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     

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     

Clarifying assent in pediatric research

Assent is a relatively young term in research ethics, but became an often mentioned ethical requirement in current pediatric research guidelines. Also, the European Society of Human Genetics considers assent an important condition for the inclusion of children in biobanks. However, although many emphasize the importance of assent, few explain how they understand the concept and few have elaborated on the underlying grounds. In this paper, we will discuss the different underlying ethical principles of assent. In the first category, assent appears to be derived from informed consent. This understanding is grounded in respect for autonomy and protection against harm. We conclude that this interpretation of assent is not of added value as a majority of children cannot be considered competent to make autonomous decisions. In addition, other safeguards are more appropriate to protect children against harm. The grounds from the second category can be classified as engagement grounds. These grounds do justice to the specifics of childhood and are of added value. Furthermore, we argue that it follows that both the content and the process of assent should be adjusted to the individual child. This can be referred to as personalized assent. Personalized assent is an appeal to the moral responsibility and integrity of the researcher.     

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     

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.     

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     

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.     

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.     

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.     

Genetic knowledge and moral responsibility: ambiguity at the interface of genetic research and clinical practice

Despite a rapidly expanding literature on the issue of duty to warn at-risk relatives in the context of clinical genetic testing, little has been written on parallel issues with regard to the management of genetic research results. Some might view this lack as an indication that there is little to discuss in this regard. That is, standard practice is that data obtained through medical research should not be treated as though they are clinically relevant, and this standard should hold for genetic research as well. This paper challenges this conclusion and its underlying assumptions. We argue that the line between genetic research and clinical practice is often ambiguous. In some cases, research data gathered from a very small number of subjects could have immediate clinical implications. Hence, it is unethical for genetic researchers to absolve themselves of clinical responsibilities for research subjects and/or their families, on the grounds that the data were obtained for research purposes. Indeed, we argue that it could well be unethical to embark on some forms of genetic research unless advance arrangements have been made for genetic counseling and clinical follow-up. Furthermore, in some cases, it might be unethical to enroll subjects in studies if the subjects are unwilling to receive their individual results.     

National population-based biobanks for genetic research.

Clinical practice guidelines derived from genetic research using population-based biobanks could dramatically change the nature of personal and public health medicine. Centralized population-based biobanks have been established or proposed in at least nine countries to date, and many lessons have been learned from these landmark developments. Scientific and governmental leaders in the United States are currently contemplating pending federal legislation regarding the establishment of centralized and networked biobanks. Public health practitioners and clinical care providers may be called on to serve pronounced planning roles at the state level. Possible responsibilities include: formulating legislation, gathering public comment, reviewing research proposals, and developing procedures for informed consent, participant withdrawal, and confidentiality protection. State health agencies may also need to create and/or administer banking facilities. Proper planning may ensure that individual rights are protected while research benefits are maximized.     

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.     

Publics and biobanks: Pan-European diversity and the challenge of responsible innovation

This article examines public perceptions of biobanks in Europe using a multi-method approach combining quantitative and qualitative data. It is shown that public support for biobanks in Europe is variable and dependent on a range of interconnected factors: people''s engagement with biobanks; concerns about privacy and data security, and trust in the socio-political system, key actors and institutions involved in biobanks. We argue that the biobank community needs to acknowledge the impact of these factors if they are to successfully develop and integrate biobanks at a pan-European level.     

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.     

Self-guided management of exome and whole-genome sequencing results: changing the results return model

Researchers and clinicians face the practical and ethical challenge of if and how to offer for return the wide and varied scope of results available from individual exome sequencing and whole-genome sequencing. We argue that rather than viewing individual exome sequencing and whole-genome sequencing as a test for which results need to be “returned,” that the technology should instead be framed as a dynamic resource of information from which results should be “managed” over the lifetime of an individual. We further suggest that individual exome sequencing and whole-genome sequencing results management is optimized using a self-guided approach that enables individuals to self-select among results offered for return in a convenient, confidential, personalized context that is responsive to their value system. This approach respects autonomy, allows individuals to maximize potential benefits of genomic information (beneficence) and minimize potential harms (nonmaleficence), and also preserves their right to an open future to the extent they desire or think is appropriate. We describe key challenges and advantages of such a self-guided management system and offer guidance on implementation using an information systems approach.Genet Med15 9, 684–690.     

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     

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.     

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.     

An untapped resource: treatment as a tool for revealing the nature of cognitive processes

This paper focuses on the role of treatment in cognitive neuropsychological research, arguing that treatment for cognitive impairments should be viewed as a powerful methodology for developing, evaluating, and extending cognitive theories. We suggest that the key aim of cognitive neuropsychology should be characterized as the use of data from the investigation and treatment of individuals with cognitive disorders to develop, evaluate, and extend theories of normal cognition. To support this assertion, this paper discusses examples of how treatment studies have informed theory. The major methodological tool is generalization logic, both generalization across items and generalization across tasks. However, an alternative is to use case series methodology to test predicted correlations between particular cognitive skills and response to treatment. These methods enable explicit testing of a theory or discrimination between theories, focusing on the nature of cognitive representations, the architecture of the cognitive system, and the acquisition of cognitive skills.