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.     

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     

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.     

Experience with establishment and operation of a biobank

Tissue specimens taken in pathology for diagnostic or therapeutic interventions have been collected for decades, archived and used for local research projects. Meanwhile there is an increasing need of this material for academic and non-academic biomedical research. Many questions in the field of translational research can only be addressed with a sufficient number of high quality tissue samples especially when combined with comprehensive clinical data. Although biobanks represent an indispensable basis for medical research, this might be in conflict with the rights of patients. Currently there are no specific regulations for biobanks leading to substantial legal uncertainties. However, interpretation of existing regulations by the National Ethics Committee or the Telematic Platform for Medical Research Network are important for ethical and legal solutions. Irrespective of future (national or European) regulations, the informed consent of the patients including a secure data protection concept is a prerequisite for establishment and operation of biobanks.     

Feedback of individual genetic results to research participants: in favor of a qualified disclosure policy

This article discusses whether and when researchers have a moral obligation to feedback individual genetic research results. This unsettled debate has rapidly gained in urgency in view of the emergence of biobanks and the advances in next-generation sequencing technology, which has the potential to generate unequalled amounts of genetic data. This implies that the generation of many known and unknown genetic variants in individual participants of genetics/genomics research as intentionally or collaterally obtained byproducts is unavoidable. As we conclude that valid reasons exist to adopt a duty to return genetic research results, a qualified disclosure policy is proposed. This policy contains a standard default package, possibly supplemented with (one or more of) three additional packages. Whereas the default package, containing life-saving information of immediate clinical utility, should be offered routinely and mandatory to all research participants, offering (one of) the three additional packages is context-specific. Such a qualified disclosure policy in our opinion best balances the potential benefits of disclosure with the potential risks for research participants and the harms of unduly hindering biomedical research. We appeal to the genetics community to make a joint effort to further refine the packages and set thresholds for result selection.     

Mapping the inputs,analyses, and outputs of biobank research systems to identify sources of incidental findings and individual research results for potential return to participants

Progress in the debate over returning incidental findings (IFs) and individual research results (IRRs) to research participants who provide specimens and data to biobanks in genetic and genomic research requires a new tool to allow comparison across heterogeneous biobank research systems and in-depth analysis of the sources and types of findings generated for potential return. This article presents a new visual mapping tool to allow systematic and standardized depiction of (i) the specimens initially collected, (ii) the materials and data sets then created, (iii) the analyses then performed, and finally (iv) the genetic and genomic results generated, including potential IFs and IRRs. For any individual biobank research system, this sequence of four maps can be created to anticipate the sources and types of IFs and IRRs to be generated, to plan how to handle them, and then to manage them responsibly over time. We discuss how this four-map tool was created and describe its application to four national biobank systems, thereby demonstrating that this tool can provide a common platform to visualize biobank content, anticipate how IFs and IRRs will arise in a biobank research context, and inform policy development.Genet Med 2012:14(4):385–392     

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     

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     

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.

     

Changing perspectives in biobank research: from individual rights to concerns about public health regarding the return of results

During the past decade, various guidelines that imply a duty for researchers to disclose information obtained through research to participants have emerged. The character and extent of this obligation have been debated extensively, with much attention devoted to the decisiveness of the validity and utility of the results in question. The aim of this paper is to argue that individual results from research on materials stored in large-scale biobanks, consisting of samples taken within the healthcare system or of altruistically donated materials, should not be returned. We will defend the thesis that medical research on these biobanks should be viewed as a collective project to improve public health, and that available resources should be utilized to pursue this goal. We argue that there is a need for a change of perspectives. Medical research should not primarily be viewed as a danger that individuals must be protected from, but rather be recognized as constituting a necessary defense against current and future diseases. Research that bears the prospect of advancing medicine and that can be carried out at no risk to individuals should be endorsed and facilitated. This calls for a shift of focus from autonomy and individual rights toward collective responsibility and solidarity.     

Processes and factors involved in decisions regarding return of incidental genomic findings in research

PurposeStudies have begun exploring whether researchers should return incidental findings in genomic studies, and if so, which findings should be returned; however, how researchers make these decisions—the processes and factors involved—has remained largely unexplored.MethodsWe interviewed 28 genomics researchers in-depth about their experiences and views concerning the return of incidental findings.ResultsResearchers often struggle with questions concerning which incidental findings to return and how to make those decisions. Multiple factors shape their views, including information about the gene variant (e.g., pathogenicity and disease characteristics), concerns about participants’ well-being and researcher responsibility, and input from external entities. Researchers weigh the evidence, yet they face conflicting pressures, with relevant data frequently being unavailable. Researchers vary in who they believe should decide: participants, principal investigators, institutional review boards, and/or professional organizations. Contextual factors can influence these decisions, including policies governing return of results by institutions and biobanks and the study design. Researchers vary in desires for: guidance from institutions and professional organizations, changes to current institutional processes, and community-wide genetics education.ConclusionThese data, the first to examine the processes by which researchers make decisions regarding the return of genetic incidental findings, highlight several complexities involved and have important implications for future genetics research, policy, and examinations of these issues.Genet Med 2014:16(4):311–317.     

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。     

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     

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.     

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.     

Personalized assent for pediatric biobanks

Pediatric biobanking is considered important for generating biomedical knowledge and improving (pediatric) health care. However, the inclusion of children’s samples in biobanks involves specific ethical issues. One of the main concerns is how to appropriately engage children in the consent procedure. We suggest that children should be involved through a personalized assent procedure, which means that both the content and the process of assent are adjusted to the individual child. In this paper we provide guidance on how to put personalized assent into pediatric biobanking practice and consider both the content and process of personalized assent. In the discussion we argue that the assent procedure itself is formative. Investing in the procedure should be a requirement for pediatric biobank research. Although personalized assent will require certain efforts, the pediatric (biobank) community must be aware of its importance. The investment and trust earned can result in ongoing engagement, important longitudinal information, and stability in/for the research infrastructure, as well as increased knowledge among its participants about research activity. Implementing personalized assent will both respect the child and support biobank research.     

Great Expectations: Autism Spectrum Disorder and Induced Pluripotent Stem Cell Technologies

New applications of iPSC technology to research on complex idiopathic conditions raise several important ethical and social considerations for potential research participants and their families. In this short review, we examine these issues through the lens of emerging research on autism spectrum disorder (ASD). We begin by describing the current state of iPSC technology in research on ASD. Then we discuss how the social history of and current controversies in autism research combined with the emergence of autism-specific iPSC biobanks indicate an urgent need for researchers to clearly communicate the limitations and possibilities of iPSC research to ensure research participants have the ability to provide fully informed, voluntary consent. We conclude by offering recommendations to bolster informed consent for research involving iPSC biobanks, both in the specific context of ASD and more broadly.     

Return of individual research results and incidental findings in the clinical trials cooperative group setting

The National Cancer Institute (NCI)-funded cooperative group cancer clinical trial system develops experimental therapies and often collects samples from patients for correlative research. The cooperative group bank (CGB) system maintains biobanks with a current policy not to return research results to individuals. An online survey was created, and 10 directors of CGBs completed the surveys asking about understanding and attitudes in changing policies to consider return of incidental findings (IFs) and individual research results (IRRs) of health significance. The potential impact of the 10 consensus recommendations of Wolf et al. presented in this issue are examined. Reidentification of samples is often not problematic; however, changes to the current banking and clinical trial systems would require significant effort to fulfill an obligation of recontact of subjects. Additional resources, as well as a national advisory board would be required to standardize implementation.Genet Med 2012:14(4):411–416     

Mise en place d’indicateurs de suivi au sein d’une tumorothèque et/ou d’un centre de ressources biologiques : pourquoi et comment ?

The biobanking area is highly complex, and its complexity is increasing along with its growth and demand. Due to the advancements in genetic research, stem cell research and regenerative medicine, biobanking has become ever more important and plays a key role in biomedical research. The robustness and the reproducibility of research results depend greatly on the quality and on the number of the samples used, and thus on the expertise of biobanks having supplied these samples. Undoubtedly, the recognition of a research biobank depends on the impact of the research projects conducted with samples obtained from tumour bank(s), but also on many other criteria. It thus seems important to determine a number of indicators within a biobank to estimate objective criteria for the performance of these structures. These indicators can allow to make some strategic decisions knowing that biobanks are expensive structures to maintain in the present hospital context. The use of these indicators could also contribute to the elaboration of an "biobank impact factor of" or so called "bioresource research impact factor" (BRIF). We describe here four major categories of indicators (quality, activity, scientific production, visibility), which seem to be useful for the evaluation of a biobank by making a proposition of allocation of coefficients for the various considered items.