Proponents of AD biomarker disclosure often refer to the personal utility of AD biomarkers, claiming that research participants will be able to use AD biomarker information for personal purposes, such as planning ahead or making important life decisions. In this paper, the claim that AD biomarkers have personal utility for asymptomatic individuals is critically assessed. It demonstrates that in the absence of clinical validity, AD biomarkers cannot have personal utility and do not serve research participants’ autonomy. Over the next few years, many research groups will be confronted with participants’ preferences to learn the results of AD biomarker tests. When researchers choose to make results available upon explicit request, they should ensure adequate information provision and education, notably on the uncertain clinical significance of AD biomarker information. Routine disclosure of AD biomarkers to cognitively unimpaired individuals in research settings cannot be justified with an appeal to the personal utility of AD biomarker information.

Ethics of routine: a critical analysis of the concept of ‘routinisation’ in prenatal screening

In the debate surrounding the introduction of non-invasive prenatal testing (NIPT) 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: (1) informed choice, (2) freedom to choose and (3) 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.