Up Close and Personal : Ethical issues in genomic testing

__Abstract__ Achilles was foretold to die young. When he was still a baby, his mother Thetis took him to the river Styx, which separated the world of the living from the realm of Hades. The waters of the Styx were known to bring invulnerability to those who were touched by them. Thetis bathed the infant in the magical Styx. After that, Achilles lived, grew and flourished. As he came of age, Achilles became a fearless warrior and a leader in the Trojan War, during which he acquired a reputation of unassailability. Until, in the midst of battle, a poisonous arrow pierced through Achilles’ heel, and killed him... Thetis had held her baby by the heel when she submerged him in the Styx. The waters had left only Achilles’ heel vulnerable

Ethical Issues in Research and Development of Epigenome-wide Technologies

To date, few scholarly discussions on ethical implications of epigenetics and epigenomics technologies have focused on the current phase of research and development, in which researchers are confronted with real and practical ethical dilemmas. In this article, a responsible research and innovation approach, using interviews and an expert meeting, is applied to a case of epigenomic test development for cervical cancer screening. This article provides an overview of ethical issues presently facing epigenomics researchers and test developers, and discusses 3 sets of issues in depth: (1) informed consent; (2) communication with donors and/or research participants, and (3) privacy and publication of data and research results. Although these issues are familiar to research ethics, some aspects are new and most require reinterpretation in the context of epigenomics technologies

The Role of Physicians in Expanded Access to Investigational Drugs: A Mixed-Methods Study of Physicians’ Views and Experiences in The Netherlands

Treating physicians have key roles to play in expanded access to investigational drugs, by identifying investigational treatment options, assessing the balance of risks and potential benefits, informing their patients, and applying to the regulatory authorities. This study is the first to explore physicians’ experiences and moral views, with the aim of understanding the conditions under which doctors decide to pursue expanded access for their patients and the obstacles and facilitators they encounter in the Netherlands. In this mixed-methods study, semi-structured interviews (n = 14) and a questionnaire (n = 90) were conducted with medical specialists across the country and analysed thematically. Typically, our respondents pursue expanded access in “back against the wall” situations and broadly support its classic requirements. They indicate practical hurdles related to reimbursement, the amount of time and effort required for the application, and unfamiliarity with the regulatory process. Some physicians are morally opposed to expanded access, with an appeal to safety risks, lack of evidence, and “false hope.” Some of these moral concerns and practical obstacles may be essential targets for change, if expanded access to unapproved drugs is to become available for wider groups of patients for whom standard treatment options are not—or no longer—available, on a more consistent and equal basis

What do patients with unmet medical needs want? A qualitative study of patients' views and experiences with expanded access to unapproved, investigational treatments in the Netherlands

Background: Patients with unmet medical needs sometimes resort to non-standard treatment options, including the use of unapproved, investigational drugs in the context of clinical trials, compassionate use or named-patient programs. The views and experiences of patients with unmet medical needs regarding unapproved, investigational drugs have not yet been examined empirically. Methods: In this qualitative study, exploratory interviews and focus groups were held with patients with chronic or life-threatening diseases (n = 39), about topics related to non-standard treatment options, such as the search for non-standard treatment options, patients' views of the moral obligations of doctors, and the conditions under which they would or would not wish to use non-standard treatment options, including expanded access to unapproved, investigational drugs. Results: Respondents had very little knowledge about and/or experience with existing opportunities for expanded access to investigational drugs, although some respondents were actively looking for non-standard treatment options. They had high expectations of their treating physicians, assuming them to be aware of non-standard treatment options, including clinical trials elsewhere and expanded access programs, and assuming that they would inform their patients about such options. Respondents carefully weighed the risks and potential benefits of pursuing expanded access, citing concerns related to the scientific evidence of the safety and efficacy of the drug, side effects, drug-drug interactions, and the maintaining of good quality of life. Respondents stressed the importance of education and assertiveness to obtain access to good-quality health care, and were willing to pay out of pocket for investigational drugs. Patients expressed concerns about equal access to new and/or non-standard treatment options. Conclusion: When the end of a standard treatment trajectory comes into view, patients may prefer that treating physicians discuss non-standard treatment options with them, including opportunities for expanded access to unapproved, investigational drugs. Although our respondents had varying levels of understanding of expanded access programs, they seemed capable of making well-considered choices with regard to non-standard treatment options and had realistic expectations with regard to the safety and efficacy of such options. Dutch patients might be less likely to fall prey to false hope than often presumed

Why NIPT should be publicly funded

Asking pregnant women to (co)pay for non-invasive prenatal testing (NIPT) out of pocket leads to unequal access across socioeconomic strata. To avoid these social justice issues, first-trimester prenatal screening should be publicly funded in countries such as the Netherlands, with universal coverage healthcare systems that offer all other antenatal care

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

BACKGROUND: Current 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. METHODS: We 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. RESULTS: Fourteen 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. CONCLUSION: In 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 REGISTRATION: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016

Should pregnant women be charged for non-invasive prenatal screening? Implications for reproductive autonomy and equal access

The introduction of non-invasive prenatal testing (NIPT) in healthcare systems around the world offers an opportunity to reconsider funding policies for prenatal screening. In some countries with universal access healthcare systems, pregnant women and their partners are asked to (co)pay for NIPT. In this paper, we discuss two important rationales for charging women for NIPT: (1) to

The Impact of Incidental Findings Detected During Brain Imaging on Research Participants of the Rotterdam Study: An Interview Study

This interview study investigates the short- and long-term implications of incidental findings detected through brain imaging on research participants’ lives and their surroundings. For this study, nine participants of the Rotterdam Scan Study with an incidental finding were approached and interviewed. When examining research participants’ narratives on the impact of the disclosure of incidental findings, the authors identified five sets of tensions with regard to motivations for and expectations of research participation, preferences regarding disclosure, short- and long-term impacts and impacts on self and others. The paper shows: (1) that the impact of incidental findings may be greater than participants at first let on; (2) incidental findings can have significant effects on participants’ social environment; and (3) participants may not feel prepared for disclosure even if incidental findings have been discussed during the informed consent process. The authors call for investigators to be aware of research participants’ experiences and these short- and long-term impacts when designing suitable courses of action for the detection and management of incidental findings in research settings

Prevention in the age of personal responsibility: Epigenetic risk-predictive screening for female cancers as a case study

Epigenetic markers could potentially be used for risk assessment in risk-stratified population-based cancer screening programmes. Whereas current screening programmes generally aim to detect existing cancer, epigenetic markers could be used to provide risk estimates for not-yet-existing cancers. Epigenetic risk-predictive tests may thus allow for new opportunities for risk assessment for developing cancer in the future. Since epigenetic changes are presumed to be modifiable, preventive measures, such as lifestyle modification, could be used to reduce the risk of cancer. Moreover, epigenetic markers might be used to monitor the response to risk-reducing interventions. In this article, we address ethical concerns related to personal responsibility raised by epigenetic risk-predictive tests in cancer population screening. Will individuals increasingly be held responsible for their health, that is, will they be held accountable for bad health outcomes? Will they be blamed or subject to moral sanctions? We will illustrate these ethical concerns by means of a Europe-wide research programme that develops an epigenetic risk-predictive test for female cancers. Subsequently, we investigate when we can hold someone responsible for her actions. We argue that the standard conception of personal responsibility does not provide an appropriate framework to address these concerns. A different, prospective account of responsibility meets part of our concerns, that is, concerns about inequality of opportunities, but does not meet all our concerns about personal responsibility. We argue that even if someone is responsible on grounds of a negative and/or prospective account of responsibility, there may be moral and practical reasons to abstain from moral sanctions

Implementing non-invasive prenatal testing (NIPT) in the Netherlands: An interview study exploring opinions about and experiences with societal pressure, reimbursement, and an expanding scope

The noninvasive prenatal test (NIPT) as the first trimester prenatal screening (FTS) for trisomies 21, 18, and 13 is offered to all pregnant women in the Netherlands. NIPT using genome sequencing allows for an expansion of the scope of FTS and the introduction of NIPT gives rise to ethical and societal concerns about deliberated decision-making, pressure to engage in screening, and possible lack of equal access due to the financial contribution (€175) to NIPT. We explored the opinions and experiences of pregnant women, who were offered FTS, about these concerns, and the possibility of a broadened scope. Nineteen pregnant women representing a diversity of backgrounds were interviewed using a semi-structured interview guide. Eight women did not opt for prenatal screening while 11 did (NIPT = 4, combined test = 7). Women experienced a free choice to accept or decline prenatal screening, despite sometimes receiving advice from others. Prior to pretest counseling, some women had already deliberated about what an abnormal test result would mean to them. Others accepted or declined FTS without deliberation. The current Dutch policy of requiring a co-payment was acceptable to some, who believed that it functioned as a threshold to think carefully about FTS. Others were concerned that a financial threshold would lead to unequal access to screening. Finally, pregnant women found it difficult to formulate opinions on the scope of FTS, because of lack of knowledge. Life expectancy, severity, and treatability were considered important criteria for the inclusion of a condition in NIPT