2.3 Procurement and Informed Consent of Human Biological Materials
The procurement of human gametes, embryos, fetal tissues, and somatic cells is integral to the conduct of human embryo and stem cell research. Human biological materials must be procured in accordance with generally accepted principles of research ethics and laws and policies in their respective jurisdictions.
2.3.1 Review Process for the Procurement of Human Cells and Tissues
Recommendation 2.3.1. The review process for the procurement of human cells and tissues should be predicated on the source of the material and its intended use as described in the three tiers below.
Tier 1. Banked and historical cell lines. The procurement of cell lines from repositories or banks is permissible if the materials have been deposited and distributed consistent with the original consent for use of the donated human cells and tissues and these guidelines (see Section 2.4, Derivation, Banking and Distribution of Human Stem Cell Lines) and the standards at the time (Sugarman et al. 2008). Toward this end, the repositories or banks should require certification from depositors confirming the ethical provenance of such cells, including consent and ethics approvals. The use of historical cell lines from pathological specimens, such as HeLa, are permissible for use in stem cell research that is otherwise compliant with these guidelines. Likewise, stem cell lines procured from vendors are permissible for stem cell research, provided the vendor generated and distributed the stem cell lines in a manner consistent with the original donor consent and contemporaneous ethical and regulatory standards. The procurement of Tier 1 cell lines should not be used for reproductive purposes.
Tier 2. Fresh human somatic cells and tissues. The procurement of fresh human
somatic cells and tissues for stem cell research purposes should be reviewed by existing research review committees bolstered by stem cell specific expertise in accordance with generally accepted principles of research ethics and laws and regulations in the respective jurisdiction and these guidelines (see Sections 2.3.2 and 2.3.3).
Tier 3. Gametes and embryos. The procurement of human gametes and embryos that are destined for use in human embryo research and stem cell research must be reviewed through the specialized oversight process and existing research review committees in accordance with generally accepted principles of research ethics and laws and regulations in the respective jurisdiction and these guidelines (see Sections 2.3.2 and 2.3.3).
Review by a specialized oversight process (Tier 3) or existing research review committee bolstered by stem cell-specific expertise must ensure that vulnerable populations are not exploited due to their dependent status or any compromised ability to offer voluntary consent and that there are no undue inducements or other undue influences for the provision of human cells and tissues.
2.3.2 Informed Consent for the Donation of Human Cells and Tissues
Recommendation 22.214.171.124: Embryos, fetal tissue, and other cells and tissues should be used in research only if voluntary informed consent was obtained from the donors before the research commences. The informed consent process should be robust and document the prospect of therapeutic and commercial applications as well as the potential research uses, such as the creation of hESCs, iPSCs, other immortalized cell lines, embryos, and gametes. In the case of fetal tissue, consent from the woman donating the tissue is sufficient. In the case of embryos made with donor gametes, this consent should be obtained from the gamete donors and the party(ies) with authorization to donate the embryo.
Most patients and research subjects may donate cells or tissues with broad consent to a range of future uses; however, the broad consent does not apply to use of donated cells and tissues for reproductive purposes. The consent may be obtained at the time of tissue collection or with a re-contact for additional consent to use donated cells and tissues for reproductive purposes.
In the case that human cells and tissues are procured from a minor or adult that lacks the decision-making capacity to provide informed consent, consent must be provided by a parent, legal guardian, or other legally authorized person. Whenever feasible, the assent of the minor or decisionally incapacitated adult is also strongly encouraged.
Empirical research has shown that informed consent is most effective as a dynamic, interactive, and evolving process as opposed to a static, one-time disclosure event (Flory and Emanuel, 2004). The informed consent document alone can never take the place of a meaningful dialogue between the person obtaining consent and the donors of human cells and tissues. The informed consent process can be enhanced in the following ways:
- Whenever possible, the person conducting the informed consent dialogue should have no vested interest in the research protocol. If members of the research team participate in the informed consent process, their role and any other potential conflicts of interest must be disclosed, and care taken to ensure that information is provided in a transparent, accurate, unbiased manner.
- The person conducting the informed consent process should provide ample opportunities for cell and tissue donors to ask questions and discuss their involvement in the research protocol.
- Counseling services should be made available upon request to any potential providers of human cells and tissues prior to procurement.
- Consent processes and documents should be revised in light of new research on informed consent for all types of human biological materials procurement and where relevant, ongoing studies of the long-term risks associated with oocyte retrieval.
Separating Research Consent from Treatment
Recommendation 126.96.36.199: Informed consent for research use must be distinct from informed consent for clinical treatment.
Decisions related to the provision of gametes or the creation of embryos for fertility treatment should be a voluntary choice that is free from undue influence by researchers who propose to use these cells in research. During the course of clinical treatment, researchers may not request that members of the fertility treatment team generate more embryos or harvest more oocytes than necessary for the patient’s optimal fertility treatment. Wherever possible, the treating infertility clinician should not be the investigator who is proposing to perform research on the procured materials.
Consistent with fetal tissue research guidelines issued by the Network of European CNS Transplantation and Restoration (NECTAR) and U.S. regulations, a woman’s decision to terminate a pregnancy must not be influenced by the possible research use of her fetus’ tissues (Boer, 1994; OHRP, 1993). Informed consent for fetal tissue procurement and research should be obtained from the woman only after her decision to legally terminate her pregnancy but before the abortion procedure, or after a spontaneous abortion. Medical procedures must not put the woman at any increased risk solely to facilitate the research use of donated fetal tissues. Clinicians obtaining informed consent and clinics at which informed consent is sought may not profit from the procurement of fetal tissues for research.
Review of Cell and Tissue Collection for Embryo and Stem Cell Research
Recommendation 188.8.131.52: Review of procurement protocols must ensure that cell and tissue donors are adequately informed about the specific aspects of their voluntary research participation.
Researchers should exercise care in seeking and obtaining informed consent from prospective donors. The informed consent process should take into account language barriers, the educational level and reading comprehension level of the research subjects, and any other impediments to good communication. Empirical research has shown that comprehension during the informed consent process improves with the use of interactive methods interaction (Flory and Emanuel, 2004). To facilitate the adoption of adequate and uniform standards of informed consent for the procurement of cells and tissues for research, the ISSCR provides template documents that can be downloaded and customized to specific protocols (Appendix 2). These sample documents will need to be customized for use in specific research studies and conform to local laws and policies.
If pluripotent stem cells are to be derived from procured cells or tissues, the informed consent document and discussion should cover information that addresses key aspects of human stem cell research, including but not limited to the fact that an immortal stem cell line could be established that is a partial or full genetic match to the cell or tissue donor and that the stem cell line could be shared with other researchers outside the institution and jurisdiction for other research purposes that may not be fully anticipated at this time. For a list of informed consent discussion points, see Appendix 3.
Recommendation 184.108.40.206: Researchers should develop a policy that states whether and how incidental findings will be provided to cell and tissue donors. This policy must be explained during the informed consent process. Cell and tissue donors should be able to choose whether they wish to receive incidental findings, if any. Reporting findings with relevance to public health may be required by law in certain jurisdictions.
During the course of research with human stem cell lines, particularly lines derived from somatic cells, investigators may discover information that may be of importance to cell and tissue donors, such as BRCA1/2 mutations. Because the net harms and benefits of disclosing incidental findings to cell and tissue donors are presently unclear, a single approach to managing incidental findings may not be appropriate across all studies and jurisdictions. When studies include a plan to disclose incidental findings to research subjects, researchers must offer a practical and adequately resourced feedback mechanism that involves donors’ physicians and, where possible, the verification of any discovered incidental findings.
For a given sample, secondary researchers should adhere to the incidental findings policies that were developed by the primary researchers (or others collecting cells and tissues) and disclosed to donors during the informed consent process.
If re-contact is required, instructions on how to report incidental findings (report to provider, researcher, institution, physician, etc.) should be specified in the material transfer agreement. Re-contact is a matter for primary research sites to manage. However, secondary researchers should be aware of the incidental findings policies of either of these responsible parties.
Successful implementation of a policy on incidental findings depends crucially on the traceability of cell line distribution. Therefore, all providers and recipients should ensure that cell lines are used under strict compliance with material transfer agreements and the regulations in the informed consent process.
Consent for De-identified Cells and Tissues
Recommendation 220.127.116.11: Researchers are encouraged to discuss the potential for genomic sequencing to connect de-identified cells and tissues to donors and their relatives during the informed consent process for the donation.
Cells and tissues donated for research are often de-identified to protect the privacy of donors. Due to advances in genomic sequencing, it may be possible for researchers to connect de-identified cell and tissue samples with donors or their relatives. Researchers are encouraged to require confidentiality when sharing genomic data that has the potential to connect donors and family members with de-identified cells and tissues.
2.3.3 Payments to Individuals Donating Cells and Tissue for Research
Recommendation 18.104.22.168: Research oversight committees must authorize all proposals to reimburse for out-of-pocket expenses to donors of embryos, sperm, or somatic cells.
Individuals who choose to provide previously stored cells and tissues for research should not be reimbursed for the costs of storage prior to the decision to participate in research. For the provision of fresh somatic cells or sperm for research, reimbursement for out-of-pocket expenses incurred by donors may be determined during the review process. For the provision of embryos or fetal tissue for research, no payment or valuable consideration of any kind beyond reimbursement of out-of-pocket expenses may be offered to donors for their procurement.
Recommendation 22.214.171.124: For the provision of oocytes for research, when oocytes are collected outside the course of clinical treatment, compensation for non-financial burdens should not constitute an undue inducement.
Because women carry particular burdens during the procurement of their gametes, their efforts should be acknowledged fairly and appropriately. At the same time, precaution is needed to avoid the potential for exploitation.
In jurisdictions where the provision of oocytes for research is legally permissible, the human subjects review committee and those responsible for conducting specialized research oversight must assess the safety and the voluntary and informed choice of women to provide oocytes for research according to the following standards:
- There should be monitoring of recruitment practices of oocyte donors to ensure that the decision of women to donate their oocytes is free of undue inducement and exploitation.
- In jurisdictions where research subjects are allowed compensation or valuable consideration for incurred non-financial burdens, the amount of financial recognition for the subject’s time, effort, and inconvenience must be reviewed to ensure that such compensation does not constitute an undue inducement.
- Compensation for oocyte providers’ time, effort, and inconvenience, if permitted by local laws and human subjects review committees, should be reasonably consistent with compensation levels for other types of research participation involving similarly invasive and burdensome medical procedures. Compensation levels should aim to acknowledge oocyte providers’ non-financial burdens incurred as a result of their research participation, such as their physical discomfort and effort.
- At no time should payments or other rewards of any kind be given for the number or quality of the oocytes that are to be provided for research.
- Oocyte procurement must be performed only by medically qualified and experienced clinicians, and frequent monitoring and dose adjustment must be used to reduce the risk of ovarian hyperstimulation syndrome.
- Due to the potential long-term effects of ovulation induction, women should undergo a limited number of hormonally induced ovarian stimulation cycles in a lifetime, regardless of whether they are induced for research or assisted reproduction. The limits should be determined by a thoughtful research review and oversight process, which should be informed by the latest available scientific information about the health risks.
- A fertility clinic or other third party responsible for obtaining consent or collecting cells or tissues should not be paid for the material obtained. It should be eligible for specifically defined cost-based reimbursements and payments for professional services. Fertility clinics should not profit from providing tissues for research.
To help guide review committees through the ethical considerations surrounding oocyte collection and financial recognition of providers’ efforts, the ISSCR Ethics and Public Policy Committee developed an advisory report outlining their deliberations on these issues (Haimes et al., 2013).