生物样本库及其伦理问题简介

随着分子和基因组信息对流行病学影响的增加,无数遗传流行病学研究和后人类基因组计划的研究都越来越依赖人类生物样本库的使用。生物样本库的范围也已横跨学术或者医院环境下的小数量收集到大规模的全国性储藏。尽管生物样本库的概念并不新,但是在基因组研究和后人类基因组计划的背景下,伴随它们十几年极大发展的是无数待解决的伦理挑战。从生物样本库的概念着手,介绍了其与一般遗传数据库的区别以及建立生物样本库的意义;然后介绍并比较国际上已有的生物样本库,以及其伦理问题和伦理法律框架的发展趋势。     

Children and biobanks: a review of the ethical and legal discussion

The use of tissue samples from children is vital to genetic research. Collections of such tissue, in so-called biobanks, can take the form of large-scale prospective cohort studies or disease-specific studies using tissue of children with that specific disease. Collections of samples gathered in a diagnostics context, such as blood spot cards, can also be used for genetic research. Research on stored tissue samples from children poses ethical questions that are different from those posed by the use of samples from adults. Also, the ethical questions raised by the participation of children in biobanks are not analogous to those raised by the participation of children in clinical trials. In this review we first give an overview of the international ethical guidelines and legal regulations concerning biobanking and minors. Next, we review the different themes that occur in the ethical literature on this subject. Specifically we focus on questions of risk and benefit, consent and assent and the return of individual results. We also discuss the concept of solidarity, which is a relatively new concept in the context of children and biomedical research. To conclude, we discuss the gaps and questions raised by the review.     

Closure of population biobanks and direct-to-consumer genetic testing companies

Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss—using population and direct-to-consumer (DTC) genetic testing companies’ biobanks as case studies—(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.     

Biobanking and international interoperability: samples

In terms of sample exchange, international collaborations between biobanks, or between biobanks and their research partners, have two important aspects. First, the donors’ consent usually implies that the scope and purpose of any sample transfer to third parties is subject to major constraints. Since the legal, ethical and political framework of biobanking may differ substantially, even between countries of comparable jurisdictional systems, general rules for the international sharing of biomaterial are difficult, if not impossible, to define. Issues of uncertainty include the right to transfer the material, the scope of research allowed, and intellectual property rights. Since suitable means of international law enforcement may not be available in the context of biobanking, collaborators are advised to clarify any residual uncertainty by means of bilateral contracts, for example, in the form of material transfer agreements. Second, biobank partners may rightly expect that the biomaterial they receive for further analysis attains a certain level of quality. This implies that a biobank has to implement stringent quality control measures covering, in addition to the material transfer itself, the whole process of material acquisition, transport, pre-analytical handling and storage. Again, it may be advisable for biobank partners to claim contractual warranties for the type and quality of the biomaterial they wish to acquire.     

A Proposed Approach to Informed Consent for Biobanks in China

Biobanks are potential goldmines for genomics research. They have become increasingly common as a means to determine the relationship between lifestyle, environmental exposures and predisposition to genetic disease. More and more countries are developing massive national scale biobanks, including Iceland, the UK and Estonia. Now several large‐scale regional and national biobanks are planned in China, such as Shanghai Biobank, which is defined as a key‐element in Shanghai's twelfth five‐year Development Plan of Science and Technology. It is imperative that the authors who are in charge of the ethical aspect of Shanghai Biobank discuss the ethical aspects of these biobanks up front. Currently there is a great deal of heterogeneity in the approaches to informed consent taken by different countries. In the article, after briefly introducing the biobanks in China, we focus on the three most common approaches: classical informed consent, tiered consent, and one‐time general (or blanket) consent, and propose a version of the latter for China, based on compelling arguments.     

Biobanking and public health: is a human rights approach the tie that binds?

Ethical principles guiding public health and genomic medicine are often at odds: whereas public health practice adopts collectivist principles that emphasize population-based benefits, recent advances in genomic and personalized medicine are grounded in an individualist ethic that privileges informed consent, and the balancing of individual risk and benefit. Indeed, the attraction of personalized medicine is the promise it holds out to help individuals get the “right medicine for the right problem at the right time.” Research biobanks are an effective tool in the genomic medicine toolbox. Biobanking in public health presents a unique case study to unpack some of these issues in more detail. For example, there is a long history of using banked tissue obtained under clinical diagnostic conditions for later public health uses. But despite the collectivist approach of public health, the principles applied to the ethical challenges of biobanking (e.g. informed consent, autonomy, privacy) remain individualist. We demonstrate the value of using human rights as a public health ethics framework to address this tension in biobanking by applying it to two illustrative cases.     

Genetic research and consent: On the crossroads of human and data research

This paper explores the legal and ethical concept of human subject research in order to determine whether genetic research with already available biosamples and data falls within this concept. Although the ethical concept seems to have evolved to recognize research based on data as human research, from a supranational legal perspective this form of research is not considered human subject research. Thus human subject research regulations do not apply and therefore do not invoke the requirement of obtaining consent prior to using an individual’s biosample or genetic data in research. Furthermore, it remains ambiguous in both the legal and ethical realm whether the use of biosamples or genetic data without additional links to the individual would invoke the same safeguards as research involving additional or specific identifiers. Seeing that research based on already available biosamples and genetic data is not governed by rules concerning human subject research, the second part of the paper analyses whether any consent requirements apply for the further use of already available bio‐samples or genetic data in research. Whereas further use of biosamples is subject to considerably lax consent requirements under Article 22 of the Oviedo Convention, under the General Data Protection Regulation further use of genetic data might not be subject to a prior consent requirement at all, unless it is stipulated in national laws. When it comes to clinical trials, however, sponsors will have the possibility under Article 28(2) of Regulation 536/2014 to obtain open consent for further use of data in any kind of future research.     

Biobanking and deceased persons

Early biomedical research focused primarily on the study of specific diseases or sets of diseases within small groups of living research participants. Accordingly, the first ethical frameworks governing biomedical research addressed short-term, limited-scope research involving living research participants. Due to recent interest in longitudinal population studies and biobanking, research is increasingly long term. This shift raises several ethical and legal issues concerning the impact of a participant’s death on research. This paper offers an overview of these issues in the context of longitudinal biobanking genetic research. Our first part outlines the legal and ethical frameworks that govern the effect of the participants’ death on consent. This will be followed by an analysis of the legal and ethical frameworks that govern the secondary use of deceased participants’ data and samples and the return of deceased participants’ individual research results to biological family members. In our second part, we will review the current literature and discuss the above mentioned issues using the bioethics “principlism” theory before concluding.     

Biobanken

Biobanks have become an indispensable component of biomedical research. However, the long-term and unrestricted use of data and biomaterials included in most biobanks pose several legal, ethical and organizational challenges. Therefore, the German Telematics Platform for Medical Research Networks (TMF) has instigated a number of projects addressing the problems arising from the establishment and maintenance of biobanks, each time aiming at the provision of generic solutions to the research community in the form of texts and concepts. After a representative review of existing biobanks in Germany and Europe we provide an overview of the TMF work on biobanking. In addition, two infrastructural projects will be reviewed which should render biobanking in Germany and Europe more efficient and transparent in the future, namely the “Biobanking and Biomolecular Resources Research Infrastructure”(BBMRI) of the European Commission and the National Biobank Register that is currently being set up by the TMF.     

Model requirements for Biobank Software Systems

Biobanks are essential tools in diagnostics and therapeutics research and development related to personalized medicine. Several international recommendations, standards and guidelines exist that discuss the legal, ethical, technological, and management requirements of biobanks. Today's biobanks are much more than just collections of biospecimens. They also store a huge amount of data related to biological samples which can be either clinical data or data coming from biochemical experiments. A well-designed biobank software system also provides the possibility of finding associations between stored elements. Modern research biobanks are able to manage multicenter sample collections while fulfilling all requirements of data protection and security. While developing several biobanks and analyzing the data stored in them, our research group recognized the need for a well-organized, easy-to-check requirements guideline that can be used to develop biobank software systems. International best practices along with relevant ICT standards were integrated into a comprehensive guideline: The Model Requirements for the Management of Biological Repositories (BioReq), which covers the full range of activities related to biobank development. The guideline is freely available on the Internet for the research community. AVAILABILITY: The database is available for free at http://bioreq.astridbio.com/bioreq_v2.0.pdf.     

‘It is an entrustment’: Broad consent for genomic research and biobanks in sub‐Saharan Africa

In recent years, there has been an increase in the establishment of biobanks for genetic and genomic studies around the globe. One example of this is the Human Heredity and Health in Africa Initiative (H3Africa), which has established biobanks in the sub‐region to facilitate future indigenous genomic studies. The concept of ‘broad consent’ has been proposed as a mechanism to enable potential research participants in biobanks to give permission for their samples to be used in future research studies. However, questions remain about the acceptability of this model of consent. Drawing on findings from empirical research about the role of trust in decision‐making, we argue that an account of entrustment may be an appropriate way of addressing current challenges of seeking consent for biobank research in Africa. We propose a set of key points to consider that can support the proposed entrustment framework.     

The role and responsibilities of witnesses in the informed consent process

Various mechanisms to ensure the protection of subjects in human research have been suggested, including the presence of witnesses during the informed consent process. For our commentary on the use of witnesses and their potential role and responsibility during the consent process, we start by addressing current guidelines for human subjects research in four Latin American countries. By using examples from public health research, we highlight some of the practical difficulties of using witnessed consent, from becoming a meaningless ritual at one end of the spectrum to the research subject feeling intimidated or coerced to participate at the other. Apart from these practical difficulties, it is unclear what responsibility the witness could and should have. We argue that there are important ethical questions about the role of witnesses that have not been adequately addressed in national and international regulations. This work addresses these gaps and argues that more debate is required to define the role and responsibilities of witnesses in the consent process, their training requirements and whether a universal legal requirement for witnessed consent, regardless of the type of research, is desirable.     

Best Practice Guidelines on Informed Consent for Weight Loss Surgery Patients

Objective: To provide evidence‐based guidelines on informed consent and the education that underlies it for legally competent, severely obese weight loss surgery (WLS) patients. Research Methods and Procedures: We conducted a systematic review of the scientific literature published on MEDLINE between 1984 and 2004. Three articles focused on informed consent for WLS; none was based on empirical studies. We summarized each paper and assigned evidence categories according to a grading system derived from established evidence‐based models. We also relied on informed consent and educational materials from six WLS programs in Massachusetts. All evidence is Category D. Recommendations were based on a review of the available literature, informed consent materials from WLS programs, and expert opinion. Results: This Task Group found that the informed consent process contributes to long‐term outcome in multiple ways but is governed by limited legal requirements. We focused our report on the legal and ethical issues related to informed consent, i.e., disclosure vs. comprehension. Recommendations centered on the importance of assessing patient comprehension of informed consent materials, the content of those materials, and the use of active teaching/learning techniques to promote understanding. Discussion: Although demonstrated comprehension is not a legal requirement for informed consent in Massachusetts or other states, the members of this Task Group found that the best interests of WLS patients, providers, and facilities are served when clinicians engage patients in active learning and collaborative decision making.     

Biobanks for life sciences and personalized medicine: importance of standardization,biosafety, biosecurity,and data management

Biological samples such as tissues, blood and other body fluids, plants or seeds, prokaryotic and eukaryotic cells or isolated biomolecules as well as associated data are the essential raw material for research and development in medicine, biotechnology and agriculture. The collection, processing, preservation, and storage of these resources, in addition to provision of access, are key activities of biobanks or biological resource centres. Biobanks have to ensure proper quality of samples and data, ethical and legal compliance as well as transparent and efficient access procedures. In this context the review places special emphasis on pre-analytical procedures and international standards, which are essential to improving analytical data reliability and reproducibility, as well as on the increasing importance of data management. These requirements of biobanks are demonstrated using the example of pathogen-containing and microbiome biobanks, and refer to needs in cancer research and development.     

"Who owns your poop?": insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies

Background

While the social, ethical, and legal implications of biobanking and large scale data sharing are already complicated enough, they may be further compounded by research on the human microbiome.

Discussion

The human microbiome is the entire complement of microorganisms that exists in and on every human body. Currently most biobanks focus primarily on human tissues and/or associated data (e.g. health records). Accordingly, most discussions in the social sciences and humanities on these issues are focused (appropriately so) on the implications of biobanks and sharing data derived from human tissues. However, rapid advances in human microbiome research involve collecting large amounts of data on microorganisms that exist in symbiotic relationships with the human body. Currently it is not clear whether these microorganisms should be considered part of or separate from the human body. Arguments can be made for both, but ultimately it seems that the dichotomy of human versus non-human and self versus non-self inevitably breaks down in this context. This situation has the potential to add further complications to debates on biobanking.

Summary

In this paper, we revisit some of the core problem areas of privacy, consent, ownership, return of results, governance, and benefit sharing, and consider how they might be impacted upon by human microbiome research. Some of the issues discussed also have relevance to other forms of microbial research. Discussion of these themes is guided by conceptual analysis of microbiome research and interviews with leading Canadian scientists in the field.

     

Alternative consent models for biobanks: the new Spanish law on biomedical research

This article provides an overview of recent contributions to the debate on the ethical use of previously collected biobank samples, as well as a country report about how this issue has been regulated in Spain by means of the new Biomedical Research Act, enacted in the summer of 2007. By contrasting the Spanish legal situation with the wider discourse of international bioethics, we identify and discuss a general trend moving from the traditional requirements of informed consent towards new models more favourable to research in a post-genomic context.     

Ethical obligation and legal requirements: On informed consent practices in Bangladesh

Informed consent to medical intervention is fundamental in both ethics and law. But in practice it is often not taken seriously in developing countries. This paper provides an appraisal of informed consent practices in Bangladesh. Following a review of the ethical and legal principles of informed consent, it assesses the degree to which doctors adhere to it in Bangladesh. Based on findings of non-compliance, it then investigates the reasons for such non-compliance through an appraisal of informed consent practices in Bangladesh and provides recommendations aimed at improving such practices. The significance of this paper lies in unveiling the interdependence between the ethical and legal traits of informed consent and their ramifications on strengthening the patient-oriented approach of duty to care.     

Population biobanking in selected European countries and proposed model for a Polish national DNA bank

Population biobanks offer new opportunities for public health, are rudimentary for the development of its new branch called Public Health Genomics, and are important for translational research. This article presents organizational models of population biobanks in selected European countries. Review of bibliography and websites of European population biobanks (UK, Spain, Estonia). Some countries establish national genomic biobanks (DNA banks) in order to conduct research on new methods of prevention, diagnosis and treatment of the genetic and lifestyle diseases and on pharmacogenetic research. Individual countries have developed different organizational models of these institutions and specific legal regulations regarding various ways of obtaining genetic data from the inhabitants, donors’ rights, organizational and legal aspects. Population biobanks in European countries were funded in different manners. In light of these solutions, the authors discuss prospects of establishing a Polish national genomic biobank for research purpose. They propose the creation of such an institution based on the existing network of blood-donation centres and clinical biobanks in Poland.     

Biobank resources for future patient care: developments, principles and concepts

The aim of the overview is to give a perspective of global biobank development is given in a view of positioning biobanking as a key resource for healthcare to identify new potential markers that can be used in patient diagnosis and complement the targeted personalized drug treatment. The fast progression of biobanks around the world is becoming an important resource for society where the patient benefit is in the focus, with a high degree of personal integrity and ethical standard. Biobanks are providing patient benefits by large scale screening studies, generating large database repositories. It is envisioned by all participating stakeholders that the biobank initiatives will become the future gateway to discover new frontiers within life science and patient care. There is a great importance of biobank establishment globally, as biobanks has been identified as a key area for development in order to speed up the discovery and development of new drugs and protein biomarker diagnostics. One of the major objectives in Europe is to establish concerted actions, where biobank networks are being developed in order to combine and have the opportunity to share and build new science and understanding from complex disease biology. These networks are currently building bridges to facilitate the establishments of best practice and standardizations.     

Closing the gaps in genetics legislation and policy: a report by the new york state task force on life and the law

The New York State Task Force on Life and the Law, a state bioethical policy commission, recently completed a project addressing the ethical, legal, and social concerns surrounding the predictive uses of genetic testing. Its report, Genetic Testing and Screening in the Age of Genomic Medicine, makes legislative, public policy, and practice recommendations on a host of issues. As part of this project, the Task Force reviewed the current policy and legislative landscapes related to confidentiality protections for genetic information and the use of genetic information by insurers. It also assessed requirements for informed consent to clinical genetic testing and for the use of clinical samples for genetics research. The Task Force considered gaps and unintended consequences of relevant genetic testing legislation and assessed its flexibility to address new uses of genetic testing, such as pharmacogenetic testing, and new ways of offering tests, such as multiplex testing panels. The Task Force also considered the relevance of the pleiotropic characteristic of genes for issues of informed consent to genetic testing and the confidentiality of genetic information. The Task Force's recommendations, presented here, seek to promote the appropriate uses of clinical genetic testing and research while preventing potential harms.