M.C. Cornel

Neonatal Screening for Treatable and Untreatable Disorders: Prospective Parents’ Opinions

OBJECTIVE: In the Netherlands, in 2007, the national newborn screening program was expanded from 3 to 17 disorders that met the World Health Organizations Wilson and Jungner screening criteria, especially regarding treatability. The decision of whether to add diseases to the program is generally based on experts advice, whereas the opinion of those whom it concerns—prospective parents—remains unknown. In this study, we investigated the opinion of prospective parents concerning newborn screening for disorders that are incurable yet treatable to some extent or even untreatable. METHODS: A structured questionnaire that consisted of 3 parts in which similar questions were posed about treatable, less treatable, and untreatable childhood-onset disorders was posted on the Web site of a national pregnancy fair. RESULTS: A total of 1631 prospective parents filled out the questionnaire, 259 of whom were excluded. In contrast to current policy, respondents showed a positive attitude toward inclusion of less treatable (88%) or untreatable childhood-onset disorders (73%) within the national newborn screening program. Respondents who already had children at the time of completing the questionnaire were even more in favor of screening for especially untreatable disorders. The most important reason mentioned was to prevent a long diagnostic quest. Obtaining information to enable reproductive choices in future pregnancies was hardly mentioned. CONCLUSIONS: Prospective parents in the Dutch population seem interested in newborn screening for untreatable childhood-onset disorders; therefore, we argue that additional debate of pros and cons is needed among policy makers, health care professionals, and consumers.

'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.

Responsible innovation in human germline gene editing. Background document to the recommendations of ESHG and ESHRE

Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, preclinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g., gene editing goes against nature) do not seem convincing while consequentialist objections (e.g., safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.

Policy Making in Newborn Screening Needs a Structured and Transparent Approach

Purpose Newborn bloodspot screening (NBS) programs have expanded significantly in the past years and are expected to expand further with the emergence of genetic technologies. Historically, NBS expansion has often occurred following ad hoc consideration of conditions, instead of a structured and transparent approach. In this review, we explore issues pertinent to NBS policy making, through the lens of the policy cycle: (a) agenda setting, (b) policy advice, (c) policy decision, (d) implementation, and (e) evaluation. Methods A literature search was conducted to gather information on the elements specific to NBS and its policy making process. Results The review highlighted two approaches to nominate a condition: a structured approach through horizon scanning; and an ad hoc process. For assessment of a condition, there was unanimous support for a robust process based on criteria. While the need to assess harms and benefits was a repeated theme in the articles, there is no agreed-upon threshold for benefit in decision-making. Furthermore, the literature was consistent in its recommendation for an overarching, independent, multidisciplinary group providing recommendations to government. An implementation plan focusing on the different levels on which NBS operates and the information needed on each level is essential for successful implementation. Continuously monitoring, and improving a program is vital, particularly following the implementation of screening for a new condition. An advisory committee could advise on implementation, development, review, modification, and cessation of (parts of) NBS. Conclusion The results highlight that there are a wave of issues facing NBS programs that policy makers must take into account when developing policy processes. What conditions to screen, and the technologies used in NBS, are both up for debate.

Genetische screening: het perspectief van de potentiële gebruiker

De snelle ontwikkelingen in het genomicsonderzoek leiden tot hoge verwachtingen ten aanzien van nieuwe toepassingen in de gezondheidszorg. Om voor- en nadelen van genetische screening te kunnen afwegen wordt gebruik gemaakt van criteria die aanvankelijk zijn opgesteld door Wilson en Jungner voor de Wereldgezondheidsorganisatie en door de Gezondheidsraad verder zijn uitgewerkt. Dit verkennende kwalitatieve onderzoek richt zich op de vraag hoe vanuit het gebruikersperspectief wordt aangekeken tegen genetische screening. Welke aspecten betrekken potentiële gebruikers in hun overwegingen bij de beoordeling van een genetisch screeningsaanbod? In hoeverre komen de overwegingen die gebruikers maken ten aanzien van een potentieel screeningsaanbod overeen met de aandachtspunten die beschreven staan in de genetische screeningscriteria van de Gezondheidsraad en het Nederlandse genetische screeningsbeleid? Acht focusgroepen zijn samengesteld met mensen in verschillende levensfasen die wel en niet bekend zijn met een erfelijke aandoening. De focusgroepbijeenkomsten hebben inzichtelijk gemaakt dat elke afweging ten aanzien van een genetisch screeningsaanbod zeer persoonlijk is. Dit geldt ook voor screening op onbehandelbare aandoeningen. De overheid voert op basis van genoemde criteria ten aanzien van bevolkingsonderzoek in het algemeen en genetische screening op onbehandelbare aandoeningen in het bijzonder een terughoudend beleid. Voor persoonlijke keuzes door de burger is weinig ruimte.Genetic screening: the user’s perspective. An exploratory qualitative studySome expect that genomics research will lead to an increase of the possibilities for genetic screening. Screening criteria are used to assess advantages and disadvantages of (genetic) screening programs. These criteria were originally formulated by Wilson and Junger for the World Health Organization and have been adapted by the Health Council of the Netherlands. This exploratory, qualitative study aims to investigate how potential users appreciate genetic screening. What aspects are relevant for potential users when considering an offer for genetic screening? To which extent do the considerations of potential users meet the points of attention of the Dutch genetic screening criteria and the current Dutch screening policy? Eight focus groups were composed of people in different phases of life who either did or did not have a family history of genetic disease. The focus group meetings showed that weighing pros and cons of a genetic screening offer is a very personal matter. This also holds true for untreatable conditions. Current governmental policy is restrictive regarding genetic screening, especially when untreatable disorders are concerned. This leaves not much leeway for personal choices.De snelle ontwikkelingen in het genomicsonderzoek leiden tot hoge verwachtingen ten aanzien van nieuwe toepassingen in de gezondheidszorg. Om voor- en nadelen van genetische screening te kunnen afwegen wordt gebruik gemaakt van criteria die aanvankelijk zijn opgesteld door Wilson en Jungner voor de Wereldgezondheidsorganisatie en door de Gezondheidsraad verder zijn uitgewerkt. Dit verkennende kwalitatieve onderzoek richt zich op de vraag hoe vanuit het gebruikersperspectief wordt aangekeken tegen genetische screening. Welke aspecten betrekken potentiele gebruikers in hun overwegingen bij de beoordeling van een genetisch screeningsaanbod? In hoeverre komen de overwegingen die gebruikers maken ten aanzien van een potentieel screeningsaanbod overeen met de aandachtspunten die beschreven staan in de genetische screeningscriteria van de Gezondheidsraad en het Nederlandse genetische screeningsbeleid? Acht focusgroepen zijn samengesteld met mensen in verschillende levensfasen die wel en niet bekend zijn met een erfelijke aandoening. De focusgroepbijeenkomsten hebben inzichtelijk gemaakt dat elke afweging ten aanzien van een genetisch screeningsaanbod zeer persoonlijk is. Dit geldt ook voor screening op onbehandelbare aandoeningen. De overheid voert op basis van genoemde criteria ten aanzien van bevolkingsonderzoek in het algemeen en genetische screening op onbehandelbare aandoeningen in het bijzonder een terughoudend beleid. Voor persoonlijke keuzes door de burger is weinig ruimte.

The ethics of clinical applications of germline genome modification: a systematic review of reasons

STUDY QUESTIONnWhat are the reasons for or against the future clinical application of germline genome modification (GGM)?nnnSUMMARY ANSWERnA total of 169 reasons were identified, including 90 reasons for and 79 reasons against future clinical application of GGM.nnnWHAT IS KNOWN ALREADYnGGM is still unsafe and insufficiently effective for clinical purposes. However, the progress made using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated system (Cas) has led scientists to expect to overcome the technical hurdles in the foreseeable future. This has invited a debate on the socio-ethical and legal implications and acceptability of clinical applications of GGM. However, an overview of the reasons presented in this debate is missing.nnnSTUDY DESIGN, SIZE, DURATIONnMEDLINE was systematically searched for articles published between January 2011 and June 2016. Articles covering reasons for or against clinical application of intentional modification of the nuclear DNA of the germline were included.nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnTwo researchers independently extracted the reported reasons from the articles and grouped them into categories through content analysis.nnnMAIN RESULTS AND THE ROLE OF CHANCEnThe systematic search yielded 1179 articles and 180 articles were included. Most papers were written by professionals in ethics, (science) journalism and biomedical sciences. Overall, 169 reasons were identified, including 90 reasons for, and 79 reasons against future clinical application of GGM. None of the included articles mentioned more than 60/169 reasons. The reasons could be categorized into: (i) quality of life of affected individuals; (ii) safety; (iii) effectiveness; (iv) existence of a clinical need or alternative; (v) costs; (vi) homo sapiens as a species (i.e. relating to effects on our species); (vii) social justice; (viii) potential for misuse; (ix) special interests exercising influence; (x) parental rights and duties; (xi) comparability to acceptable processes; (xii) rights of the unborn child; and (xiii) human life and dignity. Considerations relating to the implementation processes and regulation were reported.nnnLIMITATIONS, REASONS FOR CAUTIONnWe cannot ensure completeness as reasons may have been omitted in the reviewed literature and our search was limited to MEDLINE and a 5-year time period.nnnWIDER IMPLICATIONS OF THE FINDINGSnBesides needing (pre)clinical studies on safety and effectiveness, authors call for a sound pre-implementation process. This overview of reasons may assist a thorough evaluation of the responsible introduction of GGM.nnnSTUDY FUNDING/COMPETING INTEREST(S)nUniversity of Amsterdam, Alliance Grant of the Amsterdam Reproduction and Development Research Institute (I.D.), and Clinical Center, Department of Bioethics, National Institutes of Health Intramural Research Program (S.H.). There are no competing interests.

The Gen-Equip Project: evaluation and impact of genetics e-learning resources for primary care in six European languages

PurposeGenetic advances mean patients at risk of genetic conditions can be helped through testing, clinical screening, and preventive treatment, but they must first be identified to benefit. Ensuring quality of genetic care for patients requires genetic expertise in all health services, including primary care. To address an educational shortfall, a series of e-learning resources was developed in six languages to equip primary care professionals with genetic skills relevant for practice. The purpose of the study was to evaluate these resources using Kirkpatrick’s framework for educational outcomes.MethodsMixed methods (qualitative and quantitative) were used over four phases of the study.ResultsA high level of satisfaction with the resources was reported. Knowledge and skills improved significantly after using the education material. Participants reported changes in confidence and practice behavior, including family history taking, seeking advice from specialists and referring patients. The resources helped users to learn how to explain genetics. Many visited the resources repeatedly and some used them to educate colleagues or students.ConclusionGen-Equip modules are effective in improving genetic knowledge, skills, and attitudes for primary care professionals. They provide both continuing professional development and just-in-time learning for a potentially large global audience at a practical level.

Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective

More than 15u2009years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

Raw Data: Research and Health Care Goals Differ

In their Policy Forum “Raw personal data: Providing access” (24 January, p. [373][1]), J. E. Lunshof et al. suggest that more should be done to enable persons who had their genome sequenced, either as research subjects or as patients, to actively access their raw data. They argue that routinely providing them with personal access codes to those data would be a matter of transparency and respect for autonomy. We think Lunshof et al. underestimate the dangers of actively handing out data that we know are not fully reliable and can lead to misinterpretation. In our view, the proposed policy would be at odds with the responsibility of health professionals.nnIn health care, clinical utility should have priority over social utility. An appeal to reciprocity between donors and users of genomic data does not change this argument. Patients are not the same as data donors. If patients become data donors by consenting to have their data stored in research registries, they should be aware that they have entered a different relationship, in which they primarily contribute to the benefit of future patients.nnLunshof et al. ignore the crucial difference between health care and research when they criticize the recent recommendations of the European Society of Human Genetics (ESHG). To avoid the unnecessary generation of incidental findings, these recommendations advise the use of targeted forms of testing if that is sufficient to address the patients problem ([ 1 ][2]). According to Lunshof et al. , this is problematic as it “systematically precludes the possible discovery of complex genetic causation.” We disagree: Discovery is the aim of research, not of health care. Conflating these aims risks turning patients into research subjects without their consent.nn1. [↵][3] 1. C. G. van El 2. et aln ., Eur. J. Hum. Genet. 21, 580 (2013).n [OpenUrl][4][PubMed][5]nn2. The authors are writing on behalf of the ESHG Public and Professional Policy Committee.nn [1]: /lookup/doi/10.1126/science.1249382n [2]: #ref-1n [3]: #xref-ref-1-1 View reference 1 in textn [4]: {openurl}?query=rft.jtitle%253DEur.%2BJ.%2BHum.%2BGenet.%26rft.volume%253D21%26rft.spage%253D580%26rft_id%253Dinfo%253Apmid%252F23676617%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actxn [5]: /lookup/external-ref?access_num=23676617&link_type=MED&atom=%2Fsci%2F343%2F6174%2F968.2.atom