Paediatric biobanking: Dutch experts reflecting on appropriate legal standards for practice

Large sets of data and human specimens, such as blood, tumour tissue and DNA, are deposited in biobanks for research purposes, preferably for long periods of time and with broadly defined research aims. Our research focuses on the retention of data and biological materials obtained from children. However important such paediatric biobanks may be, the privacy interests of the children involved and the related risks may not be ignored. The privacy issues arising from paediatric biobanks are the central focus of this article. We first review the international regulations that apply to biobanks and then summarise viewpoints expressed by experts in a round-table discussion. We confine ourselves here to two normative questions: (1) How much control should children's parents or legal representatives, and later the children themselves, have over the stored materials and data? (2) What should be done if research findings emerge that have serious implications for a child's health? On the basis of international legal standards and the views of experts, involved in paediatric biobanking, we argue that biological material of children may only be stored in a biobank for scientific purposes if parents provide their explicit consent, the child is re-contacted at 16 or 18 years of age to reconsider storage and use of its material, and the biobank maintains a limited policy in disclosure of individual research findings to the child's parents. What is Known: • Increasingly, biological material of children is stored in biobanks for research purposes. • Clear standards on the conditions under which children's cells or tissues may be stored and used are lacking. What is New: • According to experts, storage and use of children's materials should only be allowed if performed in accordance with appropriate consent procedures and feedback policie

Exempting low-risk health and medical research from ethics reviews: Comparing Australia, the United Kingdom, the United States and the Netherlands

Background: Disproportionate regulation of health and medical research contributes to research waste. Better understanding of exemptions of research from ethics review in different jurisdictions may help to guide modification of review processes and reduce research waste. Our aim was to identify examples of low-risk human health and medical research exempt from ethics reviews in Australia, the United Kingdom, the United States and the Netherlands. Methods: We examined documents providing national guidance on research ethics in each country, including those authored by the National Health and Medical Research Council (Australia), National Health Service (United Kingdom), the Office for Human Research Protections (United States) and the Central Committee on Research Involving Humans (the Netherlands). Examples and types of research projects exempt from ethics reviews were identified, and similar examples and types were grouped together. Results: Nine categories of research were exempt from ethics reviews across the four countries; these were existing data or specimen, questionnaire or survey, interview, post-marketing study, evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, audit and service evaluation, and other exemptions. Existing non-identifiable data and specimens were exempt in all countries. Four categories - evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, and audit and service evaluation - were exempted by one country each. The remaining categories were exempted by two or three countries. Conclusions: Examples and types of research exempt from research ethics reviews varied considerably. Given the considerable costs and burdens on researchers and ethics committees, it would be worthwhile to develop and provide clearer guidance on exemptions, illustrated with examples, with transparent underpinning rationales

Next-generation sequencing-based genome diagnostics across clinical genetics centers: Implementation choices and their effects

Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care

Regulating biobanking with children's tissue: a legal analysis and the experts' view

Many current paediatric studies concern relationships between genes and environment and discuss aetiology, treatment and prevention of Mendelian and multifactorial diseases. Many of these studies depend on collection and long-term storage of data and biological material from affected children in biobanks. Stored material is a source of personal information of the donor and his family and could be used in an undesirable context, potentially leading to discrimination and interfering with a child's right to an open future. Here, we address the normative framework regarding biobanking with residual tissue of children, protecting the privacy interests of young biobank donors (0-12 years). We analyse relevant legal documents concerning storage and use of children's material for research purposes. We explore the views of 17 Dutch experts involved in paediatric biobank research and focus on informed consent for donation of leftover tissue as well as disclosure of individual research findings resulting from biobank research. The results of this analysis show that experts have no clear consensus about the appropriate rules for storage of and research with children's material in biobanks. Development of a framework that provides a fair balance between fundamental paediatric research and privacy protection is necessar