Basic principles of biobanking: from biological samples to precision medicine for patients.

The term "biobanking" is often misapplied to any collection of human biological materials (biospecimens) regardless of requirements related to ethical and legal issues or the standardization of different processes involved in tissue collection. A proper definition of biobanks is large collections of biospecimens linked to relevant personal and health information (health records, family history, lifestyle, genetic information) that are held predominantly for use in health and medical research. In addition, the International Organization for Standardization, in illustrating the requirements for biobanking (ISO 20387:2018), stresses the concept of biobanks being legal entities driving the process of acquisition and storage together with some or all of the activities related to collection, preparation, preservation, testing, analysing and distributing defined biological material as well as related information and data. In this review article, we aim to discuss the basic principles of biobanking, spanning from definitions to classification systems, standardization processes and documents, sustainability and ethical and legal requirements. We also deal with emerging specimens that are currently being generated and shaping the so-called next-generation biobanking, and we provide pragmatic examples of cancer-associated biobanking by discussing the process behind the construction of a biobank and the infrastructures supporting the implementation of biobanking in scientific research.

Pediatric biobanks and parents of disabled children associations opinions on establishing children repositories in developing countries.

Pediatric biobanks are an indispensable resource for the research needed to bring advances in personalized medicine into pediatric medical care. It is unclear how or when these advances in medical care may reach children, but it is unlikely that research in adults will be adequate. We conducted the screening for a hypothetic problem in various European and American pediatric biobanks based on online surveys through e-mail distribution based on the Biobank Economic Modeling Tool (BEMT) questionnaire model. Participants in the survey had work experience in biobanking for at least 3 years or more. Contact information about the survey participants was confirmed on the social networks profiles (LinkedIn), as well as on generally available websites. First, we tried creating a model which can show the pediatric preclinical and basic clinical phase relationship and demonstrate how pediatric biobanking is linked to this process. Furthermore, we tried to look for new trends, and the final goal is to put the acquired knowledge into practice, so medical experts and patients could gain usable benefit from it. We concluded that leading positions must take into account ethical and legal aspects when considering the decision to include children in the biobank collection. However, communication with parents and children is essential. The biobank characteristics influence the biobank's motives to include children in the consent procedure. Moreover, the motives to include children influence how the children are involved in the consent procedure and the extent to which children are able to make voluntary decisions as part of the consent procedure.

[Ethical, legal and social issues publications on biobanks 2011-2018. A scoping review.] / Publicaciones sobre los aspectos éticos, legales y sociales de los biobancos entre 2011-2018. Una revisión panorámica.

BACKGROUND: Human-based biobanks have been presented as intermediary agents between donors/participants, the scientific community, the healthcare system, and patients. The objective of this systematic review was to contribute with an updated thematic synthesis in Spanish of the international literature (2011-2018) regarding ethical, legal, and social issues on contemporary biobanks. METHODS: A scoping review and thematic analysis were carried out on biobanks' ethical, legal, and social issues. The following databases were searched: Web of Science, SciELO, and Dialnet. The review included 2011-2018 publications with the term "biobank" or "biobanco" in English, Spanish, Portuguese, and French. RESULTS: A total of 153 publications were analyzed. The most published themes were: informed consent, biobanks as a scientific tool, other ethical issues, public engagement, and regulation. While documents published in English provide studies with a broader anthropologic approach and display the participatory turn, in Spanish a technical approach is more common. Aportar datos y cifras principales. CONCLUSIONS: Publications confirm and support biobanks' relevance in current and future biomedical research, but also illustrate the entanglement of a diverse range of healthcare institutions and relations. Biobanks' techno-scientific issues cannot be split from the ethical, legal, and social ones or place them as secondary; all of them are co-produced. This review points to current topics and challenges which need to be addressed to establish transparent, accountable, dynamic, and trust-worthy biobanks.

OBJETIVO: Los biobancos, con muestras de origen humano, han sido definidos como agentes intermedios entre los donantes/participantes, la comunidad científica, el sistema sanitario y los pacientes. El objetivo de esta revisión fue aportar una revisión de la literatura internacional actualizada (2011-2018), que incluyera publicaciones en español y sintetizara los temas más publicados sobre los aspectos éticos, legales y sociales de los biobancos. METODOS: Se llevó a cabo una revisión panorámica y un análisis temático de las publicaciones que abordaban los aspectos éticos, legales y sociales de los biobancos. Se realizaron búsquedas en las bases de datos Web of Science, SciELO y Dialnet. Se incorporaron publicaciones entre 2011-2018 con el término "biobank" o "biobanco" en inglés, español, portugués y francés. RESULTADOS: Se incluyeron 153 publicaciones. Los temas con más publicaciones fueron: consentimiento informado, el biobanco como herramienta científica, otras cuestiones éticas, participación ciudadana y regulación. Se encontró una clara diferencia entre las publicaciones en inglés y español. Las primeras se centraron en el giro participativo, mientras que las segundas se situaron más en una esfera técnica. CONCLUSIONES: Las publicaciones señalan la relevancia de los biobancos en la investigación biomédica contemporánea y futura, así como el entramado de instituciones y relaciones que los componen. Las cuestiones científico-técnicas de los biobancos no pueden separarse de las éticas, legales y sociales, ni relegarlas a un segundo plano, ya que se coproducen. La revisión sintetizó los temas y retos existentes para establecer unos biobancos transparentes, responsables, dinámicos y que fomenten la confianza ciudadana.

Future-proofing biobanks' governance.

Good biobank governance implies-at a minimum-transparency and accountability and the implementation of oversight mechanisms. While the biobanking community is in general committed to such principles, little is known about precisely which governance strategies biobanks adopt to meet those objectives. We conducted an exploratory analysis of governance mechanisms adopted by research biobanks, including genetic biobanks, located in Europe and Canada. We reviewed information available on the websites of 69 biobanks, and directly contacted them for additional information. Our study identified six types of commonly adopted governance strategies: communication, compliance, expert advice, external review, internal procedures, and partnerships. Each strategy is implemented through different mechanisms including, independent ethics assessment, informed consent processes, quality management, data access control, legal compliance, standard operating procedures and external certification. Such mechanisms rely on a wide range of bodies, committees and actors from both within and outside the biobanks themselves. We found that most biobanks aim to be transparent about their governance mechanisms, but could do more to provide more complete and detailed information about them. In particular, the retrievable information, while showing efforts to ensure biobanks operate in a legitimate way, does not specify in sufficient detail how governance mechanisms support accountability, nor how they ensure oversight of research operations. This state of affairs can potentially undermine biobanks' trustworthiness to stakeholders and the public in a long-term perspective. Given the ever-increasing reliance of biomedical research on large biological repositories and their associated databases, we recommend that biobanks increase their efforts to future-proof their governance.

Biospecimens, Research Consent, and Distinguishing Cell Line Research.

Newly revised regulations for human research affecting translational oncology will become effective in January 2019. A substantial component of the debate leading to this revision was how to regulate biospecimen research; specifically, whether all biospecimens should be considered inherently "identifiable," thereby necessitating informed consent for use in research. The famous cases seminal to this discussion involve cancer cell lines, but the unique features of this kind of biospecimen research were largely missing from the regulatory deliberation. However, special aspects of cell line research-at the stages of procurement, generation, evolution, and sharing-alter how society should balance participant interests against the goals of research. Recommendations are offered to cancer researchers and policymakers going forward to enable ethically appropriate regulation of biospecimen research across its diverse spectrum.

Authorization of tissues from deceased patients for genetic research.

Tissues from deceased donors provide important data for genomic research and Organ Procurement Organizations (OPOs) play a significant role. To understand the decisions of families who donated for transplantation and made decisions about donation to the Genotype-Tissue Expression Project (GTEx), we examined donation decisions of family decision makers (FDMs). 413 families were interviewed by telephone. The OPO staff who made the transplant and research requests completed self-administered surveys; a total of 309 matching surveys from 99 OPO staff were obtained. 76.8% of families donated to the GTEx project. Logistic regression analysis found that FDM consent to GTEx donation was associated with endorsement of policies to promote biobanking (OR = 1.35), positive attitudes about medical research (OR = 1.1), lack of concern regarding a breach of confidentiality (OR = 1.54), comfort with tissue donation (OR = 1.24), and prior authorization to solid organ donation (OR = 3.17). OPO staff characteristics associated with GTEx donation included being female (OR = 3.57), White (OR = 4.97), comfort with hospital staff role in donation (OR = 1.61), and number of topics discussed with families (OR = 57.9). Donor type, FDM attitudes, OPO staff sociodemographics, OPO comfort with the GTEx authorization process, and intensity of discussing research-specific issues were significantly associated with GTEx donation decisions.

The European General Data Protection Regulation: challenges and considerations for iPSC researchers and biobanks.

Increasingly, human induced pluripotent stem cells (iPSC) and their associated genetic and clinical information are being used in a wide range of applications, with large biobanks being established to support and increase their scientific use. The new European General Data Protection Regulations, which comes into effect in 2018, will have implications for biobanks that generate, store and allow research access to iPSC. This paper describes some of the challenges that iPSC biobanks face and suggests some points for the development of appropriate governance structures to address these new requirements. These suggestions also have implications for iPSC research in general.

Genes, cells, and biobanks: Yes, there's still a consent problem.

From a research perspective, the interest in biobanking continues to intensify. Governments and industry have invested heavily in biobanks, as exemplified by initiatives like the United Kingdom Biobank and United States' Precision Medicine Initiative. But despite this enthusiasm, many profound legal and ethical challenges remain unresolved. Indeed, there continues to be disagreements about how best to obtain consent and the degree and nature of control that research participants retain over donated samples and health information. Emerging social trends-including concerns about commercialization and perceived rights of continuing control ("biorights")-seem likely to intensify these issues.

Establishing an academic biobank in a resource-challenged environment.

Past practices of informal sample collections and spreadsheets for data and sample management fall short of best-practice models for biobanking, and are neither cost effective nor efficient to adequately serve the needs of large research studies. The biobank of the Sydney Brenner Institute for Molecular Bioscience serves as a bioresource for institutional, national and international research collaborations. It provides high-quality human biospecimens from African populations, secure data and sample curation and storage, as well as monitored sample handling and management processes, to promote both non-communicable and infectious-disease research. Best-practice guidelines have been adapted to align with a low-resource setting and have been instrumental in the development of a quality-management system, including standard operating procedures and a quality-control regimen. Here, we provide a summary of 10 important considerations for initiating and establishing an academic research biobank in a low-resource setting. These include addressing ethical, legal, technical, accreditation and/or certification concerns and financial sustainability.

CTSA Institution Responses to Proposed Common Rule Changes: Did They Get What They Wanted?

In 2015, the U.S. Department of Health and Human Services (HHS) and 15 other federal departments and agencies proposed revisions to the Federal Policy for the Protection of Human Subjects. In this Notice of Proposed Rulemaking (NPRM), the departments sought to strengthen, modernize, and make more effective human subjects regulations while reducing administrative burden, delay, and ambiguity. We reviewed public comments from National Institutes of Health (NIH)-funded Clinical and Translational Science Awards (CTSA) institutions on key provisions of the NPRM to understand how the proposed changed were received at research-intensive institutions. CTSA institutions responding to the proposed rule were predominantly opposed to the major proposals, including proposed changes to the treatment of de-identified biospecimens, demonstrating a lack of support from academic medical centers. In January 2017, a Final Rule was issued. We compare the Final Rule to what was proposed.

Community recommendations on biobank governance: Results from a deliberative community engagement in California.

United States-based biorepositories are on the cusp of substantial change in regulatory oversight at the same time that they are increasingly including samples and data from large populations, e.g. all patients in healthcare system. It is appropriate to engage stakeholders from these populations in new governance arrangements. We sought to describe community recommendations for biorepository governance and oversight using deliberative community engagement (DCE), a qualitative research method designed to elicit lay perspectives on complex technical issues. We asked for stakeholders to provide input on governance of large biorepositories at the University of California (UC), a public university. We defined state residents as stakeholders and recruited residents from two large metropolitan areas, Los Angeles (LA) and San Francisco (SF). In LA, we recruited English and Spanish speakers; in SF the DCE was conducted in English only. We recruited individuals who had completed the 2009 California Health Interview Survey and were willing to be re-contacted for future studies. Using stratified random sampling (by age, education, race/ethnicity), we contacted 162 potential deliberants of whom 53 agreed to participate and 51 completed the 4-day DCE in June (LA) and September-October (SF), 2013. Each DCE included discussion among deliberants facilitated by a trained staff and simultaneously-translated in LA. Deliberants also received a briefing book describing biorepository operations and regulation. During the final day of the DCE, deliberants voted on governance and oversight recommendations using an audience response system. This paper describes 23 recommendations (of 57 total) that address issues including: educating the public, sharing samples broadly, monitoring researcher behavior, using informative consent procedures, and involving community members in a transparent process of biobank governance. This project demonstrates the feasibility of obtaining meaningful input on biorepository governance from diverse lay stakeholders. Such input should be considered as research institutions respond to changes in biorepository regulation.

Regulation of genomic and biobanking research in Africa: a content analysis of ethics guidelines, policies and procedures from 22 African countries.

BACKGROUND: The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when. METHODS: In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. RESULTS: Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. CONCLUSIONS: There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers.

Has the biobank bubble burst? Withstanding the challenges for sustainable biobanking in the digital era.

Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks.

What Potential Donors in Research Biobanking Want to Know: A Large Population Study of the Italian Twin Registry.

Donation of human tissues for research and ELSI (ethical, legal, and social issues) of biobanking are increasingly debated issues. While several studies have highlighted patients' concerns, little is known about opinions and preferences of healthy potential donors. Further investigations in this respect may allow communication procedures tailored to participants' needs. Based on the Italian Twin Registry, a cross-sectional survey was conducted among twins who had not yet donated biological samples for research. The objective was to assess the importance these potential donors attributed to specific procedures and pieces of communication related to research biobanking. A self-administered questionnaire was constructed and validated. Items were as follows: potential agreement on use of biological samples for research; knowledge of biobanks; and importance given to privacy protection and to communication of general and individual tests results, study objectives, type and amount of participant involvement, location and duration of sample storage, and benefits and potential risks. Multivariate analysis was performed to estimate the association of these items with sociodemographic factors as well as with perceived health status and chronic or long-term diseases. The questionnaire was mailed to 4894 twins aged 18-65 (response rate 34%). One-third of subjects already knew about biobanks, 52% had some knowledge, and 20% were uninformed. A majority expressed unconditional agreement to sample use for research. Only 6% of respondents considered privacy protection not important in research biobanking. Knowledge of biobanks predicted attention to most of the issues. Higher education was associated with more frequent concern about type and amount of involvement, but less frequent concern about place and time of storage, and presence of benefits. Women were more attentive to research biobanking. This study supports the need of procedures tailored on different donors' concerns and highlights the social value of population biobanks. Furthermore, the results call for greater efforts in the promotion of research biobanking.

23andMe: a new two-sided data-banking market model.

BACKGROUND: Since 2006, the genetic testing company 23andMe has collected biological samples, self-reported information, and consent documents for biobanking and research from more than 1,000,000 individuals (90% participating in research), through a direct-to-consumer (DTC) online genetic-testing service providing a genetic ancestry report and a genetic health report. However, on November 22, 2013, the Food and Drug Administration (FDA) halted the sale of genetic health testing, on the grounds that 23andMe was not acting in accordance with federal law, by selling tests of undemonstrated reliability as predictive tests for medical risk factors. Consumers could still obtain the genetic ancestry report, but they no longer had access to the genetic health report in the United States (US). However, this did not prevent the company from continuing its health research, with previously obtained and future samples, provided that consent had been obtained from the consumers concerned, or with health reports for individuals from other countries. Furthermore, 23andMe was granted FDA authorization on February 19, 2015, first to provide reports about Bloom syndrome carrier status, and, more recently, to provide consumers with "carrier status" information for 35 genes known (with high levels of confidence) to cause disease. DISCUSSION: In this Debate, we highlight the likelihood that the primary objective of the company was probably two-fold: promoting itself within the market for predictive testing for human genetic diseases and ancestry at a low cost to consumers, and establishing a high-value database/biobank for research (one of the largest biobanks of human deoxyribonucleic acid (DNA) and personal information). By dint of this marketing approach, a two-sided market has been established between the consumer and the research laboratories, involving the establishment of a database/DNA biobank for scientific and financial gain. We describe here the profound ethical issues raised by this setup.

Privacy and Biobanking in China: A Case of Policy in Transition.

Disease-based biobanks have operated in hospitals and research institutes in China for decades, and China has recently embarked on a plan to establish further biobank networks with the aim of promoting data sharing among the existing biobanks. Although the Chinese Constitution has only recently begun to recognize individual privacy as a distinct and independent constitutional right, biobanking in China has been loosely regulated under a patchwork of sometimes overlapping laws (such as the Interim Measures for the Administration of Human Genetic Resources) and regulatory instruments, as well as and the policies of individual biobanks and networks of biobanks (such as the Shanghai Biobank Network Guidelines). A Draft Ordinance on Human Genetics Resources is currently being developed that will deal in more detail than previous laws with issues such as management measures, legal liability, and punishment for violations. International data sharing will be tightly regulated under this new law, and individual biobanks' policies such as the Shanghai Guidelines may choose to regulate such sharing even more. In contrast with national regulatory instruments, the Shanghai Guidelines also contain detailed de-identification policies, and explicitly endorse broad consent.

Constructing populations in biobanking.

This article poses the question of whether biobanking practices and standards are giving rise to the construction of populations from which various biobanking initiatives increasingly draw on for legitimacy? We argue that although recent biobanking policies encourage various forms of engagement with publics to ensure legitimacy, different biobanks conceptualize their engagement strategies very differently. We suggest that biobanks undertake a broad range of different strategies with regard to engagement. We argue that these different approaches to engagement strategies are contributing to the construction of populations, whereby specific nationalities, communities, societies, patient groups and political systems become imbued or bio-objectified with particular characteristics, such as compliant, distant, positive, commercialized or authoritarian. This bio-objectification process is problematic in relation to policy aspirations ascribed to biobanking engagement since it gives rise to reified notions of different populations.

Sharing and Reuse of Sensitive Data and Samples: Supporting Researchers in Identifying Ethical and Legal Requirements.

Availability of and access to data and biosamples are essential in medical and translational research, where their reuse and repurposing by the wider research community can maximize their value and accelerate discovery. However, sharing human-related data or samples is complicated by ethical, legal, and social sensitivities. The specific ethical and legal requirements linked to sensitive data are often unfamiliar to life science researchers who, faced with vast amounts of complex, fragmented, and sometimes even contradictory information, may not feel competent to navigate through it. In this case, the impulse may be not to share the data in order to safeguard against unintentional misuse. Consequently, helping data providers to identify relevant ethical and legal requirements and how they might address them is an essential and frequently neglected step in removing possible hurdles to data and sample sharing in the life sciences. Here, we describe the complex regulatory context and discuss relevant online tools-one which the authors co-developed-targeted at assisting providers of sensitive data or biosamples with ethical and legal questions. The main results are (1) that the different approaches of the tools assume different user needs and prior knowledge of ethical and legal requirements, affecting how a service is designed and its usefulness, (2) that there is much potential for collaboration between tool providers, and (3) that enriched annotations of services (e.g., update status, completeness of information, and disclaimers) would increase their value and facilitate quick assessment by users. Further, there is still work to do with respect to providing researchers using sensitive data or samples with truly 'useful' tools that do not require pre-existing, in-depth knowledge of legal and ethical requirements or time to delve into the details. Ultimately, separate resources, maintained by experts familiar with the respective fields of research, may be needed while-in the longer term-harmonization and increase in ease of use will be very desirable.