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TCPS 2 - Chapter 12

HUMAN BIOLOGICAL MATERIALS INCLUDING MATERIALS RELATED TO HUMAN REPRODUCTION

Introduction
A. Types of Human Biological Materials
B. Collection of Human Biological Materials
C. Consent and Secondary Use of Identifiable Human Biological Materials for Research Purposes
D. Storage and Banking of Human Biological Materials
E. Research Involving Materials Related to Human Reproduction
F. Research Involving Pluripotent Stem Cells

Introduction

The use of materials originating from human bodies for research contributes greatly to the advancement of knowledge. The sources of these materials can be from patients following diagnostic or therapeutic procedures, autopsy specimens, donations of organs or tissue from living or dead humans, body wastes (including urine, saliva, sweat) or abandoned tissue. Biological materials may also be sought from individuals for use in a specific research project. Once collected, biological materials may be held in biobanks to serve as a research resource for many years.

Ethical considerations raised by research involving human biological materials centre on acceptable access to, and use of, the materials, potential privacy concerns arising from the handling of information derived from such materials, and the special status some individuals and groups accord to the human body and its parts. Because the significance of biological materials varies among individuals and groups, it is important to assess the ethics of research involving such materials with an awareness of and sensitivity to the known values, beliefs and attitudes of those from whom the materials originated.

Sections A to D of this chapter provide guidance on research involving human biological materials.For the purposes of this Policy, human biological materials include tissues, organs, blood, plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva and other body fluids. Section E addresses research involving the subset of biological materials that are related to human reproduction. Section F addresses research involving the subset of human biological materials known as human pluripotent stem cells, animal-human hybrids and chimeras.

As noted in Chapter 2, an individual whose data and/or biological materials are used in research becomes a participant.In regard to human biological materials, individuals may become participants by agreeing to provide a biological sample for use in a particular project. Individuals may also choose to donate organs, tissue or their entire body for research that occurs after their death.In this way, they become participants through their donation. Researchers may seek access to human biological materials for secondary use in research and, in accordance with Section C of this chapter, a research ethics board (REB) may waive a requirement for individual consent.

A. Types of Human Biological Materials

Human biological materials that may reasonably be expected to identify an individual, alone or in combination with other available information, are considered identifiable biological materials (or biological materials that are identifiable) for the purposes of this Policy. The following categories, similar to those found in Chapter 5 in regard to categories of information, provide guidance for assessing the extent to which human biological materials could be used to identify an individual:

  • Identified human biological materials – the materials are labelled with a direct identifier (e.g., name, personal health number). Materials and any associated information are directly traceable back to a specific individual.

  • Coded human biological materials – direct identifiers are removed from the materials and replaced with a code. Depending on access to the code, it may be possible to re-identify specific individuals (e.g., a principal investigator retains a key that links the coded material with a specific individual if re-linkage is necessary).

  • Anonymized human biological materials – the materials are irrevocably stripped of direct identifiers, a code is not kept to allow future re-linkage, and risk of re-identification of individuals from remaining indirect identifiers is low or very low.

  • Anonymous human biological materials – the materials never had identifiers attached to them and risk of identification of individuals is low or very low.

Due to continuing technological development in genetics, individuals with access to stored human biological materials are increasingly able to use genetic markers to link a non-identifiable sample with an identified sample. For this reason, genetic analysis has made it more difficult to categorize human biological materials as anonymous or anonymized. The definitions above relate to identification of individuals; however, some research involving human biological materials, especially genetic research, may involve identification of groups, even though the human biological materials are non-identifiable at an individual level. Researchers and REBs should be aware of, and guard against, threats to individual privacy and autonomy that arise from re-identification risks, as well as risks to groups, particularly where sensitive research findings will be linked to specific groups.

To maintain confidentiality, it may seem desirable to use anonymized or anonymous human biological materials. However, the scientific requirements of many studies may necessitate use of identifiable human biological materials, to link materials with information about participants, and to avoid using different samples from the same individual. Use of anonymized or anonymous human biological materials has the disadvantage of making it impossible to offer the benefits of research findings to participants and their families, or to alert them to relevant clinical findings. This is particularly significant when research may disclose a previously undiagnosed condition, such as HIV infection or an inherited predisposition to breast cancer, for which potentially effective treatments are available. Use of non-identifiable human biological materials also precludes withdrawal of a participant’s material from research use, even at the participant’s request.

B. Collection of Human Biological Materials

Human biological materials may be obtained in different ways:

  1. they may be collected expressly for a specific research purpose;

  2. they may be collected incidentally to medical or diagnostic procedures with no initial intent to be used in research; or

  3. they may be collected for research or medical or diagnostic purposes with some expectation that they may, or will, also be used in future research, although the precise research project(s) may not be known at the time.

The first category above refers to the initial collection of human biological materials for research, which is described in this section. The latter two categories are relevant to subsequent, secondary uses of human biological materials for research that may not have been conceived at the time the tissue was taken. Secondary use of biological materials is described in Section C.

Article 12.1  Research involving collection and use of human biological materials requires REB review and:

(a) consent of the participant who will donate biological materials; or

(b) consent of an authorized third party on behalf of a participant who lacks capacity, taking into account any research directive that applies to the participant; or

(c) consent of a deceased participant through a donation decision made prior to death, or by an authorized third party.

Application  Article 12.1 applies prospectively, that is, prior to the collection of human biological materials for research purposes. It applies the general elements of consent in Chapter 3 to the collection and use of human biological materials. During the consent process,a clear distinction should be made between consent to research participation and consent for any clinical procedure or test. In practice, this may mean separate consent information and forms, but in any event the different uses must be clearly explained. Individuals who do not wish to contribute human biological materials for research are free to withhold consent without penalty, and without prejudicing access to any treatment they would otherwise receive. For individuals who lack capacity to consent, the guidance developed in Chapter 3 regarding authorized third parties shall be observed.

Where a participant has expressed preferences for future research participation in a research directive before losing capacity, researchers and authorized third parties shall take such directives into account during the consent process. Chapter 3 provides guidance on research directives.REBs and researchers should be aware that provincial human tissue gift laws may provide a legal framework for the donation of tissue upon death.

Article 12.2  To seek consent for use of human biological materials in research, researchers shall provide to prospective participants or authorized third parties,applicable information as set out in Article 3.2 as well as the following details:

(a) the type and amount of biological materials to be taken;

(b)  the manner in which biological materials will be taken, and the safety and invasiveness of the procedures for acquisition;

(c)  the intended uses of the biological materials, including any commercial use;

(d)  the measures employed to protect the privacy of and minimize risks to participants;

(e)  the length of time the biological materials will be kept, how they will be preserved, location of storage (e.g., in Canada, outside Canada), and process for disposal, if applicable;

(f)  any anticipated linkage of biological materials with information about the participant; and

(g)  the researchers’ plan for handling results and findings, including clinically relevant information and incidental findings.

Application  Chapter 3, especially Article 3.2, provides detailed guidance on the need for consent to participation in research. Article 12.2 provides additional guidance on information that prospective participants generally require to make an informed decision to donate biological materials for use in research. While all the basic guidelines of Chapter 3 regarding consent apply to research involving human biological materials, some deserve special attention. For example,explaining the potential for commercialization or financial conflict of interest is important, as some research with human biological materials may involve the possibility of significant commercial gain for researchers or sponsors. The process for requesting withdrawal of human biological materials from research shall also be clearly explained, along with an explanation of the conditions under which researchers would not be able to remove a participant’s data from the project. For instance, where participants request the withdrawal of their biological materials, information already derived from the materials and aggregated into findings cannot be withdrawn. Anonymization of human biological materials may also preclude subsequent withdrawal. Chapter 3 provides further guidance on handling incidental findings.

C.  Consent and Secondary Use of Identifiable Human Biological Materials for Research Purposes

Chapter 5 provides detailed guidance on secondary use of information for research purposes (in particular, see Articles 5.5 and 5.6). The following section adapts the provisions in Chapter 5 to the specific context of research involving secondary use of human biological materials. As researchers who seek to use human biological materials for research will often also seek access to information about individuals from whom the materials originate, this section and Chapter 5 should be read together.

Secondary use refers to the use in research of human biological materials originally collected for a purpose other than the current research purpose. A researcher may seek to use human biological materials left over from a diagnostic examination or surgical procedure, or materials that were collected for an earlier project. Reasons to conduct secondary analyses include: avoidance of duplication in primary collection and the associated reduction of burdens on participants; corroboration or criticism of the conclusions of the original research; comparison of change in a research sample over time; application of new tests of hypotheses that were not available at the time of original collection; and confirmation that the data or materials are authentic. Privacy concerns and questions about the need to seek consent arise, however, when human biological materials provided for secondary use in research can be linked to individuals, and when the possibility exists that individuals can be identified in published reports, or through linkage of human biological materials with other data.

Article 12.3  Researchers who have not obtained consent from participants for secondary use of identifiable human biological materials shall only use such material for these purposes if the REB is satisfied that:

(a) identifiable human biological materials are essential to the research;

(b) the use of identifiable human biological materials without the participant’s consent is unlikely to adversely affect the welfare of individuals from whom the materials were collected;

(c) the researchers will take appropriate measures to protect the privacy of individuals and to safeguard the identifiable human biological materials;

(d) the researchers will comply with any known preferences previously expressed by individuals about any use of their biological materials;

(e) it is impossible or impracticable to seek consent from individuals from whom the materials were collected; and

(f) the researchers have obtained any other necessary permission for secondary use of human biological materials for research purposes.

If a researcher satisfies all the conditions in Article 12.3(a) to (f), the REB may approve the research without requiring consent from the individuals from whom the biological materials were collected.

Application  This Policy does not require that researchers seek consent from individuals for the secondary use of non-identifiable human biological materials. In the case of the secondary use of identifiable human biological materials, researchers must obtain consent in accordance with applicable laws, unless the researcher satisfies all the requirements in Article 12.3.

The exception to the requirement to seek consent in this article is specific to secondary use of identifiable human biological materials. The terms of Article 3.7 address alteration of consent in other circumstances and do not apply here.

Secondary use of human biological materials identifiable as originating from a specific Aboriginal community, or a segment of the Aboriginal community at large, is addressed in Articles 9.20 to 9.22.1

“Impracticable” refers to undue hardship or onerousness that jeopardizes the conduct of the research; it does not mean mere inconvenience.2 Consent may be impossible or impracticable when the group is very large or its members are likely to be deceased, geographically dispersed or difficult to track. Attempting to track and contact members of the group may raise additional privacy concerns. Financial, human and other resources required to contact individuals and seek consent may impose undue hardship on the researcher. In some jurisdictions, privacy laws may preclude researchers from using personal information to contact individuals to seek their consent for secondary use of information.

At the time of initial collection, individuals may have had an opportunity to express preferences about future uses of their biological materials, including research uses (see paragraphs (d) and (i) in the Application of Article 3.2). Custodians that hold human biological materials have an obligation to respect the individual’s expressed preferences. Where an individual does not want biological materials used for future research, custodians should remove these biological materials from any collections used or made available for research. Alternatively, individuals may have made an express donation of biological materials for research in accordance with human tissue gift legislation.

In cases where the proposed research involves issues of greater sensitivity (e.g., research involving stigmatizing conditions), an REB may require that researchers engage in discussion with people whose perspectives can help identify the ethical implications of the research, and suggest ways to minimize any associated risks. Discussion is not intended to serve as proxy consent. Rather, a goal of discussion is to seek input regarding the proposed research, such as the design of the research, measures for privacy protection, and potential uses of findings. Discussion may also be useful to determine whether the research will adversely affect the welfare of individuals from whom the biological materials were collected. Researchers shall advise the REB of the outcome of such discussions. The REB may require modifications to the research proposal based on these discussions.

Article 12.4  When secondary use of identifiable human biological materials without the requirement to seek consent has been approved under Article 12.3, researchers who propose to contact individuals for additional biological materials or information shall, prior to contact, seek REB approval of the plan for making contact.

Application  In certain cases, a research goal may be achieved only through follow-up contact with individuals to collect additional biological materials or information. Under Article 12.3, the REB may have approved secondary use without the requirement to seek consent based, in part, on the impossibility or impracticability of seeking consent from all individuals whose biological materials are proposed for use in research. Where contact with a sub-group is feasible,researchers may subsequently wish to attempt to make contact with some individuals to obtain additional information or biological materials. Contact with individuals whose previously collected biological materials have been approved for secondary use in research raises privacy concerns. Individuals might not want to be contacted by researchers or might be upset that identifiable biological materials were disclosed to researchers without their consent. The potential benefits of follow-up contact must clearly outweigh the risks to individuals of follow-up contact, and the REB must be satisfied that the proposed manner of follow-up contact minimizes risks to individuals. The proposed plan should explain who will contact individuals to invite their participation in the research (e.g., a representative of the organization that holds the individual’s biological materials) and the nature of their relationship with those individuals. Researchers must also ensure that a plan for follow-up contact complies with applicable privacy legislation; for example, some privacy laws prohibit researchers from contacting individuals unless the custodian of the information has first obtained individuals’ consent to be contacted. Whenever possible, it is preferable that re-contact with participants be carried out by the organization or the custodian holding the biological materials. Researchers will need to seek consent from individual participants for any new collection of data or biological materials. Article 3.1 provides further guidance on consent and approaches to recruitment.

D. Storage and Banking of Human Biological Materials

The collection and retention of human biological materials in biobanks creates an ongoing resource for research. Biobanks vary widely in their characteristics: some are very small, while others hold biological materials from thousands of individuals;they may be disease-specific or contain materials from a wide population base. Different types of human biological materials may be stored in biobanks, such as blood, tumour or tissue samples. Biobanks may include, or be linked with, databases of identifiable or non-identifiable information. Materials held in a biobank may be intended only for use in a specific project, or a biobank may be established to provide access to biological materials for numerous projects over many years. Researchers engaged in multi-site research may seek access to materials held in biobanks in different jurisdictions (see Chapter 8 for additional guidance).

Biobanking facilitates research with human biological materials and offers potential benefits to society. Access to stored human biological materials – and associated information about individuals whose materials are banked – can be particularly useful in helping researchers understand diseases that result from complex interactions between our genetic makeup, environmental exposure and lifestyles. Banking of human biological materials may also present risks to individuals whose biological materials and other personal information are stored, accessed, used, retained and disclosed through a biobank. Research involving such materials may also implicate the interests of biological relatives and others with shared genetic characteristics.

Article 12.5  Institutions and researchers that maintain biobanks:

(a) shall ensure that they have or use appropriate facilities, equipment, policies and procedures to store human biological materials safely, and in accordance with applicable standards; and

(b) shall establish appropriate physical, administrative and technical safeguards to protect human biological materials and any information about participants from unauthorized handling.

Application   Safe storage of human biological materials is important to maintain their scientific value, and to protect materials and associated information about participants. Procedures for storage and record keeping shall include effective measures to ensure that participants’ identities are protected. Such measures include the security of facilities and effective procedures for data handling, record keeping and regulating access to human biological materials and information. Appropriate governance of biobanks is also important for managing access to and use of stored biological materials.The appropriate governance structure and management of a biobank will vary depending on its size and usage.

Organizations that maintain biobanks may have their own policies on privacy of, confidentiality of and access to materials. Researchers should be aware of requirements for compliance with such policies. For example, researchers may be required to apply to the organization for permission to access biological samples, and they may be required to enter into an agreement with the organization that sets out conditions for research access and use of materials in the biobank.

Identifiable data derived from human biological materials may be linked to other research or public databases. Such data linking can be a powerful research tool and a valuable resource for monitoring the health of populations, understanding factors influencing disease, and evaluating health services and interventions. However, data linkage also raises separate privacy issues, discussed in Section E of Chapter 5.

E. Research Involving Materials Related to Human Reproduction

Researchers who conduct research involving human biological materials related to human reproduction shall follow applicable guidance expressed in other chapters of this Policy. This section provides further guidance for research involving embryos, fetuses, fetal tissue, and reproductive materials. For the purposes of this Policy the following definitions apply:3

  • Embryo means a human organism during the first 56 days of its development following fertilization or creation, excluding any time during which its development has been suspended, and includes any cell derived from such an organism that is used for the purpose of creating a human being.
  • Fetus means a human organism during the period of its development beginning on the 57th day following fertilization or creation, excluding any time during which its development has been suspended, and ending at birth.
  • Fetal tissue includes membranes, placenta, umbilical cord, amniotic fluid and other tissue that contains genetic information about the fetus.
  • Human reproductive materials means a sperm, ovum or other human cell, or a human gene, and includes a part of any of them.

While research involving materials related to human reproduction has great promise for assisting the development of healthy pregnancies, curing illness, and repairing or rebuilding tissue, it raises special ethical considerations. Accordingly, this research has provoked vigorous debate. Discussion and reflection should continue as our scientific understanding develops.

Significant ethical issues include consent to research involving materials related to human reproduction, privacy concerns, the risk of harm to those who provide reproductive materials, an embryo or fetus, and potential commodification of reproductive capabilities and materials related to reproduction. Researchers and REBs have a continuing duty to remain mindful of the public interest in these issues, and to respect policy, legal and regulatory requirements. In particular, researchers and REBs shall be aware of the detailed requirements and prohibitions set out in the Assisted Human Reproduction Act.

Article 12.6  In addition to requirements in this chapter that apply to all research involving human biological materials, the following guidelines apply to research involving materials related to human reproduction:

(a) Research using materials related to human reproduction in the context of an anticipated or ongoing pregnancy shall not be undertaken if the knowledge sought can reasonably be obtained by alternative methods.

(b) Materials related to human reproduction for research use shall not be obtained through commercial transaction, including exchange for services.

Application  Because of the risk of harm to the woman or the fetus, Article 12.6(a) requires that the use of these materials be avoided where pregnancy is anticipated or ongoing, if research goals may be accomplished in some other way.

Article 12.6(b) reflects concerns about the commercialization or commodification of human reproduction. Exchange for services refers, for instance, to trading a service, such as a medical treatment, for an in vitro embryo or gamete.

Research Involving Human Embryos

Article 12.7  Research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if:

(a) the research is intended to benefit the embryo;

(b) research interventions will not compromise the care of the woman, or the subsequent fetus;

(c) researchers closely monitor the safety and comfort of the woman and the safety of the embryo; and

(d) consent was provided by the gamete donors.

Application  Research potentially altering the embryo by chemical or physical manipulation shall be distinguished from research directed at ensuring normal fetal development. For example, the evaluation of potential teratogens and their effects on certain cell lineages may use early embryos, but those embryos must not be implanted for an ongoing pregnancy.

The Assisted Human Reproduction Act prohibits the creation of a human embryo specifically for research purposes, with the limited exception of creating an embryo for the purpose of improving, or providing instruction in,assisted reproduction procedures.

Article 12.8  Research involving embryos that have been created for reproductive or other purposes permitted under the Assisted Human Reproduction Act, but are no longer required for these purposes, may be ethically acceptable if:

(a)  the ova and sperm from which they are formed were obtained in accordance with Article 12.7;

(b)  consent was provided by the gamete donors;

(c)  embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy; and

(d)  research involving embryos will take place only during the first 14 days after their formation by combination of the gametes, excluding any time during which embryonic development has been suspended.

Application  Research on embryos requires the consent of the gamete donors. The REB may not waive the requirement for such consent. In particular, researchers and REBs should be aware of the Assisted Human Reproduction (Section 8 Consent) Regulations under the Assisted Human Reproduction Act.4

Research Involving Fetuses and Fetal Tissue

Article 12.9  Research involving a fetus or fetal tissue:

(a) requires the consent of the woman; and

(b) should not compromise the woman’s ability to decide whether to continue her pregnancy.

Application  Research may be undertaken on methods to treat, in utero, a fetus with genetic or congenital disorders. Because the fetus and the woman cannot be treated separately, any intervention to one involves an intervention to the other. Research involving a fetus or fetal tissue shall be guided by respect for the woman’s autonomy and physical integrity. Guidance provided in other chapters of this Policy (e.g., consent, privacy and confidentiality, inclusion and exclusion) will also apply. Researchers should ensure that a clear distinction is made between consent to research and consent for any clinical procedures or testing. In practice, this may mean separate consent information and documents, but regardless of the process employed, the differences between research and clinical procedures must be clearly explained.

F. Research Involving Pluripotent Stem Cells

Article 12.10 Researchers who intend to conduct research to derive or use pluripotent stem cells shall follow the Guidelines for Human Pluripotent Stem Cell Research,5 as amended from time to time and published by the Canadian Institutes of Health Research.

Application  The Guidelines for Human Pluripotent Stem Cell Research establish principles that guide the conduct of research with human pluripotent stem cells. The Guidelines explain their scope of application, provide examples of types of research to which they apply, and identify examples of research that conform and do not conform with the guidance. Consent, privacy and confidentiality are addressed, along with issues of commercial interests.

Hybrids and Chimeras

Research involving the creation of animal-human hybrids and chimeras may raise serious ethical concerns, and federal legislation prohibits certain activities relating to their creation. Researchers and REBs are referred to the Assisted Human Reproduction Act and The Updated Guidelines for Human Pluripotent Stem Cell Research for these prohibitions.

Endnotes

[1] See also Canadian Institutes of Health Research, CIHR Guidelines for Health Research Involving Aboriginal People. www.cihr-irsc.gc.ca/e/29134.html [Back]

[2] For discussion of factors relevant to assessing impracticability of consent, see, for example, Canadian Institutes of Health Research, CIHR Best Practices for Protecting Privacy in Health Research, Section 3.3, Secondary Use(September 2005). www.cihr-irsc.gc.ca/e/29072.html#Element3 [Back]

[3] The definitions of embryo, fetus and human reproductive materials are taken from the Assisted Human Reproduction Act (2004, c. 2). http://laws.justice.gc.ca/en/A-13.4 [Back]

[4] Assisted Human Reproduction (Section 8 Consent) Regulations (SOR/2007-137). http://laws.justice.gc.ca/en/SOR-2007-137 [Back]

[5] Canadian Institutes of Health Research, Guidelines for Human Pluripotent Stem Cell Research. June 30, 2010. www.cihr-irsc.gc.ca/e/42071.html[Back]

References

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