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Disclosure and management of research findings in stem cell research and banking: policy statement Prompted by an increased interest of both research participants and the patient advocacy community in obtaining information about research outcomes and on the use of their biological samples; the international community has begun to debate the emergence of an ethical ‘duty’ to return research results to participants. Furthermore, the use of new technologies (e.g., whole-genome and -exome sequencing) has revealed both genetic data and incidental findings with possible clinical significance. These technologies together with the proliferation of biorepositories, provide a compelling rationale for governments and scientific institutions to adopt prospective policies. Given the scarcity of policies in the context of stem cell research, a discussion on the scientific, ethical and legal implications of disclosing research results for research participants is needed. We present the International Stem Forum Ethics Working Party’s Policy Statement and trust that it will stimulate debate and meet the concerns of researchers and research participants alike. KEYWORDS: best practice n biorepository n embryonic stem cell n ethics n induced pluripotent stem cell n policy n return of research results

The International Stem Cell Forum (ISCF) was founded in 2003 to foster international collaboration and funding support for stem cell research [101] . Its overall aim is to promote global good practice and accelerate progress in stem cell research. ISCF’s membership consists of 21 funders of stem cell research from around the world. A key ISCF initiative is the Ethics Working Party (EWP) [102] . The EWP is an independent body mandated to review ethical policies pertaining to stem cell research. It aims to identify the different national ethical–legal and policy landscapes, to facilitate international dialog on key ethical issues and to foster shared ethical principles so as to guide the conduct of stem cell research and policy making. Prompted by an increased interest by both research participants and the patient advocacy community in obtaining information about research outcomes and on the use of their biological samples, the international community has begun to debate the emergence of an ethical ‘duty’ to return research findings. Furthermore, the refinement of whole-genome and -exome sequencing techniques, creating significant amounts of incidental findings with possible clinical significance, and genetic data, together with the proliferation of biorepositories, have further provided a compelling rationale for governments and scientific institutions to adopt prospective policies [1,2] .

A discussion on the scientific, ethical and legal implications of disclosing and managing research results (e.g., aggregate, individual or incidental) to research participants in pluri potent stem cell research (e.g., human embryonic stem cells [hESCs] and induced pluripotent stem cells [iPSCs]) and banking is needed due to the scarcity of policies addressing the particularities of these fields. Any policy approach to this matter must take into account the complexities of the stem cell field, which is characterized by a vast range of pluripotent stem cell researchrelated studies and a diversity of banking initiatives. Moreover, pluripotent stem cell lines are continuously immortalized, transformed and distributed, and this takes place in a context where cell-line misidentification continues to be a pervasive problem, altering the extent and authenticity of certain research findings [3–7] . The ISCF EWP is mandated to prospectively identify, discuss and analyze the ethical and policy issues of stem cell research. To that end, and considering the need for ethical deliberation and further policy guidance, the EWP adopts the following ‘policy statement’ on the disclosure and management of research and incidental findings in the context of pluripotent stem cell research and banking.

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Rosario Isasi*, Bartha M Knoppers, Peter W Andrews, Annelien Bredenoord, Alan Colman, Lee Eng Hin, Sara Hull, Ock-Joo Kim, Geoffrey Lomax, Clive Morris, Douglas Sipp, Glyn Stacey, Jan Wahlstrom & Fanyi Zeng; for the International Stem Cell Forum Ethics Working Party *Author for correspondence: Centre of Genomics & Policy, McGill University, QC, Canada [email protected] See back page for a full list of affiliations

General background A complex and polarized debate has evolved over the rationale for disclosing research findings to

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research participants. Seemingly, a consensus has emerged regarding an ethical ‘duty’ in certain contexts to disclose qualified research findings to participants in genetic and genomic studies [8–14] . The essential conditions for such disclosure are clinical and analytical validity, clinical utility and actionability. The criteria of analytical and clinical validity refer to a result that accurately and reliably identifies particular genetic characteristics or traits, or measures the genotype of interest. A test is clinically valid when it consistently and accurately detects or predicts the intermediate or final outcomes of interest. To be clinically useful, the result must be both clinically valid and have the potential to significantly improve patient health outcomes. Finally, a finding is actionable when it is capable of being acted on. For instance, a finding is actionable if there are established therapeutic or preventive interventions that have the potential to change the clinical course of a disease [10,15–19,103] . Such a duty to disclose, when present, should be imposed only after weighing competing principles, this includes assessing the potential benefits of disclosure against potential harms and only after specific criteria are met. Interestingly, both proponents and opponents of creating such a duty base their arguments on the same bioethical principles of autonomy (or respect for persons), beneficence and nonmaleficence [16,20,21,104] . The context in which research findings are generated has shaped the policy debates and outcomes. Indeed, it is the particular research context that determines whether an ethical – or even a legal – duty could or should be established [22] . It is of pivotal importance to distinguish between the type of research study (e.g., biobank/research donation or basic vs clinical research among others) and associated findings (e.g., general, individual or incidental) and the specific obligations of individuals and institutions at the different stages of the research cycle (e.g., primary vs secondary researchers or bio repositories among others) [23–26] . Conflation of these issues may have significant ethical, scientific and legal implications. Indeed, it has been argued that the type, duration and nature of the relationship between the research participant and the researcher (or biorepositories) [27,28] are conditions with the greatest impact on establishing such a duty [15,29] . To that end, the following sections provide an overview of the typology of research findings. We also briefly address how these issues have been dealt with in the general context of clinical, genomic and genetic research. Where applicable, comparisons with the specific context of stem cell research are made. 440

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Feedback or baseline assessment Research participants donating biological materials undergo assessment tests and measure ments prior to recruitment. In most cases, medical history and lifestyle questionnaires are also obtained. In all circumstances, results from this baseline assessment are communicated as immediate feedback and are not part of the research study per se, and as such are not considered as individual research findings. In the general clinical research context, consensus exists regarding a duty to communicate to research participants abnormal measures and critical values discovered during a baseline assessment. Critical values in the laboratory identify results that indicate the presence of a life-threatening event for which urgent and immediate medical attention is necessary. The mechanisms for such disclosures at recruitment are not the subject of the discussion that follows regarding the return of research results [17] . Nevertheless, it should be mentioned that in the specific context of stem cell research, donor eligibility determination also requires screening for risk factors associated with infection and communicable disease. Screening requirements for donors of embryos, cells and tissues vary according to national regulatory frameworks and institutional protocols. These requirements will also differ depending on the type of biological material being donated and the circumstances under which such material was initially collected (e.g., clinical care vs research). In the absence of a compelling rationale, the duty to provide feedback at baseline assessment as noted above should be transposed to the stem cell research context [30] . General research findings & public dissemination With respect to the communication of aggregate or general findings to research participants, here too, there is an emerging consensus that providing a system to support such communication constitutes best practice [20,31] . Aggregate results are typically the central findings or general conclusions arising from a particular research study. In the context of stem cell research, these may include generalized information about the nature of stem cell line use and distribution by researchers and biorepositories, together with research outcomes. Various modalities of communication have been proposed, ranging from passive methods by means of websites or newsletters to interactive communication tools [104,105] . These future science group

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systems are predicated on a robust informed consent process in which prospective donors and research participants are empowered to choose the medium of communication they prefer to receive. Offering aggregate research results is an effective mechanism to show respect and gratitude to participants, as well as promoting trust in the research enterprise [32] . Beyond the issue of communicating aggregate results lies the issue of professional responsibility. As noted by the International Society for Stem Cell Research (ISSCR), researchers have the ethical duty to communicate general research results so as to promote transparency in the field. Similarly, research participants in particular, and society in general, have the right to access such information. By promoting transparency, institutions encourage scientific and ethical integrity in research [106] . Moreover, while acknowledging potential logistical challenges, individual research projects and institutional protocols should also establish mechanisms for providing data on the usage of samples, as well as lay summaries of study protocols accessing data and samples and their outcomes. Similarly, complete research findings (whether negative, inconclusive or positive) should be published in peer-reviewed publications, and plain-language summaries should be made available to the public [33,103,105] . Individual research results & incidental findings Regarding individual research results, it is important to distinguish them from incidental findings. While both types of findings relate to an individual participant and have potential health or reproductive importance, the key distinction rests on the context in which such findings are discovered. An individual research result occurs within the research process; that is, in research relating directly to the specific aims or focal variables of a particular study. By contrast, incidental findings are unintended and beyond the aims of the study [15,34–36,103] . Similarly, it is important to highlight that any mechanism for disclosing individual research findings necessarily presupposes the identifi ability of a research participant (i.e., linkage). In the particular context of stem cell research, traceability and identifiability relates to the donor of the reproductive or somatic tissue from which the stem cell line was derived [33,37] . Such identifiability is facilitated by traceability measures, but certainly it is prevented if the stem cell lines have been anonymized future science group

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(meaning that all donors’ identifiers have been irretrievably removed). Traceability is the ability to document, identify and locate the origin of biological samples (e.g., gametes, embryos and somatic tissue) and relevant data (genealogical, phenotypic, genetic or clinical among others). Thus, traceability serves to advance participants’ interests by ensuring the safety of samples and by allowing for the possibility to communicate individual or general research results. However, in spite of the most stringent efforts to assure robust traceability, it is still not possible to guarantee that a specific data point is definitively applicable to the original donor because of the possibility of human error. Moreover, such assurance would be stronger if it were possible to show that DNA profiles (e.g., short tandem repeats) were the same in both the donor and the donor-derived cell line. Even this would not protect against genetic changes that occurred in the derived cell line, which will affect the relevance of the data to the donor [3–5] . Finally, in the context of genomic and genetic research, it has been argued that for some specific studies in which the nature of the research question is open-ended or descriptive, it may not be possible to distinguish between incidental and other types of research findings [26,36,38,39] . This is particularly important where new technologies (e.g., next-generation sequencing or single nucleotide polymorphism arrays) are being applied, given the amount and signifi cance of the data derived from the analysis. In pluripotent stem cell research, it is known that certain mutations may be common to all iPSC and hESC lines [7] and that adventitious contamination with microbial agents may also influence the data arising from these cultures. Nevertheless, it should be taken into consideration that pluripotent stem cell lines will be subject to next-generation sequencing techniques (e.g., whole-genome or -exome sequencing) and that these data may well have relevance to the donors and their families. During the derivation of pluripotent stem cell lines, the cells are known to undergo genetic changes due to mutations and other defects that may arise during cell division. Such genetic defects may also arise during extended in vitro culture and, where a growth advantage is realized in these cells, they can quickly replace the original culture [7] . Thus, data from pluripotent stem cell lines cannot be assumed to be of direct relevance to the donor unless DNA obtained directly from that donor can be used to independently confirm the findings in the respective cell line [6,7,30] . www.futuremedicine.com

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Returning research findings to research participants Empirical studies conducted to assess the views of research participants on receiving research results demonstrate that, in the context of clinical and genetic research, participants have an increased interest in obtaining general results, including information regarding the use of donated biological materials [27,28,31,40–45] . In some circumstances, research participants have indicated an interest in obtaining individual results regarding clinically significant information where prevention or treatment is available (i.e., actionable). With respect to stem cell research, there is anecdotal evidence that donors of disease-specific iPSC lines may support such individual return [46] . The discussion of whether individual research results may, should or must be offered or communicated to research participants (or not) has centered on the need for equitable mechanisms for respecting participants’ interests, while taking into account the nature of the research enterprise; that is, an endeavor aimed at producing generalizable knowledge [36,47–49] . Two underlying issues can be distilled from this still contentious debate. First is an ethical dimension grounded in the principle of autonomy (i.e., self-determination or respect for persons) and on the premise that participants have an interest in obtaining information about research outcomes, as well as individual findings of clinical significance [8,14,20,21,25,50] . A second dimension centers on the ‘duty to rescue’ or on the duty to provide ‘ancillary care’ [24,51–53] . The duty to rescue, as developed in several legal frameworks, could be summarized as the obligation to provide reasonable emergency assistance to a person in a life-threatening situation. This duty is not openended. It requires that a number of conditions be met: minimal, individual actions; evidence of clear and immediate peril requiring urgent action; and the prevention of further harm, among others [54] . Based on the principle of reciprocity (or solidarity) and on the doctrine of fiduciary duties, an ancillary care justification for disclosure of individual research findings is found in the belief that participants entrust their health to the researcher upon their enrollment in the study [32] . Consequently, it is maintained that researchers owe participants certain clinical duties where the context shifts from basic research to the clinical setting. Such an obligation does not arise from requirements for safety or redressing a participant’s injury, among others. In the context of disclosing research findings, both the emergency 442

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and ancillary care could create an ethical obligation to communicate information that could save lives [20] . By contrast, opponents of returning individual research findings to participants find solid justification in the danger of creating therapeutic misconception [55] , in conflating clinical care with research or in the possibility of harming research participants by disclosing results that lack ana lytical and clinical validity or that are not clinically useful [20,56] . Operational arguments such as creating untenable burdens on research infra structures, including creating additional, openended obligations for researchers and institutions as well as increasing costs, are cited as strong arguments to oppose the return of individual research results. Moreover, it has been noted that there is a serious danger in using the promise of returning individual findings to participants as a means of inducing participation or increasing accrual rates [16,20,24,29,57,58] . As evidenced by ethical guidelines and legal norms, an ethical ‘duty’ to disclose qualified research findings to participants in genetic and genomic studies is emerging. A consensus exists across national and international policies to the effect that an essential element of the informed consent process is the disclosure of whether general, individual or incidental findings will be communicated to research participants or not. If so, the conditions (e.g., clinical and analytical validity, clinical utility and actionability) and the mechanisms for such disclosure should be stipulated clearly in research and institutional protocols [10,12–14,20,103,105,107] . For stem cell research, and banking specifically, the scientific, ethical and legal policy implications of mandating the disclosure of individual research results, including incidental findings, have seldom been addressed. Notable exceptions are recommendations adopted by the Australian National Health and Medical Research Council [108] , the British Human Fertilization and Embryology Authority [109] , the European Group on Ethics in Science and New Technologies to the European Commission [110] and the guidelines adopted by the US National Academies of Science [111] and the California Institute for Regenerative Medicine [105] . In these guidelines, discussing the policy for handling the potential discovery of ‘clinically significant’ information and incidental findings is considered an essential element of the informed consent process. Furthermore, these policies call for primary stem cell researchers (i.e., those deriving pluripotent stem cell lines) and stem cell biorepositories to adopt prospective future science group


protocols governing the disclosure and management of such information back to donors as a way of managing stakeholder expectations.

ISCF EWP policy statement The EWP is well aware of the complexities of the stem cell field, which include a vast range of pluripotent stem cell research-related studies and a sizeable diversity of banking initiatives, wherein a wide range of pluripotent stem cell lines are continuously derived and distributed (Table 1) [6,7,30,59] . These activities should be situated in a historical context in which cell line misidentification and contamination remains pervasive [5] . For this reason, we are against a single ‘one-size-fits-all’ approach to handling the disclosure and management of general, individual and incidental research findings [16,105] . Rather, in the policy recommendations that follow, we propose a framework with criteria for future policy. Such recommendations are narrowly tailored to address stem cell lines derived from human embryos and from somatic tissue via iPSC techniques from adult donors. While recognizing local ethical and legal constraints, the EWP considers that the goal of open science and the principles of transparency, reciprocity, autonomy and beneficence argue in favor of supporting a system for communicating certain research findings to participants and donors of human biological materials. Such a system is predicated on obtaining robust and prospective informed donor consent [60] . To that end, such consent should address the possibility of donor recontact and for the communication of indivi dual research results and incidental findings that are of clinical and analytical validity, clinical utility and are actionable [33,61] . Furthermore, the ISCF EWP encourages the scientific community to prospectively adopt protocols for providing general information about the nature of stem cell line use by researchers and to publicly document such general research findings. The ISCF EWP only foresees the possible communication of individual and incidental findings for human pluripotent stem cell research (e.g., iPSC and hESC lines) as per the following discussion. As described above, returning general, indivi dual or incidental findings to research participants is necessarily predicated on the possibility of identifying and contacting the donors of the biological samples from which the stem cell line was derived. When stem cell lines have been anonymized (meaning that all donors’ identifiers have been irretrievably removed) or when the original informed consent did not foresee or inadequately addressed the possibility of donor recontact, the disclosure future science group

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of any research findings is neither feasible nor appropriate [33] . Moreover, across the typology of stem cell research and banking projects, researchers and biobankers have agreed to respect privacy and consequently not to attempt to reidentify sample donors. This obligation forms part of the informed consent process, and is also part of the material transfer agreement for access to resources adopted between researchers and biorepositories. Consequently, any policy or protocol addressing the potential disclosure of research and/or incidental findings must clearly articulate and distinguish between the roles and responsibilities of primary and secondary researchers, as well as biorepositories. Similarly, such policies must be tailored to the nature of research participation (e.g., biological sample donor vs clinical trial participant). Such policies should also take into account the significant implications (e.g., financial, ethical, legal and scientific among others) of extending a duty to disclose certain research and incidental findings beyond primary researchers [22,33,61] . In the context of pluripotent stem cell research (Table 1) , where the return of individual research results and incidental findings are warranted and supported by informed donor consent, protocols comprehensively detailing the nature of such findings, the mechanisms for disclosure and their management should be established prior to obtaining consent to donate. These processes should be transparent with regard to the conditions for such context-specific and qualified disclosure [48] . Moreover, such protocols should be tailored to reflect the diversity of pluripotent stem cell lines and the typology of stem cell research studies and biorepositories. Most importantly, they should recognize and respect the specific needs and interests of the particular donor population involved (i.e., children/minors, affected individuals, adults who lack the capacity to consent or healthy volunteers) [105] . However, at this time, given the nature of hESC lines (Table 1) and the circumstances of their derivation, we caution against any return of donor-specific results (whether research or incidental) to embryo and gamete donors. hESC lines are derived from embryos created largely in the clinical context of assisted reproduction or in vitro fertilization treatments (i.e., for reproductive purposes). In some circumstances they have been derived from embryos created via third-party gamete donation. Moreover, an important issue to take into consideration is the fact that hESC lines bear the contribution and characteristics of two genetically different individuals. While, for instance, mechanisms for www.futuremedicine.com

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Table 1. Scientific considerations for cells and tissues. Primary somatic cells and tissue

Reprogrammed somatic cells (iPSCs)

Human embryonic stem cells

Source

Individual ‘adult’ somatic cells

Common source is individual ‘adult’ somatic cells Potential source of gametes

Human haploid gametes

Genetic (DNA) characteristics

Donor-specific DNA and DNA products Genetic/epigenetic profile not changed There may be changes and even progressive phases of change in inherited genetic disorders, and potential cancer cells might be present in normal tissue (e.g., donor-associated leukemia in bone marrow transplant recipients)

Donor-specific DNA Reprogramming alters epigenetic profile DNA and/or DNA products may be altered by reprogramming, with differences according to specific protocols

DNA contribution from two donors. However, mechanisms of Mendelian inheritance will still apply Relationship between DNA and/or DNA products and donors is uncertain

Considerations for clinical/scientific validity of research findings

Because cells are not manipulated or transformed, genetic/biological assays are considered valid for diagnostic purposes

Cells have the capacity for unlimited replication/expansion Through gene insertion and reprogramming processes, there may be changes in the methylation of cells. Consequently, the validity of diagnostic tests is uncertain Some findings may be valid and of clinical significance to the donor/donor family, but further validation of assays would be required through confirmatory testing of the source Confirmatory testing must be performed on the source (primary sample from individual donor)

Some findings may be valid and of clinical significance to donors/donor families, but further validation of assays would be required through confirmatory testing Confirmatory testing must be performed on the source (primary sample from individual donor) Currently, such testing is not valid for drawing inferences to the donors Testing is only considered valid for diagnosis in the embryo per se

iPSC: Induced pluripotent stem cell.

Mendelian inheritance will still apply, changes occurring during the cell line derivation process (e.g., DNA mutation, changes in the methylation of cells or acquisition of karyotypic changes and other mutations) could alter the significance or relevance of some findings for a particular donor(s) [3,6,7,30,45] .

Policy recommendations Return of general research findings Where feasible, and provided appropriate donor consent has been sought, generalized information about the nature of stem cell line use by researchers and biorepositories in the form of aggregate research findings should be communicated to research participants via predefined mechanisms (e.g., websites, bulletins or letters among other methods). Protocols should clearly delineate the scope of the responsibilities (if any) imposed on primary or secondary researchers and biorepositories. Return of individual research results & incidental findings For pluripotent stem cell lines, if the protocol foresees the return of individual research results 444

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and incidental findings, the EWP recommends that the following elements be considered in a return of results policy: The donor has been offered and has consented to their return; The results or findings are analytically and clinically validated, have clinical utility and are actionable; Any genetic information derived from the stem cell line has been confirmed by analysis of a verifiable DNA sample from the original donor(s); The protocol comprehensively and clearly describes the mechanisms and conditions for disclosure, including the scope of the responsibilities imposed on researchers (whether primary or secondary) and/or biorepositories and the health professional(s) charged with such disclosure; The protocol for disclosure has been approved by an oversight committee or by an independent ethics review committee. future science group


Conclusion & future perspective Our ethical and policy deliberation together with the ensuing policy recommendations provide a foresight approach to the debate regarding the disclosure and management of research findings (general, individual or incidental) in the context of stem cell research and banking. By providing context-specific ethical and policy guidance and taking into account the complexities of the stem cell field, the ISCF EWP trusts that this policy will stimulate debate. Hopefully, it will also address the concerns of researchers, policy-makers, patients and research participants alike. We propose a framework with criteria for future policy based on the principled foundations of transparency, autonomy, reciprocity and beneficence. Now that the debate has begun, the task ahead is to assess and document stakeholders’ perspectives via robust empirical studies. Is there continued support for communicating research findings to participants and donors of biological materials?

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If so, what would be the essential elements for a more systemic approach? Disclaimer The opinions expressed in this manuscript are those of the authors alone. No statement in this article should be construed as an official position of the National Human Genome Research Institute, NIH or Department of Health and Human Services.

Financial & competing interests disclosure This project was supported, in part, by the International Stem Cell Forum (Ethics Working Policy) and the Stem Cell Network of Canada (R Isasi and BM Knoppers). The authors’ funding sources have played no role in the design, interpretation or writing of the present study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript

Executive summary Background Consensus has emerged over an ethical ‘duty’ to disclose qualified research findings (general, individual and/or incidental) to participants in genetic and genomic studies. The essential conditions for such disclosure are clinical and analytical validity, clinical utility and actionability. ‘Duty to disclose’, which is context-dependent, should be imposed only after weighing competing principles (e.g., autonomy, beneficence, nonmaleficence and so on) – and assessing the potential benefits of disclosure against potential harms. Returning research findings to research participants Empirical studies conducted to assess the views of research participants on receiving research results suggest that participants have an increased interest in obtaining general research results, and in some instances, individual and incidental findings. Debate on whether individual research results may, should, or, must be offered or communicated to research participants (or not) has centered on the principles of autonomy and reciprocity, as well as on the duties ‘to rescue’ or to provide ‘ancillary care’. Opponents of returning individual research findings to participants base their arguments on the danger of creating therapeutic misconception and in the possibility of harming research participants. The International Stem Cell Forum Ethics Working Party policy statement Recognizing local ethical and legal constraints, the Ethics Working Party (EWP) considers that the goal of open science and the principles of transparency, reciprocity, autonomy and beneficence argue in favour of supporting a system for communicating certain research findings to participants and donors of human biological materials. The International Stem Cell Forum EWP encourages the scientific community to prospectively adopt protocols for providing general information about the nature of stem cell line use by researchers and to publicly document such general research findings. Given the nature of human embryonic stem cell lines and the circumstances of their derivation, the International Stem Cell Forum EWP cautions against any return of donor-specific results (whether research or incidental) to embryo and gamete donors. For pluripotent stem cell lines, if the protocol foresees the return of individual research results and incidental findings, the EWP recommends that the following elements be considered in a return of results policy: – The donor has been offered and has consented to their return; – The results or findings are analytically and clinically validated, have clinical utility and are actionable; – Any genetic information derived from the stem cell line has been confirmed by analysis of a verifiable DNA sample from the original donor(s); – The protocol comprehensively and clearly describes the mechanisms and conditions for disclosure, including the scope of the responsibilities imposed on researchers (whether primary or secondary) and/or biorepositories and the health professional(s) charged with such disclosure; – The protocol for disclosure has been approved by an oversight committee or by an independent ethics review committee.

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Policy Focus


Affiliations

Rosario Isasi Center of Genomics & Policy, Faculty of Medicine, Department of Human Genetics, McGill University, Montreal, QC, Canada Bartha M Knoppers Center of Genomics & Policy, Faculty of Medicine, Department of Human Genetics, McGill University, Montreal, QC, Canada

Peter W Andrews Department of Biomedical Science, University of Sheffield, Sheffield, UK

Annelien Bredenoord Julius Center, Department of Medical Ethics, University Medical Center Utrecht, Utrecht, The Netherlands

Alan Colman Singapore Stem Cell Consortium, Institute of Medical Biology, Singapore

448

Lee Eng Hin Division of Graduate Medical Studies, Faculty of Medicine, National University of Singapore, Singapore

Sara Hull NHGRI Bioethics Core, NIH, MD, USA

Ock-Joo Kim Department of Medical History & Medical Humanities, College of Medicine Seoul National University, Seoul, Korea

Geoffrey Lomax California Institute for Regenerative Medicine, CA, USA

Clive Morris National Health & Medical Research Council, Canberra, Australia

Douglas Sipp Research Unit for Science Policy & Ethics Studies, RIKEN Center for Developmental Biology, Kobe, Japan

Regen. Med. (2012) 7(3)

Glyn Stacey Division of Cell Biology & Imaging, National Institute for Biological Standards & Control, UK Stem Cell Bank, Potters Bar, UK

Jan Wahlstrom Department of Medical Genetics, University of Gothenburg, Göteborg, Sweden

Fanyi Zeng Shanghai Institute of Medical Genetics, Shanghai Stem Cell Institute, Shanghai, China

International Stem Cell Forum Ethics Working Party McGill University & Génome Québec Innovation Center, 740 Dr Penfield, Suite 5206, Montreal, QC, H3A 1A4, Canada
