Newborn screening for pompe disease? A qualitative study exploring professional views

Background: Developments in enzyme replacement therapy have kindled discussions on adding Pompe disease, characterized by progressive muscle weakness and wasting, to neonatal screening. Pompe disease does not fit traditional screening criteria as it is a broad-spectrum phenotype disorder that may occur in lethal form in early infancy or manifest in less severe forms from infancy to late adulthood. Current screening tests cannot differentiate between these forms. Normally, expanding screening is discussed among experts in advisory bodies. While advisory reports usually mention the procedures and outcome of deliberations, little is known of the importance attached to different arguments and the actual weighing processes involved. In this research we aim to explore the views of a wide range of relevant professionals to gain more insight into the process of weighing pros and cons of neonatal screening for Pompe disease, as an example of the dilemmas involved in screening for broad-spectrum phenotype disorders.Methods: We conducted 24 semi-structured interviews with medical, lab, insurance and screening professionals, and executive staff of patient organisations. They were asked about their first reaction to neonatal screening for Pompe disease, after which benefits and harms and requirements for screening were explored in more detail.Results: Advantages included health gain by timely intervention, avoiding a diagnostic quest, having a reproductive choice and gaining more knowledge about the natural course and treatment. Being prepared was mentioned as an advantage for the later manifesting cases. Disadvantages included treatment costs and uncertainties about its effect, the timing of treatment in later manifesting cases, the psychological burden for the patient-in-waiting and the family. Also the downsides of having prior knowledge as well as having to consider a reproductive option were mentioned as disadvantages.Conclusion: When weighing pros and cons, interviewees attach different importance to different arguments, based on personal and professional views. Professionals expect benefits from neonatal screening for Pompe disease, especially for early-onset cases. Some interviewees valued screening in later manifesting cases as well, while stressing the need for adequate support of pre-symptomatic patients and their families. Others considered the psychological burden and uncertainties regarding treatment as reasons not to screen

Challenges and opportunities for ELSI early career researchers

Background: Over the past 25 years, there has been growing recognition of the importance of studying the Ethical, Legal and Social Implications (ELSI) of genetic and genomic research. A large investment into ELSI research from the National Institutes of Health (NIH) Human Genomic Project budget in 1990 stimulated the growth of this emerging field; ELSI research has continued to develop and is starting to emerge as a field in its own right. The evolving subject matter of ELSI research continues to raise new research questions as well as prompt re-evaluation of earlier work and a growing number of scholars working in this area now identify themselves as ELSI scholars rather than with a particular discipline. Main text: Due to the international and interdisciplinary nature of ELSI research, scholars can often find themselves isolated from disciplinary or regionally situated support structures. We conducted a workshop with Early Career Researchers (ECRs) in Oxford, UK, and this paper discusses some of the particular challenges that were highlighted. While ELSI ECRs may face many of the universal challenges faced by ECRs, we argue that a number of challenges are either unique or exacerbated in the case of ELSI ECRs and discuss some of the reasons as to why this may be the case. We identify some of the most pressing issues for ELSI ECRs as: interdisciplinary angst and expertise, isolation from traditional support structures, limited resources and funding opportunities, and uncertainty regarding how research contributions will be measured. We discuss the potential opportunity to use web 2.0 technologies to transform academic support structures and address some of the challenges faced by ELSI ECRs, by helping to facilitate mentoring and support, access to resources and new accreditation metrics. Conclusion: As our field develops it is crucial for the ELSI community to continue looking forward to identify how emerging digital solutions can be used to facilitate the international and interdisciplinary research we perform, and to offer support for those embarking on, progressing through, and transitioning into an ELSI research career.COST Action IS1303Wellcome Trust/096599/2/11/

Roles and Responsibilities of Stakeholders in Informing Healthy Individuals on Their Genome: A Sociotechnical Analysis

For some common disorders (cancer, cardiovascular disease (CVD)) monogenic subtypes exist where variants in one gene increase the risk substantially, and interventions are available to prevent mortality and morbidity. After identifying an affected index case, first-degree relatives often are still healthy but have a 50% risk of carrying the gene variant. In the last decade in theory possibilities for DNA testing to early identify high-risk relatives have increased, but few systematic cascade screening programmes have been developed. In this chapter, we will provide theoretical background for sociotechnical analysis, and elaborate the potential of increased efforts to identify people who carry an inherited predisposition to develop cancer (esp. Lynch Syndrome (LS)) or CVDs (esp. Familial Hypercholesterolaemia (FH)). The theoretical framework serves to clarify roles and responsibilities in efforts to improve aspects of healthcare. In a changing culture (especially moving from cure to prevention) structural changes may be needed (e.g. allowing non-genetic healthcare providers to order genetic tests) and practice needs to be differently organised. Silo structures tend to restrict the focus of medical specialists to the individual patient. To systematically inform relatives, the experience of clinical genetics could be used in other sectors of healthcare. The responsibility to protect the health of the public could result in a public health screening programme for healthy relatives. Responsible implementation of such a cascade screening programme does not occur without a deliberate effort

Neonatal and carrier screening for rare diseases: how innovation challenges screening criteria worldwide

Screening for rare diseases first began more than 50 years ago with neonatal bloodspot screening (NBS) for phenylketonuria, and carrier screening for Tay-Sachs disease, sickle cell anaemia and β-thalassaemia. NBS’s primary aim is health gain for children, while carrier screening enables autonomous reproductive choice. While screening can be beneficial, it also has the potential to cause harm and thus decisions are needed on whether a specific screening is worthwhile. These decisions are usually based on screening principles and criteria. Technological developments, both treatment driven and test driven, have led to expansions in neonatal screening and carrier screening. This article demonstrates how the dynamics and expansions in NBS and carrier screening have challenged four well-known screening criteria (treatment, test, target population and programme evaluation), and the decision-making based on them. We show that shifting perspectives on screening criteria for NBS as well as carrier screening lead to converging debates in these separate fields. For example, the child is traditionally considered to be the beneficiary in NBS, but the family and society can also benefit. Vice versa, carrier screening may be driven by disease prevention, rather than reproductive autonomy, raising cross-disciplinary questions regarding potential beneficiaries and which diseases to include. In addition, the stakeholders from these separate fields vary: Globally NBS is often governed as a public health programme while carrier screening is usually available via medical professionals. The article concludes with a call for an exchange of vision and knowledge among all stakeholders of both fields to attune the dynamics of screening

Moving somatic gene editing to the clinic: routes to market access and reimbursement in Europe

Somatic gene editing (SGE) holds great promise for making genetic therapy possible for many monogenic conditions very soon. Is our current system of European market authorization and reimbursement ready for the expected tsunami of gene therapies? At a recent workshop of the Netherlands ZonMw consortium on ethical, legal, and social implications of personalized medicine, we discussed the current possibilities for bringing new gene therapies to the clinic. In Europe, it is not yet clear whether the route via the European medicines agency as an advanced therapy medicinal product is the most appropriate for evaluation of highly personalized SGE applications, although this may optimally guarantee safety and effectiveness. Compassionate use may ensure faster access than the centralized procedure but does not stimulate the commercial development of products. Prescription to named patients may only provide adequate access for single patients. Temporary authorization of use may allow access to medication half a year before formal market authorization has been granted, but may also have large budget impacts. Magistral compounding under a hospital exemption may be an attractive solution for rare, tailor-made applications at an acceptable price. To approve local experimental use of a therapy on a case-by-case basis may be fast, but does not guarantee optimal safety, effectiveness, and broad implementation. We argue that alternative routes should be considered for products developed for a market of large groups of patients versus unique personalized treatments. A balance between scientific evidence for safety and effectiveness, affordability, and fast access may demand a range of alternative solutions

Pursuing Public Health Benefit Within National Genomic Initiatives: Learning From Different Policies.

Introduction: Population-based genomic research is expected to deliver substantial public health benefits. National genomics initiatives are widespread, with large-scale collection and research of human genomic data. To date, little is known about the actual public health benefit that is yielded from such initiatives. In this study, we explore how public health benefit is being pursued in a selection of national genomics initiatives. Methods: A mixed-method study was carried out, consisting of a literature-based comparison of 11 purposively sampled national genomics initiatives (Belgium, Denmark, Estonia, Finland, Germany, Iceland, Qatar, Saudi Arabia, Taiwan, United Kingdom (UK), and United States (USA)), and five semi-structured interviews with experts (Denmark, Estonia, Finland, UK, USA). It was analyzed to what extent and how public health benefit was pursued and then operationalized in each phase of an adapted public health policy cycle: agenda setting, governance, (research) strategy towards health benefit, implementation, evaluation. Results: Public health benefit within national genomics initiatives was pursued in all initiatives and also operationalized in all phases of the public health policy cycle. The inclusion of public health benefit in genomics initiatives seemed dependent on the outcomes of agenda setting, such as the aims and values, as well as design of governance, for example involved actors and funding. Some initiatives focus on a research-based strategy to contribute to public health, while others focus on research translation into healthcare, or a combination of both. Evaluation of public health benefits could be performed qualitatively, such as assessing improved public trust, and/or quantitatively, e.g. research output or number of new diagnoses. However, the created health benefit for the general public, both short- and long-term, appears to be difficult to determine. Conclusion: Genomics initiatives hold the potential to deliver health promises of population-based genomics. Yet, universal tools to measure public health benefit and clarity in roles and responsibilities of collaborating stakeholders are lacking. Advancements in both aspects will help to facilitate and achieve the expected impact of genomics initiatives and enable effective research translation, implementation, and ultimately improved public health