HEALTH POLICY/ETHICS
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective Carla Pereira Beak, BSc, MPP,1 Sophie B. Chargé, PhD,2 Rosario Isasi, JD, MPH,1 Bartha M. Knoppers, PhD1 Centre of Genomics and Policy, McGill University, Montreal QC
1
Canadian Blood Services, Ottawa ON
2
Abstract
Résumé
In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS—in collaboration with researchers from the Stem Cell Network—have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.
En 2013, la Société canadienne du sang (SCS) a lancé la Banque publique nationale de sang de cordon ombilical (BPNSCO) : un programme de prélèvement, de traitement, d’analyse et d’entreposage d’unités de sang de cordon ombilical ayant fait l’objet d’un don pour une utilisation dans le cadre de greffes. La mise sur pied d’un programme permettant l’utilisation, aux fins de la recherche biomédicale, du sang de cordon ombilical ne pouvant être mis en banque ni être utilisé pour des greffes constitue une composante clé de la création de la BPNSCO. Conjointement avec l’élaboration de processus et de politiques permettant la gestion de la BPNSCO et du programme de recherche sur le sang de cordon ombilical, la SCS (en collaboration avec les chercheurs du Réseau de cellules souches) ont également conçu des outils pédagogiques permettant l’offre de renseignements pertinents aux populations visées, de façon à faciliter la mise en œuvre et la gestion des activités. Nous décrivons ici l’un de ces outils : le REB Primer on Research and Cord Blood Donation (le « guide »). Ce « guide » souligne les enjeux éthiques et légaux clés, et identifie les documents canadiens pertinents en ce qui concerne l’utilisation de sang de cordon ombilical aux fins de la recherche biomédicale. Ce « guide » présente également la BPNSCO et décrit les systèmes qui sont mis en œuvre par la SCS pour répondre aux questions éthiques. Il a pour but d’aider les conseils d’éthique de la recherche à évaluer l’acceptabilité éthique des protocoles de recherche, de faciliter l’harmonisation des processus décisionnels en offrant un cadre de référence commun et de souligner le rôle des conseils d’éthique de la recherche dans les cadres de gouvernance. Grâce à ce « guide », nous espérons illustrer la façon dont l’élaboration de tels outils pédagogiques peut faciliter la mise en œuvre et la gestion éthiques de programmes associés à la recherche sur les cellules souches au Canada et à l’étranger.
Key Words: Cord blood donation, research, education, ethics, research ethics boards, REBs Competing Interests: None declared. Received on February 25, 2014 Accepted on May 16, 2014
J Obstet Gynaecol Can 2015;37(5):443–450
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INTRODUCTION
C
ord blood stem cells provide a source of blood stem cells (i.e., hematopoietic stem cells) that are an alternative to the more established sources of blood stem cells such as bone marrow and peripheral blood. The first report of hematopoietic reconstitution by transplantation of cord blood was in 1989. It described how a boy with Fanconi’s anemia received cord blood from his baby sister to restore normal blood production.1 By 2010 cord blood had been used in the treatment of over 20 000 patients,2 for over 50 blood-related diseases and disorders.3 In Canada, it is estimated that 70% of patients who need a blood stem cell transplant are unable to find a suitable match in their own family,4 and they rely heavily on international stem cell banks which often do not provide stem cells with the ethnic diversity that is required by Canadian patients. Recognizing the need for a reliable, cost-effective source of HLA-diverse, quality-controlled, and ethically sourced cord blood units for transplantation, Canadian Blood Services developed the National Public Cord Blood Bank, which began operation in 2013.5 Working in collaboration with select hospital collection sites across the country, it is responsible for the collection, processing, testing, and storage of cord blood units for allogenic use in transplantation by patients in Canada and abroad.3 It works within the Canadian Blood Services OneMatch Stem Cell and Marrow Network, which coordinates matching stem cell sources with patients in need.3 Alongside the increased medical use, there has been a growing body of research on cord blood. Some research focuses on improving protocols for collection, manufacturing, and storing samples to optimize the therapeutic use of cord blood cells for transplantation.6 Other research explores the potential use of cord blood cells for the treatment of both hematopoietic and nonhematopoietic diseases.6 Of particular interest is the use of cord blood cells to generate induced pluripotent stem cells.2,7 Like embryonic stem cells, induced pluripotent stem cells are capable of forming any cell lineage in the body. This creates the opportunity for cord blood cells to be used in the treatment of any number of disorders. However, further research is needed to optimize current protocols for blood stem cell transplantation and to investigate the expanded potential of cord blood in the development of novel therapies, including for regenerative medicine. ABBREVIATIONS NPCBB National Public Cord Blood Bank REB
research ethics board
SCN
Stem Cell Network
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The establishment of the NPCBB creates an opportunity to provide cord blood to investigators in this active field of research. Indeed, it is estimated that only 25% to 40% of all cord blood units collected are bankable. The remaining 60% to 75% of units are not bankable for transplantation purposes because of low cell counts.8 These figures show that potentially a large number of units could become available to the biomedical research community. More specifically, within the next six years, the NPCBB anticipates collecting a total of approximately 57 000 cord blood units, which could lead to approximately 30 000 to 40 000 units being available for research.9 RESEARCH USE OF CORD BLOOD IN CANADA
In 2009, a survey of Canadian researchers found a patchwork of sources and standards governing the collection and use of cord blood by the research community.10 In response, members of our group (R.I., B.M.K.) published an article in this journal which identified the growing use of cord blood in biomedical research as an area requiring ethical and legal examination and harmonization in Canada.11 Six recommendations were made; these broadly called for: 1. increased education on the utility and application of cord blood, 2. increased rigour and consistency in obtaining (prospective) informed consent for the research use of cord blood, and 3. increased efforts to make anonymized cord blood available for research and clinical trials. From the donor perspective, a recent survey suggested that patients’ attitudes towards the donation of biological materials for (stem cell) research is positive, and that patients’ concerns could be mitigated with consent, transparency, and trust.12 The creation of the NPCBB provides an opportunity for many of these issues to be addressed. The mission of Canadian Blood Services is to provide a “safe, secure, cost-effective, affordable and accessible” supply of quality blood, blood products, and their alternatives; and, as part of its vision, Canadian Blood Services supports biomedical research to advance transfusion and transplantation medicine.10 Canadian Blood Services is therefore developing mechanisms by which cord blood samples not used therapeutically can be provided to bona fide scientists for biomedical research purposes. However, to maintain public support for cord blood donation for research use, both the sample acquisition process and the research itself must uphold ethical principles and legal requirements. To address this, Canadian Blood Services is implementing a
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
thorough system of governance and has instituted processes that address key ethical issues. In particular, a customdesigned informed consent process has been developed to ensure that cord blood that will be used in biomedical research is ethically obtained from donors. Furthermore, Canadian Blood Services has supported the development of educational tools which help ensure cord blood research programs are implemented and run ethically. The two main educational tools developed for the NPCBB program target two important stakeholders. The Maternal Information Kit was developed for pregnant women and potential donors. It contains several brochures that provide general information on cord blood donation, provide information about Canadian Blood Services privacy policies and procedures, and outline the program put in place to manage cord blood donation for transplantation. Once the research program is operational, the Maternal Information Kit will also include information about donating to biomedical research. The Maternal Information Kit is provided to women during prenatal care, together with the “Permission to Collect” consent form that prospectively allows staff to collect the sample at the time of delivery. This educational tool is central to ensuring consent, is truly informed, and therefore ethical. The second tool is the REB Primer on Research and Cord Blood Donation (hereinafter the Primer), which was developed by our group (Centre of Genomics and Policy, McGill University) for members of research ethics boards. Since biomedical research using cord blood cells entails the use of human biological material obtained from living human participants, REB review and approval of research projects is required in most circumstances before initiation of the research.13 Like any other scientific research involving human samples, systems are required to ensure cord blood samples and all related data are legally and ethically obtained and managed, and any distinct ethical issues are addressed. In Canada, REBs are responsible for ensuring these systems are in place and issues are considered. REBs therefore have an important role to play in ensuring adequate protection for donors, thereby making certain that cord blood collected and used for biomedical research purposes upholds national and international ethical principles and guidelines. Consequently, an educational tool to assist REBs perform this task can be useful in creating an ethical research landscape in Canada. REB PRIMER ON RESEARCH AND CORD BLOOD DONATION
The Primer has as an ultimate purpose to contribute to capacity building of REBs, and it is intended both to assist REBs in evaluating the ethical acceptability of research
protocols and to facilitate harmonized decision-making by providing a common reference. The goals of the Primer are: •• to introduce the National Public Cord Blood Bank and illustrate how the current NPCBB system addresses ethical concerns and legal requirements; •• to highlight some of the more common ethical issues faced by REBs when reviewing protocols for cord blood donation for biomedical research use; and •• to identify Canadian documents that are relevant to the ethical review of cord blood research protocols. We will present below excerpts to illustrate the utility of such educational tools in the implementation of policies and procedures to promote the ethical conduct of research, and to provide an overview of Canadian Blood Services systems and processes that are currently being developed to address ethical concerns. THE NATIONAL PUBLIC CORD BLOOD BANK
A major goal of the Primer is to introduce REB members to the NPCBB and the Canadian Blood Services Cord Blood for Research Program, which aims to increase accessibility to and use of cord blood for biomedical research. In particular, the Primer describes the processes that Canadian Blood Services has developed (but not yet implemented) to date, to obtain consistent and rigorous prospective consent for collection and distribution of cord blood for use in biomedical research. A central component is the “Permission to Collect” consent form (Figure). It is made available to potential donors via the Canadian Blood Services website and via health care professionals affiliated with the NPCBB collection hospitals. The “Permission to Collect” form may be completed at any time during the prenatal period. It is complemented by the Maternal Information Kit, which can be reviewed and discussed at the donor’s convenience. If consent is obtained, then reconfirmed before delivery, cord blood can be collected by hospital or NPCBB staff and distributed to bona fide researchers. To implement this research consent process, the Canadian Blood Services Research Program protocol must be approved by REBs of NPCBB collecting hospitals. Individual research projects will require Canadian Blood Services REB approval, the researcher’s institutional REB approval and a material transfer agreement between the researcher(s) and Canadian Blood Services. The material transfer agreement will contain provisions regarding conditions and requirements for use of the cord blood by the researcher. If the research project is approved, the researcher will be able to submit orders to the Canadian MAY JOGC MAI 2015 l 445
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The signed “Permission to Collect” consent and “Maternal Information Kit” The “Permission to Collect” consent: –– allows staff to collect the cord blood after delivery, and take blood samples from the mother as applicable, which may then be placed in a secure location for future testing and storage • a brochure in the Kit explains the NPCBB and the process of collection and donation for testing, storage and transplantation –– permits staff to access medical records and collect certain personal information about the mother and baby • a brochure in the Kit explains Canadian Blood Services privacy policy –– requests permission to donate samples deemed unsuitable for transplantation to biomedical research (using a “research opt-in” tick box) • a brochure in the Kit explains the process of donation and use for research including a list of common examples of research purposes • Canadian Blood Services website provides lay summaries of approved research projects –– identifies the risks and benefits to participation, highlights that there are no costs or reimbursements, describes the potential uses of the cord blood sample and the process for withdrawal (if desired) • brochures in the Kit provide further detailed information on these subjects Consent forms will be available at http://www.blood.ca/cordblood.
Blood Services Cord Blood for Research Program for the delivery of fresh, de-identified cord blood within 48 hours of collection. These processes are intended to evolve with the maturation of the NPCBB and the need to align with the requirements of all NPCBB collecting hospitals. ETHICAL CONSIDERATIONS
A fundamental goal of the Primer is to highlight the ethical considerations relevant to cord blood donation and use for biomedical research purposes that REBs will need to address. The Primer focuses on core ethical principles such as autonomy (e.g., informed consent, right to withdraw), respect for privacy and confidentiality (e.g., protection of donor identity), and the non-commercialization of the human biological materials (e.g., translated into restrictions on monetary compensation for donation). It also addresses other fundamental ethical principles such as beneficence, justice, and research merit and integrity.13 Furthermore, the Primer deals with governance issues and describes how the current Canadian Blood Services program structures and policies have been established in order to create a coherent ethical and governance framework that encourages respect for donors. 1. Research Consent
A fundamental ethical principle is autonomy or respect for persons, which in the research setting translates into obtaining “free, informed and ongoing” consent.13 Linked to the principle of autonomy that underlies the doctrine of 446 l MAY JOGC MAI 2015
informed consent are issues such as conflicts of interest, full disclosure, and opportunity to withdraw, as discussed below. “Free,” or voluntary, consent requires that donors should not be influenced towards or coerced into participation. Coercion may occur when individuals in a position of authority have reason to affect a donor’s decision to participate, or when incentives are put in place that may affect a donor’s decision. In the context of cord blood donation for biomedical research, care must be taken to ensure that those involved in obtaining consent are not in conflicts of interest or motivated to influence donors. Donors must be aware that there are no direct financial or medical benefits for the mother or child. However, it should also be noted that while there are currently no direct medical benefits derived by donors from cord blood units that are considered unsuitable for banking (e.g., samples with low cell count), this may not remain the case if research using these samples proves fruitful. The therapeutic potential of such samples should therefore be clearly presented to donors as research evolves, since increased personal utility of the sample may influence a donor’s decision to donate to research. For consent to be “informed,” full disclosure of any information that may affect a donor’s decision to participate should be provided. There are many aspects and elements that may be relevant, and the institutions involved must decide what material information should be included for
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
any particular research project. Moreover, information provided should be in plain language that prospective donors can understand. Donors should be given sufficient time to consider this information before a decision is made. They should be informed of possible alternatives to participate, including the right to refuse or discontinue participation. When obtaining consent for cord blood collection and use, the donor must be made aware of the purpose(s), risks, and benefits of the entire process, how samples and personal information are collected and managed in the hospital, and how samples and data are going to be used and managed by the researcher. To obtain a robust and prospective consent for cord blood donation, several key disclosure elements have been identified.14,15 The minimum requirements for consent generally include awareness that donation is voluntary; the donor is aware of their options (discard, donate for research, public banking, private storage); permission is given for sample testing and any required disclosure of results (e.g., tests for communicable/infectious diseases); the donor agrees to provide family history and to be contacted in the future; and the donor is notified of safeguards to protect privacy and confidentiality (including traceability measures). One area of informed consent that has ethical and legal implications for the research use of cord blood in particular is the need to ensure that donors are aware of the commercial potential of their donation, because commercialization may alter their willingness to donate to research.16 Awareness of commercial potential extends beyond the notification that financial benefits will not be realized by the donor (i.e., mother or child), as described above in the context of inducements. Since donors in public banks are primarily giving samples altruistically for the treatment of others, they should be informed that cord blood (and derivate materials) may be used for commercial purposes, and while the donor will not have legal or financial interest in any resulting commercial development or patents, there is the potential for researchers or companies to generate profits from samples used in commercial applications. Lastly, “ongoing” consent implies that the consent process does not end once the consent forms are signed. Researchers have a duty to inform donors of any new information that may influence their decision to participate. Donors must also be aware of the option to withdraw consent. Withdrawal should come without disadvantage or reprisal, and conditions under which samples or data cannot be withdrawn should be clearly outlined. It should be noted that the window of opportunity to withdraw from a
research project after collection of the cord blood sample may be small, particularly if the sample is distributed to researchers fresh (i.e., not frozen). However, one overarching question that needs to be answered in any banking system is this: when should consent be obtained? This has been a controversial issue, as outlined by Broder et al.17 Requiring consent to be obtained during the prenatal period has been used as a mechanism to ensure that consent is truly informed. It gives expectant parents time to consider the information and to ask questions before the onset of labour. While this practice is generally considered ideal, it effectively denies access to women who do not receive prenatal care or who have not been exposed to educational or promotional material regarding public cord blood banking. As a result, it limits ethnic representation and genetic diversity in banked samples. Many banks therefore are changing their policies, and are allowing either a one-time or a phased consent process (separating the consent for collection of the cord blood from the consent for testing, banking, and for research and/or therapeutic uses) to be initiated during hospital admissions in the early stages of labour.18 2. Privacy
Privacy refers to “an individual’s right to be free from intrusion or interference” with respect to their “bodies, personal information, expressed thoughts and opinions, personal communications with others, and spaces they occupy.”13 It calls for individual and institutional requirements for confidentiality (the duty to safeguard information) and security (measures to protect information).13 In the context of cord blood donation and research, privacy applies to the donation itself and the management of subsequent information and data from the mother and her baby. Institutions collecting and managing cord blood need to ensure their staff and collaborators are familiar with their privacy and confidentiality obligations. Decisions must also be made regarding the donor information that will be required and used in biomedical research and how to safeguard donor information securely. One key research issue is that of sample traceability. As described by Sugarman et al.,19 samples to be used in transplantation generally remain linked to information about the donor. Linkage of samples to donor information allows samples to be identified if at a future date the donor was found to have a genetic or infectious disease that could be transmissible through the sample. However, this linkage also comes with risks to privacy of the donor. While safety implications may outweigh the privacy concerns in the context of cord blood banking for transplantation, this is not necessarily the case for biomedical research use. MAY JOGC MAI 2015 l 447
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To protect donor privacy, coding or de-identification of samples is generally recommended in research applications, in particular where samples and information may be used in studies whose details have not been specified or may be shared internationally. 3. Governance
The essence of governance is its focus on mechanisms that foster, among other important issues, accountability, transparency, legitimacy, stewardship, and public trust. Governance is generally conceived as the efficient management of organizations and activities. It requires that stem cell banks implement “structures, processes and bodies” that are “independent, accountable, and transparent” in order to ensure “scientific and ethical integrity.”20 In application, it works “at two levels: at the internal level through mechanisms governing the day-today activities of the bank, and at the external level, by independently assessing the overall bank performance and making the bank accountable to all its stakeholders.”20 In research using cord blood, it is important that each of the relevant stakeholders involved in collection, processing, storage, and clinical and biomedical research are represented in governing processes and structures. REBs play an integral part in the governance of research activities by ensuring governance mechanisms are in place and systems are transparent. In order to fulfill this role effectively, REBs and other governance bodies which fulfil review and oversight duties must be separate from and independent of bodies responsible for management and funding of the bank and research programs.20 This type of stewardship is required for research activities to maintain their integrity and sustain public support. Furthermore, to ensure that public benefit is realized from publicly supported research endeavours, the publication of research results and registration of clinical trials is recommended or required by funding agencies13 and professional organizations.21 CANADIAN NORMATIVE DOCUMENTS
The last goal of the Primer is to identify the government agencies and professional organizations that provide normative and ethical guidance on cord blood donation and use in Canada (Table). As stated in the Primer: “REBs should be aware of the norms presented in these documents, how they apply to research, and when necessary use them as resources to aid in decision making.” A number of the documents developed by these agencies and organizations directly address and make recommendations specific to ethical considerations related to cord blood collection and use. 448 l MAY JOGC MAI 2015
A key government text is the Tri-Council Agencies’ TCPS2,13 a foundational document guiding REB review of research projects. It outlines mandatory requirements and provides guidance for the ethical conduct of research, covering many areas relevant to the use of cord blood (e.g., ethics review, consent, privacy and confidentiality). It also contains provisions specific to the use of materials related to human reproduction, which includes cord blood. Also familiar to many REBs is the Canadian Institutes of Health Research publication “Updated Guidelines for Human Pluripotent Stem Cell Research,”22 which offers specific guidelines for the use of cord blood in the derivation of pluripotent stem cells. It outlines unique consent and research requirements, such as (in some cases) Stem Cell Oversight Committee review and the consent of both parents (if relevant). Documents from professional organizations should also play a role in ethical deliberation by REBs. The Society of Obstetricians and Gynaecologists of Canada’s Clinical Practice Guideline “Umbilical Cord Blood Banking: Implications for Perinatal Care Providers,”23 and various policies24 and research projects10 funded by the Stem Cell Network address the ethical collection and use of cord blood. These documents address issues such as donor recruitment, timing and scope of consent, disclosure of test results, and publication of research results. Both also highlight the importance of public (versus for-profit) cord blood banks in therapeutic and research use of cord blood. In its conclusion, the Primer acknowledges that further work must be done to address various remaining questions and to ensure that REBs are harmonized in their decisionmaking. Areas that may require further research and analysis include •• consideration of whether a centralized ethics review system would more efficiently and consistently review research projects utilizing samples from a national cord blood bank; •• exploration of the experiences of women in Canada who have donated cord blood and how the system can be optimized to meet their needs and preferences; •• examination of the role and requirements for paternal consent, and particularly how to reconcile the CIHR requirement that permission must be obtained from both parents for pluripotent stem cell research using cord blood with international guidelines which only require consent from mothers for cord blood banking; •• review of the legal conceptualization of “ownership” or “custodianship” of cord blood in Canada, and what impact this has on the rights, obligations, and liabilities of the children, parents, banks, and researchers; and
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
Key Canadian organizations and their documents Organization
Documents
Health Canada (HC) HC is tasked with ensuring medical products available in Canada meet appropriate quality and safety standards.
Food and Drug Act (FDA): Enabling legislation. Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations): outlines the responsibilities that establishments that distribute or import cells and tissues for transplantation must follow to ensure product safety. Food and Drug Regulations (FDR): outlines the requirements for drug products to obtain authorization for sale and use in Canada.
Public Health Agency of Canada (PHAC) PHAC is responsible for public health at the national level, including protecting Canadians from infectious diseases.
Human Pathogens and Toxins Act (HPTA): establishes a safety system to protect the public from risks posed by substances that may contain a pathogen, such as blood products. Canadian Biosafety Standards and Guidelines (CBSG): outlines the requirements for research facilities where infectious material or toxins for non-medical use are handled or stored, and provides guidance on how those requirements are to be achieved.
The Tri-Council Agencies Canada’s three research funding agencies—the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council, and the Social Sciences and Humanities Research Council
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS2): guidelines for ethical conduct in research involving humans, required standards for organizations who receive funding from any of the three agencies.
Canadian Institutes of Health Research (CIHR) CIHR is the primary funding agency for health research in Canada, and monitors research involving human pluripotent stem cells.
Guidelines for Human Pluripotent Stem Cell Research (the Guidelines): guidelines for research involving stem cells generated from human embryos, as well as the study of pluripotent stem cell lines from other sources, including umbilical cords and placentas.
Society of Obstetricians and Gynaecologists of Canada (SOGC) SOGC is composed of health professionals who form a leading authority on reproductive health care.
Clinical Practice Guidelines: guidelines for prenatal care providers regarding the counselling, procedural, and ethical implications of cord blood banking.
Stem Cell Network (SCN) SCN, by facilitating collaborations, acts as a “catalyst for Canadian research that translates stem cell research into new therapies, commercial products and public policy.”25
SCN has developed a Public Policy & Ethical, Legal and Social Issues research program, generated policy papers, and funded academic research on a range of topics including the use of cord blood for research.
•• discussion of the role of hybrid and private cord blood banks, particularly with respect to the conditions for samples collected from such banks to be ethically transferred and used by bona fide researchers. CONCLUSION
In addition to developing a framework to provide the biomedical research community with a large, consistent source of ethically derived cord blood cells for research that may lead to potential clinical and commercial applications, Canadian Blood Services has supported the development of educational tools to ensure that the systems created are effectively and ethically implemented and managed. These tools were designed to provide information to expectant parents and REBs in particular, but can serve as educational material for broader groups. For this reason, the Primer was written to be accessible to the general public and may serve a broader purpose to increase public awareness of cord blood banking and the policies and procedures public systems are putting in place to protect donors. As the NPCBB matures, its role in facilitating cord blood research and the research
processes described above may also evolve. The Primer can be easily updated and downloaded from the Internet, and will serve as a tool to keep the general public aware of these changes. In addition, the Primer highlights the ethical and legal issues germane to the research use of cord blood samples globally: informed consent, privacy, and governance. Although developed for the Canadian context, the Primer can serve as a model for other countries to achieve similar goals. Through it, we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research. ACKNOWLEDGEMENTS
The authors would like to thank the members of the Canadian Blood Services Cord Blood for Research project team for their input. This project was supported by a grant from Canadian Blood Services and the Stem Cell Network of Canada. The views expressed here are solely those of the authors and do not necessarily represent the views of Canadian Blood Services or the Stem Cell Network. MAY JOGC MAI 2015 l 449
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conduct for research involving humans; December 2010. Available at: http://www.pre.ethics.gc.ca/pdf/eng/tcps2/TCPS_2_FINAL_Web.pdf. Accessed August 7, 2014. 14. Kharaboyan L, Knoppers BM, Avard D, Nisker J. Understanding umbilical cord blood banking: what women need to know before deciding. Womens Health Issues 2007 Sep-Oct;17(5):277–80. 15. Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest 2005;115:2592–7. 16. Petrini C. Ethical and legal considerations regarding the ownership and commercial use of human biological materials and their derivatives. J Blood Med 2012;3:87–96. 17. Broder SM, Ponsaran RS, Goldenberg AJ. US public cord blood banking practices: recruitment, donation, and the timing of consent. Transfusion 2013;53:679–87. 18. Vawter DE, Rogers-Chrysler G, Clay M, Pittelko L, Therkelsen D, Kim D, et al. A phased consent policy for cord blood donation. Transfusion 2002;42:1268–74. 19. Sugarman J, Kaalund V, Kodish E, Marshall MF, Reisner EG, Wilfond BS, et al. Ethical issues in umbilical cord blood banking. Working Group on Ethical Issues in Umbilical Cord Blood Banking. JAMA 1997;278:938–43. 20. Isasi RM, Knoppers BM. Governing stem cell banks and registries: emerging issues. Stem cell research 2009;3:96–105. 21. World Medical Association (WMA): WMA Declaration of Helsinki— ethical principles for medical research involving human subjects. Ferney-Voltaire (FR): WMA; 2013. 22. Canadian Institutes of Health Research. Updated guidelines for human pluripotent stem cell research. Ottawa (ON): CIHR; 2010. Modified February 26, 2013. Available at: http://www.cihr-irsc.gc.ca/e/42071.html. Accessed February 18, 2014. 23. Armson AB; SOGC Maternal Fetal Medicine Committee. Umbilical cord blood banking: implications for perinatal care providers. SOGC Clinical Practice Guideline no. 156, March 2005. J Obstet Gynaecol Can 2005;27(3):263–73. Available at: http://sogc.org/guidelines/ umbilical-cord-blood-banking-implications-for-perinatal-care-providers/. Disclaimer (November 18, 2013): guideline currently being reviewed and updated.
12. Dasgupta I, Bollinger J, Mathews DJH, Neumann NM, Rattani A, Sugarman J. Patients’ attitudes toward the donation of biological materials for the derivation of induced pluripotent stem cells. Cell Stem Cell 2014;14(1):9–12.
24. Stem Cell Network of Canada Policy Development Committee. Stem Cell Network policy on umbilical cord blood collection. Stem Cell Network; 2007. Available at: http://www.stemcellnetwork.ca/uploads/ document-library/policy-papers/UCB_BankingPolicyStatement_ Dec2007.pdf. Accessed August 7, 2014.
13. Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada. Tri-Council policy statement: ethical
25. Stem Cell Network. About us. Stem Cell Network; 2014. Available at: http://www.stemcellnetwork.ca/index.php?page=about-us&hl=eng. Accessed February 18, 2014.
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Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective Carla Pereira Beak, BSc, MPP,1 Sophie B. Chargé, PhD,2 Rosario Isasi, JD, MPH,1 Bartha M. Knoppers, PhD1 Centre of Genomics and Policy, McGill University, Montreal QC
1
Canadian Blood Services, Ottawa ON
2
Abstract
Résumé
In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS—in collaboration with researchers from the Stem Cell Network—have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.
En 2013, la Société canadienne du sang (SCS) a lancé la Banque publique nationale de sang de cordon ombilical (BPNSCO) : un programme de prélèvement, de traitement, d’analyse et d’entreposage d’unités de sang de cordon ombilical ayant fait l’objet d’un don pour une utilisation dans le cadre de greffes. La mise sur pied d’un programme permettant l’utilisation, aux fins de la recherche biomédicale, du sang de cordon ombilical ne pouvant être mis en banque ni être utilisé pour des greffes constitue une composante clé de la création de la BPNSCO. Conjointement avec l’élaboration de processus et de politiques permettant la gestion de la BPNSCO et du programme de recherche sur le sang de cordon ombilical, la SCS (en collaboration avec les chercheurs du Réseau de cellules souches) ont également conçu des outils pédagogiques permettant l’offre de renseignements pertinents aux populations visées, de façon à faciliter la mise en œuvre et la gestion des activités. Nous décrivons ici l’un de ces outils : le REB Primer on Research and Cord Blood Donation (le « guide »). Ce « guide » souligne les enjeux éthiques et légaux clés, et identifie les documents canadiens pertinents en ce qui concerne l’utilisation de sang de cordon ombilical aux fins de la recherche biomédicale. Ce « guide » présente également la BPNSCO et décrit les systèmes qui sont mis en œuvre par la SCS pour répondre aux questions éthiques. Il a pour but d’aider les conseils d’éthique de la recherche à évaluer l’acceptabilité éthique des protocoles de recherche, de faciliter l’harmonisation des processus décisionnels en offrant un cadre de référence commun et de souligner le rôle des conseils d’éthique de la recherche dans les cadres de gouvernance. Grâce à ce « guide », nous espérons illustrer la façon dont l’élaboration de tels outils pédagogiques peut faciliter la mise en œuvre et la gestion éthiques de programmes associés à la recherche sur les cellules souches au Canada et à l’étranger.
Key Words: Cord blood donation, research, education, ethics, research ethics boards, REBs Competing Interests: None declared. Received on February 25, 2014 Accepted on May 16, 2014
J Obstet Gynaecol Can 2015;37(5):443–450
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INTRODUCTION
C
ord blood stem cells provide a source of blood stem cells (i.e., hematopoietic stem cells) that are an alternative to the more established sources of blood stem cells such as bone marrow and peripheral blood. The first report of hematopoietic reconstitution by transplantation of cord blood was in 1989. It described how a boy with Fanconi’s anemia received cord blood from his baby sister to restore normal blood production.1 By 2010 cord blood had been used in the treatment of over 20 000 patients,2 for over 50 blood-related diseases and disorders.3 In Canada, it is estimated that 70% of patients who need a blood stem cell transplant are unable to find a suitable match in their own family,4 and they rely heavily on international stem cell banks which often do not provide stem cells with the ethnic diversity that is required by Canadian patients. Recognizing the need for a reliable, cost-effective source of HLA-diverse, quality-controlled, and ethically sourced cord blood units for transplantation, Canadian Blood Services developed the National Public Cord Blood Bank, which began operation in 2013.5 Working in collaboration with select hospital collection sites across the country, it is responsible for the collection, processing, testing, and storage of cord blood units for allogenic use in transplantation by patients in Canada and abroad.3 It works within the Canadian Blood Services OneMatch Stem Cell and Marrow Network, which coordinates matching stem cell sources with patients in need.3 Alongside the increased medical use, there has been a growing body of research on cord blood. Some research focuses on improving protocols for collection, manufacturing, and storing samples to optimize the therapeutic use of cord blood cells for transplantation.6 Other research explores the potential use of cord blood cells for the treatment of both hematopoietic and nonhematopoietic diseases.6 Of particular interest is the use of cord blood cells to generate induced pluripotent stem cells.2,7 Like embryonic stem cells, induced pluripotent stem cells are capable of forming any cell lineage in the body. This creates the opportunity for cord blood cells to be used in the treatment of any number of disorders. However, further research is needed to optimize current protocols for blood stem cell transplantation and to investigate the expanded potential of cord blood in the development of novel therapies, including for regenerative medicine. ABBREVIATIONS NPCBB National Public Cord Blood Bank REB
research ethics board
SCN
Stem Cell Network
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The establishment of the NPCBB creates an opportunity to provide cord blood to investigators in this active field of research. Indeed, it is estimated that only 25% to 40% of all cord blood units collected are bankable. The remaining 60% to 75% of units are not bankable for transplantation purposes because of low cell counts.8 These figures show that potentially a large number of units could become available to the biomedical research community. More specifically, within the next six years, the NPCBB anticipates collecting a total of approximately 57 000 cord blood units, which could lead to approximately 30 000 to 40 000 units being available for research.9 RESEARCH USE OF CORD BLOOD IN CANADA
In 2009, a survey of Canadian researchers found a patchwork of sources and standards governing the collection and use of cord blood by the research community.10 In response, members of our group (R.I., B.M.K.) published an article in this journal which identified the growing use of cord blood in biomedical research as an area requiring ethical and legal examination and harmonization in Canada.11 Six recommendations were made; these broadly called for: 1. increased education on the utility and application of cord blood, 2. increased rigour and consistency in obtaining (prospective) informed consent for the research use of cord blood, and 3. increased efforts to make anonymized cord blood available for research and clinical trials. From the donor perspective, a recent survey suggested that patients’ attitudes towards the donation of biological materials for (stem cell) research is positive, and that patients’ concerns could be mitigated with consent, transparency, and trust.12 The creation of the NPCBB provides an opportunity for many of these issues to be addressed. The mission of Canadian Blood Services is to provide a “safe, secure, cost-effective, affordable and accessible” supply of quality blood, blood products, and their alternatives; and, as part of its vision, Canadian Blood Services supports biomedical research to advance transfusion and transplantation medicine.10 Canadian Blood Services is therefore developing mechanisms by which cord blood samples not used therapeutically can be provided to bona fide scientists for biomedical research purposes. However, to maintain public support for cord blood donation for research use, both the sample acquisition process and the research itself must uphold ethical principles and legal requirements. To address this, Canadian Blood Services is implementing a
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
thorough system of governance and has instituted processes that address key ethical issues. In particular, a customdesigned informed consent process has been developed to ensure that cord blood that will be used in biomedical research is ethically obtained from donors. Furthermore, Canadian Blood Services has supported the development of educational tools which help ensure cord blood research programs are implemented and run ethically. The two main educational tools developed for the NPCBB program target two important stakeholders. The Maternal Information Kit was developed for pregnant women and potential donors. It contains several brochures that provide general information on cord blood donation, provide information about Canadian Blood Services privacy policies and procedures, and outline the program put in place to manage cord blood donation for transplantation. Once the research program is operational, the Maternal Information Kit will also include information about donating to biomedical research. The Maternal Information Kit is provided to women during prenatal care, together with the “Permission to Collect” consent form that prospectively allows staff to collect the sample at the time of delivery. This educational tool is central to ensuring consent, is truly informed, and therefore ethical. The second tool is the REB Primer on Research and Cord Blood Donation (hereinafter the Primer), which was developed by our group (Centre of Genomics and Policy, McGill University) for members of research ethics boards. Since biomedical research using cord blood cells entails the use of human biological material obtained from living human participants, REB review and approval of research projects is required in most circumstances before initiation of the research.13 Like any other scientific research involving human samples, systems are required to ensure cord blood samples and all related data are legally and ethically obtained and managed, and any distinct ethical issues are addressed. In Canada, REBs are responsible for ensuring these systems are in place and issues are considered. REBs therefore have an important role to play in ensuring adequate protection for donors, thereby making certain that cord blood collected and used for biomedical research purposes upholds national and international ethical principles and guidelines. Consequently, an educational tool to assist REBs perform this task can be useful in creating an ethical research landscape in Canada. REB PRIMER ON RESEARCH AND CORD BLOOD DONATION
The Primer has as an ultimate purpose to contribute to capacity building of REBs, and it is intended both to assist REBs in evaluating the ethical acceptability of research
protocols and to facilitate harmonized decision-making by providing a common reference. The goals of the Primer are: •• to introduce the National Public Cord Blood Bank and illustrate how the current NPCBB system addresses ethical concerns and legal requirements; •• to highlight some of the more common ethical issues faced by REBs when reviewing protocols for cord blood donation for biomedical research use; and •• to identify Canadian documents that are relevant to the ethical review of cord blood research protocols. We will present below excerpts to illustrate the utility of such educational tools in the implementation of policies and procedures to promote the ethical conduct of research, and to provide an overview of Canadian Blood Services systems and processes that are currently being developed to address ethical concerns. THE NATIONAL PUBLIC CORD BLOOD BANK
A major goal of the Primer is to introduce REB members to the NPCBB and the Canadian Blood Services Cord Blood for Research Program, which aims to increase accessibility to and use of cord blood for biomedical research. In particular, the Primer describes the processes that Canadian Blood Services has developed (but not yet implemented) to date, to obtain consistent and rigorous prospective consent for collection and distribution of cord blood for use in biomedical research. A central component is the “Permission to Collect” consent form (Figure). It is made available to potential donors via the Canadian Blood Services website and via health care professionals affiliated with the NPCBB collection hospitals. The “Permission to Collect” form may be completed at any time during the prenatal period. It is complemented by the Maternal Information Kit, which can be reviewed and discussed at the donor’s convenience. If consent is obtained, then reconfirmed before delivery, cord blood can be collected by hospital or NPCBB staff and distributed to bona fide researchers. To implement this research consent process, the Canadian Blood Services Research Program protocol must be approved by REBs of NPCBB collecting hospitals. Individual research projects will require Canadian Blood Services REB approval, the researcher’s institutional REB approval and a material transfer agreement between the researcher(s) and Canadian Blood Services. The material transfer agreement will contain provisions regarding conditions and requirements for use of the cord blood by the researcher. If the research project is approved, the researcher will be able to submit orders to the Canadian MAY JOGC MAI 2015 l 445
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The signed “Permission to Collect” consent and “Maternal Information Kit” The “Permission to Collect” consent: –– allows staff to collect the cord blood after delivery, and take blood samples from the mother as applicable, which may then be placed in a secure location for future testing and storage • a brochure in the Kit explains the NPCBB and the process of collection and donation for testing, storage and transplantation –– permits staff to access medical records and collect certain personal information about the mother and baby • a brochure in the Kit explains Canadian Blood Services privacy policy –– requests permission to donate samples deemed unsuitable for transplantation to biomedical research (using a “research opt-in” tick box) • a brochure in the Kit explains the process of donation and use for research including a list of common examples of research purposes • Canadian Blood Services website provides lay summaries of approved research projects –– identifies the risks and benefits to participation, highlights that there are no costs or reimbursements, describes the potential uses of the cord blood sample and the process for withdrawal (if desired) • brochures in the Kit provide further detailed information on these subjects Consent forms will be available at http://www.blood.ca/cordblood.
Blood Services Cord Blood for Research Program for the delivery of fresh, de-identified cord blood within 48 hours of collection. These processes are intended to evolve with the maturation of the NPCBB and the need to align with the requirements of all NPCBB collecting hospitals. ETHICAL CONSIDERATIONS
A fundamental goal of the Primer is to highlight the ethical considerations relevant to cord blood donation and use for biomedical research purposes that REBs will need to address. The Primer focuses on core ethical principles such as autonomy (e.g., informed consent, right to withdraw), respect for privacy and confidentiality (e.g., protection of donor identity), and the non-commercialization of the human biological materials (e.g., translated into restrictions on monetary compensation for donation). It also addresses other fundamental ethical principles such as beneficence, justice, and research merit and integrity.13 Furthermore, the Primer deals with governance issues and describes how the current Canadian Blood Services program structures and policies have been established in order to create a coherent ethical and governance framework that encourages respect for donors. 1. Research Consent
A fundamental ethical principle is autonomy or respect for persons, which in the research setting translates into obtaining “free, informed and ongoing” consent.13 Linked to the principle of autonomy that underlies the doctrine of 446 l MAY JOGC MAI 2015
informed consent are issues such as conflicts of interest, full disclosure, and opportunity to withdraw, as discussed below. “Free,” or voluntary, consent requires that donors should not be influenced towards or coerced into participation. Coercion may occur when individuals in a position of authority have reason to affect a donor’s decision to participate, or when incentives are put in place that may affect a donor’s decision. In the context of cord blood donation for biomedical research, care must be taken to ensure that those involved in obtaining consent are not in conflicts of interest or motivated to influence donors. Donors must be aware that there are no direct financial or medical benefits for the mother or child. However, it should also be noted that while there are currently no direct medical benefits derived by donors from cord blood units that are considered unsuitable for banking (e.g., samples with low cell count), this may not remain the case if research using these samples proves fruitful. The therapeutic potential of such samples should therefore be clearly presented to donors as research evolves, since increased personal utility of the sample may influence a donor’s decision to donate to research. For consent to be “informed,” full disclosure of any information that may affect a donor’s decision to participate should be provided. There are many aspects and elements that may be relevant, and the institutions involved must decide what material information should be included for
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
any particular research project. Moreover, information provided should be in plain language that prospective donors can understand. Donors should be given sufficient time to consider this information before a decision is made. They should be informed of possible alternatives to participate, including the right to refuse or discontinue participation. When obtaining consent for cord blood collection and use, the donor must be made aware of the purpose(s), risks, and benefits of the entire process, how samples and personal information are collected and managed in the hospital, and how samples and data are going to be used and managed by the researcher. To obtain a robust and prospective consent for cord blood donation, several key disclosure elements have been identified.14,15 The minimum requirements for consent generally include awareness that donation is voluntary; the donor is aware of their options (discard, donate for research, public banking, private storage); permission is given for sample testing and any required disclosure of results (e.g., tests for communicable/infectious diseases); the donor agrees to provide family history and to be contacted in the future; and the donor is notified of safeguards to protect privacy and confidentiality (including traceability measures). One area of informed consent that has ethical and legal implications for the research use of cord blood in particular is the need to ensure that donors are aware of the commercial potential of their donation, because commercialization may alter their willingness to donate to research.16 Awareness of commercial potential extends beyond the notification that financial benefits will not be realized by the donor (i.e., mother or child), as described above in the context of inducements. Since donors in public banks are primarily giving samples altruistically for the treatment of others, they should be informed that cord blood (and derivate materials) may be used for commercial purposes, and while the donor will not have legal or financial interest in any resulting commercial development or patents, there is the potential for researchers or companies to generate profits from samples used in commercial applications. Lastly, “ongoing” consent implies that the consent process does not end once the consent forms are signed. Researchers have a duty to inform donors of any new information that may influence their decision to participate. Donors must also be aware of the option to withdraw consent. Withdrawal should come without disadvantage or reprisal, and conditions under which samples or data cannot be withdrawn should be clearly outlined. It should be noted that the window of opportunity to withdraw from a
research project after collection of the cord blood sample may be small, particularly if the sample is distributed to researchers fresh (i.e., not frozen). However, one overarching question that needs to be answered in any banking system is this: when should consent be obtained? This has been a controversial issue, as outlined by Broder et al.17 Requiring consent to be obtained during the prenatal period has been used as a mechanism to ensure that consent is truly informed. It gives expectant parents time to consider the information and to ask questions before the onset of labour. While this practice is generally considered ideal, it effectively denies access to women who do not receive prenatal care or who have not been exposed to educational or promotional material regarding public cord blood banking. As a result, it limits ethnic representation and genetic diversity in banked samples. Many banks therefore are changing their policies, and are allowing either a one-time or a phased consent process (separating the consent for collection of the cord blood from the consent for testing, banking, and for research and/or therapeutic uses) to be initiated during hospital admissions in the early stages of labour.18 2. Privacy
Privacy refers to “an individual’s right to be free from intrusion or interference” with respect to their “bodies, personal information, expressed thoughts and opinions, personal communications with others, and spaces they occupy.”13 It calls for individual and institutional requirements for confidentiality (the duty to safeguard information) and security (measures to protect information).13 In the context of cord blood donation and research, privacy applies to the donation itself and the management of subsequent information and data from the mother and her baby. Institutions collecting and managing cord blood need to ensure their staff and collaborators are familiar with their privacy and confidentiality obligations. Decisions must also be made regarding the donor information that will be required and used in biomedical research and how to safeguard donor information securely. One key research issue is that of sample traceability. As described by Sugarman et al.,19 samples to be used in transplantation generally remain linked to information about the donor. Linkage of samples to donor information allows samples to be identified if at a future date the donor was found to have a genetic or infectious disease that could be transmissible through the sample. However, this linkage also comes with risks to privacy of the donor. While safety implications may outweigh the privacy concerns in the context of cord blood banking for transplantation, this is not necessarily the case for biomedical research use. MAY JOGC MAI 2015 l 447
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To protect donor privacy, coding or de-identification of samples is generally recommended in research applications, in particular where samples and information may be used in studies whose details have not been specified or may be shared internationally. 3. Governance
The essence of governance is its focus on mechanisms that foster, among other important issues, accountability, transparency, legitimacy, stewardship, and public trust. Governance is generally conceived as the efficient management of organizations and activities. It requires that stem cell banks implement “structures, processes and bodies” that are “independent, accountable, and transparent” in order to ensure “scientific and ethical integrity.”20 In application, it works “at two levels: at the internal level through mechanisms governing the day-today activities of the bank, and at the external level, by independently assessing the overall bank performance and making the bank accountable to all its stakeholders.”20 In research using cord blood, it is important that each of the relevant stakeholders involved in collection, processing, storage, and clinical and biomedical research are represented in governing processes and structures. REBs play an integral part in the governance of research activities by ensuring governance mechanisms are in place and systems are transparent. In order to fulfill this role effectively, REBs and other governance bodies which fulfil review and oversight duties must be separate from and independent of bodies responsible for management and funding of the bank and research programs.20 This type of stewardship is required for research activities to maintain their integrity and sustain public support. Furthermore, to ensure that public benefit is realized from publicly supported research endeavours, the publication of research results and registration of clinical trials is recommended or required by funding agencies13 and professional organizations.21 CANADIAN NORMATIVE DOCUMENTS
The last goal of the Primer is to identify the government agencies and professional organizations that provide normative and ethical guidance on cord blood donation and use in Canada (Table). As stated in the Primer: “REBs should be aware of the norms presented in these documents, how they apply to research, and when necessary use them as resources to aid in decision making.” A number of the documents developed by these agencies and organizations directly address and make recommendations specific to ethical considerations related to cord blood collection and use. 448 l MAY JOGC MAI 2015
A key government text is the Tri-Council Agencies’ TCPS2,13 a foundational document guiding REB review of research projects. It outlines mandatory requirements and provides guidance for the ethical conduct of research, covering many areas relevant to the use of cord blood (e.g., ethics review, consent, privacy and confidentiality). It also contains provisions specific to the use of materials related to human reproduction, which includes cord blood. Also familiar to many REBs is the Canadian Institutes of Health Research publication “Updated Guidelines for Human Pluripotent Stem Cell Research,”22 which offers specific guidelines for the use of cord blood in the derivation of pluripotent stem cells. It outlines unique consent and research requirements, such as (in some cases) Stem Cell Oversight Committee review and the consent of both parents (if relevant). Documents from professional organizations should also play a role in ethical deliberation by REBs. The Society of Obstetricians and Gynaecologists of Canada’s Clinical Practice Guideline “Umbilical Cord Blood Banking: Implications for Perinatal Care Providers,”23 and various policies24 and research projects10 funded by the Stem Cell Network address the ethical collection and use of cord blood. These documents address issues such as donor recruitment, timing and scope of consent, disclosure of test results, and publication of research results. Both also highlight the importance of public (versus for-profit) cord blood banks in therapeutic and research use of cord blood. In its conclusion, the Primer acknowledges that further work must be done to address various remaining questions and to ensure that REBs are harmonized in their decisionmaking. Areas that may require further research and analysis include •• consideration of whether a centralized ethics review system would more efficiently and consistently review research projects utilizing samples from a national cord blood bank; •• exploration of the experiences of women in Canada who have donated cord blood and how the system can be optimized to meet their needs and preferences; •• examination of the role and requirements for paternal consent, and particularly how to reconcile the CIHR requirement that permission must be obtained from both parents for pluripotent stem cell research using cord blood with international guidelines which only require consent from mothers for cord blood banking; •• review of the legal conceptualization of “ownership” or “custodianship” of cord blood in Canada, and what impact this has on the rights, obligations, and liabilities of the children, parents, banks, and researchers; and
Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective
Key Canadian organizations and their documents Organization
Documents
Health Canada (HC) HC is tasked with ensuring medical products available in Canada meet appropriate quality and safety standards.
Food and Drug Act (FDA): Enabling legislation. Safety of Human Cells, Tissues and Organs for Transplantation Regulations (CTO Regulations): outlines the responsibilities that establishments that distribute or import cells and tissues for transplantation must follow to ensure product safety. Food and Drug Regulations (FDR): outlines the requirements for drug products to obtain authorization for sale and use in Canada.
Public Health Agency of Canada (PHAC) PHAC is responsible for public health at the national level, including protecting Canadians from infectious diseases.
Human Pathogens and Toxins Act (HPTA): establishes a safety system to protect the public from risks posed by substances that may contain a pathogen, such as blood products. Canadian Biosafety Standards and Guidelines (CBSG): outlines the requirements for research facilities where infectious material or toxins for non-medical use are handled or stored, and provides guidance on how those requirements are to be achieved.
The Tri-Council Agencies Canada’s three research funding agencies—the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council, and the Social Sciences and Humanities Research Council
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS2): guidelines for ethical conduct in research involving humans, required standards for organizations who receive funding from any of the three agencies.
Canadian Institutes of Health Research (CIHR) CIHR is the primary funding agency for health research in Canada, and monitors research involving human pluripotent stem cells.
Guidelines for Human Pluripotent Stem Cell Research (the Guidelines): guidelines for research involving stem cells generated from human embryos, as well as the study of pluripotent stem cell lines from other sources, including umbilical cords and placentas.
Society of Obstetricians and Gynaecologists of Canada (SOGC) SOGC is composed of health professionals who form a leading authority on reproductive health care.
Clinical Practice Guidelines: guidelines for prenatal care providers regarding the counselling, procedural, and ethical implications of cord blood banking.
Stem Cell Network (SCN) SCN, by facilitating collaborations, acts as a “catalyst for Canadian research that translates stem cell research into new therapies, commercial products and public policy.”25
SCN has developed a Public Policy & Ethical, Legal and Social Issues research program, generated policy papers, and funded academic research on a range of topics including the use of cord blood for research.
•• discussion of the role of hybrid and private cord blood banks, particularly with respect to the conditions for samples collected from such banks to be ethically transferred and used by bona fide researchers. CONCLUSION
In addition to developing a framework to provide the biomedical research community with a large, consistent source of ethically derived cord blood cells for research that may lead to potential clinical and commercial applications, Canadian Blood Services has supported the development of educational tools to ensure that the systems created are effectively and ethically implemented and managed. These tools were designed to provide information to expectant parents and REBs in particular, but can serve as educational material for broader groups. For this reason, the Primer was written to be accessible to the general public and may serve a broader purpose to increase public awareness of cord blood banking and the policies and procedures public systems are putting in place to protect donors. As the NPCBB matures, its role in facilitating cord blood research and the research
processes described above may also evolve. The Primer can be easily updated and downloaded from the Internet, and will serve as a tool to keep the general public aware of these changes. In addition, the Primer highlights the ethical and legal issues germane to the research use of cord blood samples globally: informed consent, privacy, and governance. Although developed for the Canadian context, the Primer can serve as a model for other countries to achieve similar goals. Through it, we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research. ACKNOWLEDGEMENTS
The authors would like to thank the members of the Canadian Blood Services Cord Blood for Research project team for their input. This project was supported by a grant from Canadian Blood Services and the Stem Cell Network of Canada. The views expressed here are solely those of the authors and do not necessarily represent the views of Canadian Blood Services or the Stem Cell Network. MAY JOGC MAI 2015 l 449
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