A legal framework for biobanking: the German experience

Although biobanks are vital for modern medical research, serious concerns have been raised about the legal basis and framework of such endeavours. This led the German 'Telematics Platform for Medical Research Networks' ('Telematikplattform für Medizinische Forschungsnetze', TMF) to initiate a project in 2004 that was designed to place German biobanks on a sound legal footing. This project involved the planning, writing and evaluation of an expert report that addresses in great detail the legal issues concerning property rights, medical professional regulations, general liability insurance, resource continuity and research secrecy. Here, we provide a brief summary of the major results of this project.     

Practical implementation issues and challenges for biobanks in the return of individual research results

Whether or not to give research results back to individuals whose specimens are used for biomedical research is a subject of considerable controversy. Much of the debate has been focused around the ethical and legal concerns with some consideration of broader social issues such as whether or not people will be affected by such information for employment or health care. Much less attention has been paid to biobanks that collect the specimens used to generate the research findings and the issues and operational requirements for implementing return of individual research results. In this article, we give the biobanks’ perspective and highlight that given the diversity among the types of biobanks, it may be difficult to design and implement a blanket policy in this complex area. We discuss the variability in the types of biobanks and some important issues that should be considered in determining whether or not research results should be provided to individuals whose specimens are used in biomedical research. We also discuss challenges that should be considered in implementing any approaches to the return of research results.Genet Med 2012:14(4):478–483     

Retrospective access to data: the ENGAGE consent experience

The rapid emergence of large-scale genetic databases raises issues at the nexus of medical law and ethics, as well as the need, at both national and international levels, for an appropriate and effective framework for their governance. This is even more so for retrospective access to data for secondary uses, wherein the original consent did not foresee such use. The first part of this paper provides a brief historical overview of the ethical and legal frameworks governing consent issues in biobanking generally, before turning to the secondary use of retrospective data in epidemiological biobanks. Such use raises particularly complex issues when (1) the original consent provided is restricted; (2) the minor research subject reaches legal age; (3) the research subject dies; or (4) samples and data were obtained during medical care. Our analysis demonstrates the inconclusive, and even contradictory, nature of guidelines and confirms the current lack of compatible regulations. The second part of this paper uses the European Network for Genetic and Genomic Epidemiology (ENGAGE Consortium) as a case study to illustrate the challenges of research using previously collected data sets in Europe. Our study of 52 ENGAGE consent forms and information documents shows that a broad range of mechanisms were developed to enable secondary use of the data that are part of the ENGAGE Consortium.     

The policies of ethics committees in the management of biobanks used for research: an Italian survey

Gaps in regulations pertaining to the collection and storage of biological materials in a biobank, at least in the European context, have made the writing of local guidelines essential from an ethical point of view. Nevertheless, until recently, the elaboration of local guidelines for the collection, use and storage of biological materials in a biobank has been the exception in Italy and all European countries. In this context, it is of value to know the policies, even if they are unwritten, of local ethics committees (ECs) engaged in the evaluation of research protocols involving biobanks and biological materials. This paper presents the results of a survey carried out among local Italian ECs (229) to document their attitudes and policies regarding the management of the ethical issues related to biobanks and the use of biological materials. A questionnaire was developed to investigate the areas regarded as critical from an ethical–legal point of view: informed consent and information to the subjects; protection of confidentiality; communication of research results; access/transfer of biological materials and related data; ownership of samples and data and intellectual property rights; and subjects'' remuneration and benefit sharing. Twenty-six ECs from the Italian Institutes for Research and Care (62%) and 26 other ECs (14%) participated in the survey.     

Ethical aspects of human biobanks: a systematic review

Aim

To systematically assess the existing literature on ethical aspects of human biobanks.

Method

We searched the Web of Science and PubMed databases to find studies addressing ethical problems in biobanks with no limits set (study design, study population, time period, or language of publication). All identified articles published until November 2010 were included. We analyzed the type of published articles, journals publishing them, involvement of countries/institutions, year of publication, and citations received, and qualitatively assessed every article in order to identify ethical issues addressed by the majority of published research on human biobanking.

Results

Hundred and fifty four studies satisfied our review criteria. The studies mainly came from highly developed countries and were all published in the last two decades, with over half of them published in 2009 or 2010. They most commonly discussed the informed consent, privacy and identifiability, return of results to participants, importance of public trust, involvement of children, commercialization, the role of ethics boards, international data exchange, ownership of samples, and benefit sharing.

Conclusions

The focus on ethical aspects is strongly present through the whole biobanking research field. Although there is a consensus on the old and most typical ethical issues, with further development of the field and increasingly complex structure of human biobanks, these issues will likely continue to arise and accumulate, hence requiring constant re-appraisal and continuing discussion.Biobanks comprise organized collections of human biological samples, usually associated personal health information, which are used together for biomedical research. Research results are generally very important for the society and biobanks have been heavily supported by many governments. Thus, in the recent few years biobanks have undergone rapid proliferation and have become increasingly complex. Their complexity has arisen from an increasingly diverse set of research purposes, and of types and sources of the samples. For instance, biobanks could comprise the collections of human bodily substances of all kinds, such as cells, tissues, blood, or DNA. They range in capacity from small collections of samples to large-scale national repositories. The collected samples could be population-based or disease-specific, originating from diverse profile of individuals, eg, minors or adult persons. Biobanks may contain anonymous human samples or samples linked to the specific personal information. Also, there are various purposes of biobanks, such as diagnostic, therapeutic, or research. Biobanks could be an ownership of public or private subjects, the latter being non-profit or profit based. As a consequence, such a diversity of biobanking is associated with a broad spectrum of ethical and legal issues (1-5).Ethical issues are commonly present in many aspects of biobanking. The fact that biobanks deal with human samples, invading an individual autonomy or limiting self-control, provokes a number of ethical issues. Who is actually competent to give informed consent and donate a sample? When individuals donate part of their body to a biobank, how is that human sample processed? Who is the owner of the sample? Who should decide how it should be used? Who has the right to know individual results of research? These and many more ethical dilemmas exist in the ethical framework of biobanks. With the recent rapid developments in biobanking, all of these issues are magnified with plenty of further new questions continuously arising. Ethical framework has been the most controversial issue in the domain of biobanking. Thus, it is not surprising that there is a substantial literature focusing on ethical dilemas in biobanking, such as informed consent, privacy, protection, and returning of results to participants (6-9).Due to these reasons, it is very important that researchers are provided with a current review of the literature on the ethics of biobanking in a systematic way, to document the latest consensus on ethical issues in biobanking and to highlight emerging issues. For that purpose, we reviewed the existing literature on ethical aspects of human biobanks. We aimed to develop a systematic framework for categorizing ethical concerns relevant to human biobanks and to monitor the impact of research into ethical issues. This could help the ethical boards in decision making when dealing with issues within the framework of biobanking. Moreover, we believe that such kind of work could stimulate policymakers and lawmakers to create an adequate legal framework for biobanking, an important, but still largely unregulated issue.     

Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Implications for pathology

High quality human biological samples (e.g. blood, tissue or DNA) with associated, well documented clinical and research data are key resources for advancement of life sciences, biotechnology, clinical medicine, drug development and also molecular pathology. Millions of samples of diseased tissues have been collected in the context of routine histopathological diagnosis and are stored in the archives of hospitals and institutes of pathology. A concerted effort is necessary to overcome the current fragmentation of the European biobanking community in order to tap the full research potential of existing biobanks. A pan-European research infrastructure for biobanking and biomolecular resources (BBMRI) is currently in its planning phase. The mission is to link and provide access to local biobanks of different formats, including tissue collections, harmonize standards, establish operational procedures which properly consider ethical, legal, societal aspects, and to secure sustainable funding. Pathology plays a key role in development and administration of tissue banks and is, thus, a major partner for collaboration, expertise and construction of this pan-European research infrastructure.     

The legal risks of returning results of genomics research

Published guidelines suggest that research results and incidental findings should be offered to study participants under some circumstances. Although some have argued against the return of results in research, many cite an emerging consensus that there is an ethical obligation to return at least some results; the debate quickly turns to issues of mechanics (e.g., which results? who discloses? for how long does the obligation exist?). Although commentators are careful to distinguish this as an ethical rather than legal obligation, we worry that return of results may unjustifiably become standard of care based on this growing “consensus,” which could quickly lead to a legal (negligence-based) duty to offer and return individualized genetic research results. We caution against this and argue in this essay that the debate to date has failed to give adequate weight to a number of fundamental ethical and policy issues that should undergird policy on return of research results in the first instance, many of which go to the fundamental differences between research and clinical care. We confine our comments to research using data from large biobanks, the topic of the guidelines proposed in this symposium issue.Genet Med 2012:14(4):473–477     

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 necessary.     

Improving the informed consent process in international collaborative rare disease research: effective consent for effective research

The increased international sharing of data in research consortia and the introduction of new technologies for sequencing challenge the informed consent (IC) process, adding complexities that require coordination between research centres worldwide. Rare disease consortia present special challenges since available data and samples may be very limited. Thus, it is especially relevant to ensure the best use of available resources but at the same time protect patients'' right to integrity. To achieve this aim, there is an ethical duty to plan in advance the best possible consent procedure in order to address possible ethical and legal hurdles that could hamper research in the future. Therefore, it is especially important to identify key core elements (CEs) to be addressed in the IC documents for international collaborative research in two different situations: (1) new research collections (biobanks and registries) for which information documents can be created according to current guidelines and (2) established collections obtained without IC or with a previous consent that does not cover all CEs. We propose here a strategy to deal with consent in these situations. The principles have been applied and are in current practice within the RD-Connect consortia – a global research infrastructure funded by the European Commission Seventh Framework program but forward looking in terms of issues addressed. However, the principles established, the lessons learned and the implications for future research are of direct relevance to all internationally collaborative rare-disease projects.     

Do we need a uniform regulatory system for biobanks across Europe?

Within Europe, there is currently no uniform regulatory system that applies to human biobanks used for genetic research purposes. This has resulted in considerable variation in the national law that applies to the use of DNA samples, personal information and medical records in the countries across Europe. This could result in a situation where researchers collaborating across Europe may be operating unlawfully if they share research data and samples across borders where different laws are in operation. There are also concerns that the lack of standardised guidelines inhibits cooperation among researchers across Europe but also restricts the sharing of DNA samples and information across national borders, which is problematic for multinational companies and institutions carrying out collaborative research. Ultimately, the lack of a uniform regulatory system may have implications for the viability and long-term competitiveness of collaborative European research. The purpose of this paper is to discuss some of the preliminary issues that would need to be considered before such a regulatory system for biobanks could be developed within Europe.     

An empirical examination of the management of return of individual research results and incidental findings in genomic biobanks

PurposeThe purpose of this study was to examine and document the management and return of individual research results and incidental findings to research participants among biobanks.MethodsA comprehensive Internet search was completed to identify biobanks and collect available documents about biobanks and their procedures and policies regarding the return of results. The Internet search was supplemented by an e-mail request to gather further such documents. A total of 2,366 documents were collected for analysis from a sample of 85 biobanks.ResultsThe major finding of this empirical work is that the majority of the biobanks in the sample do not address the return of individual research results and incidental findings in their publicly available documents.ConclusionThe results suggest that there is a need for more discussion and guidance about the most appropriate ways for biobanks to consider the return of individual research results and incidental findings and generate policies and procedures that address this issue.Genet Med 2012:14(4):444–450     

Evaluation of biobank constitution and use: multicentre analysis in France and propositions for formalising the activities of research ethics committees

Biobanks are collections of biological material and related files gathered and stored for clinical or research purposes. Here, we investigated the questions raised during the evaluation of biobanks by biomedical Research Ethics Committees (RECs), particularly in the context of genetic research. We sent a questionnaire to all RECs in France to survey their concerns and the ethical criteria used when evaluating research involving the storage of biological samples. Most of the RECs think that they should be consulted to evaluate the constitution of biobanks. The proportion of RECs of this opinion depended on whether the biobank is being constituted in the absence of an associated research project (initially created for clinical purposes or for undefined research) (14/28), whether the biobank is being constituted for research use (21/28) or whether an existing research biobank is being re-used (19/28). Views diverged concerning the way ethics principles are applied, showing that REC evaluations of biobanks might be formalised at each of the following steps: constitution, use and re-use. In this paper, we suggest concrete elements that could be integrated into the application of the new French law concerning the protection of the human beings participating in research as well as into international recommendations.     

International normative perspectives on the return of individual research results and incidental findings in genomic biobanks

Managers of genomic biobanks constantly face ethical and legal challenges ranging from issues associated with the informed consent process to procedural concerns related to access by researchers. Yet, with the availability of next-generation sequencing technologies, one topic is emerging as the focus of ongoing debate: the return of individual research results and incidental findings to participants. This article examines this topic from an international perspective, where policies and guidelines discussing the matter in the context of genomic biobanks and genomic research are analyzed and commented. This approach aims to highlight the shortcomings of these international norms, mainly the danger arising from both the therapeutic misconception and the conflation of research results with incidental findings. This article suggests some elements to consider in order to complement available guidance at the international level.Genet Med 2012:14(4):484–489     

Managing incidental findings and research results in genomic research involving biobanks and archived data sets

Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using “biobank” here to refer both to collections of samples and collections of data). This article reports recommendations from a 2-year project funded by the National Institutes of Health. We analyze the responsibilities involved in managing the return of incidental findings and individual research results in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). We suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When reidentification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities to (1) clarify the criteria for evaluating findings and the roster of returnable findings, (2) analyze a particular finding in relation to this, (3) reidentify the individual contributor, and (4) recontact the contributor to offer the finding. We suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and are clinically actionable should generally be offered to consenting contributors. This article specifies 10 concrete recommendations, addressing new biobanks as well as those already in existence.Genet Med 2012:14(4):361–384     

Les biobanques en immunoanalyse et biologie spécialisée

Human sample biobanks are isolated or network infrastructures, collecting, preparing, aliquoting, cryopreserving and managing biological resources for biomedical research purposes. Biobanks are situated at the interface between the clinical facility where biospecimens are sampled and the Research Laboratory where samples are analysed. Biobanks arise many political, legal–ethical and technical questions.     

Public’s attitudes on participation in a biobank for research: an Italian survey

Background

The creation of biobanks depends upon people’s willingness to donate their samples for research purposes and to agree to sample storage. Moreover, biobanks are a public good that requires active participation by all interested stakeholders at every stage of development. Therefore, knowing public’s attitudes towards participation in a biobank and biobank management is important and deserves investigation.

Method

A survey was conducted among family members of patients attending the outpatient department of our institute for a geriatric or neurological visit, documenting their willingness to participate in a biobank and their views on the legal-ethical aspects of biobank management. Information regarding subjects’ attitudes on biomedical research in general and genetic research in particular was also collected. Participants’ data on biobanks were compared with data previously collected from the Italian ethics committees (ECs) to evaluate the extent to which lay people and ethics committees share views and concerns regarding biobanks.

Results

One hundred forty-five subjects took part in the survey. The willingness to give biological samples for the constitution of a biobank set up for research purposes was declared by 86% of subjects and was modulated by subjects’ education. People in favour of providing biological samples for a biobank expressed a more positive view on biomedical research than did people who were not in favour; attitude towards genetic research in dementia was the strongest predictor of participation. Different from ECs that prefer specific consent (52%) and do not choose the option of broad consent (8%) for samples collection in a biobank, participants show a clear preference for broad consent (57%), followed by partially restricted consent (16%), specific consent (15%), and multi-layered consent (12%). Almost all of the subjects available to contribute to a biobank desire to receive both individual research results and research results of general value, while around fifty per cent of ECs require results communication.

Conclusion

Family members showed willingness to participate in a biobank for research and expressed a view on the ethical aspects of a biobank management that differ on several issues from the Italian ECs’ opinion. Laypersons’ views should be taken into account in developing biobank regulations.

     

A biobank management model applicable to biomedical research

Background  

The work of Research Ethics Boards (REBs), especially when involving genetics research and biobanks, has become more challenging with the growth of biotechnology and biomedical research. Some REBs have even rejected research projects where the use of a biobank with coded samples was an integral part of the study, the greatest fear being the lack of participant protection and uncontrolled use of biological samples or related genetic data. The risks of discrimination and stigmatization are a recurrent issue. In light of the increasing interest in biomedical research and the resulting benefits to the health of participants, it is imperative that practical solutions be found to the problems associated with the management of biobanks: namely, protecting the integrity of the research participants, as well as guaranteeing the security and confidentiality of the participant's information.     

低温保存对生物样本及其生物大分子的影响

生物样本库在现代医学研究中的作用日趋重要,基于生物样本库的研究成果层出不穷,极大地推动转化医学的发展。生物样本库中样本保存的质量对研究结果的可靠性有较大影响,如何保存高质量的样本是生物样本库研究的关键问题之一。低温保存技术可以保持样本的活性,若将其用于生物样本库,不仅能够保存样本完整的分子信息,还能保持样本的活性,对生物样本库的发展具有里程碑式的意义。综述低温保存方法对样本的损伤(尤其是生物大分子的损伤)以及减小这些损伤的技术与方法,为提高生物样本的保存质量提供指导性建议。     

Biobank research and ethics: the problem of informed consent in Polish biobanks

Introduction

The dynamic development of biobanks causes some ethical, social, and legal problems. The most discussed problems are obtaining informed consent, especially for future research, from minors and from deceased people. The aim of this article is to present the current standards held by Polish biobanks concerning obtaining a participant''s informed consent in some aspects.

Material and methods

Survey was carried out by anonymous questionnaire among 59 institutions which deal with the collecting and storage of human cells and tissues in the year 2008. Twenty four filled-in copies of the questionnaires were sent back (return=41%).

Results

Almost every institution (92%) obtains written consent, but a third of the surveyed institutions (29%) do not obtain consent for the future use of the samples. The majority of the respondents (83%) support the idea of using biological materials for research purposes of a donor who died if he did not leave any written objection to such practices and 46% of respondents stated that biobanks should obtain the consent from the already mature donor who gave their samples as a child.

Conclusions

The practice and rules for obtaining informed consent for the scientific research require improvement. The possibility to use the human materials in the future, conditions for getting access to the data, the possibility of their withdrawal from the database and using the materials and data after the death of the donor should be clearly determined when the informed consent to collect the material is obtained.