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Revised Draft 2nd Edition of the TCPS (December 2009)

Chapter 12

HUMAN BIOLOGICAL MATERIALS AND MATERIALS RELATED TO HUMAN REPRODUCTION

The use of materials originating from human bodies for research contributes greatly to the advancement of biomedical science. The sources of these materials could be from patients following diagnostic or therapeutic procedures, autopsy specimens, donations of organs or tissue from living or dead humans, body wastes 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 such research centre on acceptable access to and use of biological 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, known values, beliefs and attitudes of those from whom materials originated.

Sections A to D of this chapter provide guidance on research involving human biological materials. 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 materials related to human reproduction.

As noted in Chapter 2, an individual whose data and/or biological materials are used in research becomes a research participant. In regard to human biological materials, individuals may become research participants by agreeing to provide a blood sample for use in a particular study. Individuals may also choose to donate organs, tissue or their entire body for research that occurs after their death. In this way, they become research 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

As described in Chapter 5, information may be categorized along a spectrum of identifiability. Similarly, human biological materials vary in the extent to which they are identifiable. Researchers and REBs must consider if human biological materials proposed for use in research are identifiable or non-identifiable.

Human biological materials are identifiable if they, alone or when combined with other information available to the person who receives the materials and/or information, can reasonably be expected to identify an individual.

The following categories, similar to those found in Chapter 5 in regard to information, help explain the spectrum of identifiability for the purposes of this Policy.

  • Identified human biological materials – identified human biological 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.
  • De-identified/coded human biological materials – direct identifiers are removed from human biological 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 who has the key that links the code with a specific individual can re-link the biological material to the individual).
  • Anonymized human biological materials – human biological materials are irrevocably stripped of identifiers and a code is not kept to allow future re-linkage.
  • Anonymous human biological materials – human biological materials that did not have identifiers attached to them at the time of collection.

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 testing 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 and 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 require use of identifiable human biological materials, especially 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. These are described in Section C below.

Article 12.1 Research involving collection and use of human biological materials requires ethics review by an REB, and:

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

(b) in the case of a participant who lacks capacity, consent shall be given by an authorized third party who should take into account any research directive that applies to the participant; or

(c) in the case of a deceased participant, consent may be given 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 collection and use of human biological materials. During the consent process, a clear distinction should be made between consent to research 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 should be observed.

Where a participant expressed preferences for future research participation in a research directive before losing capacity, researchers and authorized third parties should 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 provide a legal framework for 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 set out in Article 3.2 as well as the following details:

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

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

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

(d) measures 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) anticipated linkage of biological materials with information about the participant; and

(g) the researchers’ plan for handling research 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 biologicalmaterials, 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. The process for requesting withdrawal of biological materials from research should 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 study. For instance, where a participant requests withdrawal of biological materials, information already derived from the materials and aggregated into research findings cannot be withdrawn. Anonymization of biological materials may also preclude subsequent withdrawal. Chapter 3 providesfurther 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 study. Secondary use avoids duplication in primary collection and therefore reduces burdens and costs for participants and researchers. 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 seek a waiver of consent for secondary use of identifiable human biological materials in research shall satisfy the REB that:

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

(b) the waiver 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 biological materials;

(d) the researchers will comply with any known preferences previously expressed by individuals about uses 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 (e.g. legal) permission for secondary use of biological materials for research purposes.

If a researcher satisfies 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. However, consent must be sought where researchers propose to use identifiable human biological materials, unless the researcher satisfies all the requirements in Article 12.3.

The waiver of consent in this article is specific to secondary use of human biological materials. The terms of Article 3.7 addresses alteration and waiver of consent in other circumstances and does 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 Article 9.20.1

Impracticable refers to undue hardship or onerousness such that the conduct of the research is jeopardized; it does not mean mere inconvenience. 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. In some jurisdictions, privacy laws may preclude researchers from using personal information to contact individuals to seek their consent for secondary use of information.2

At the time of initial collection, individuals may have had an opportunity to express preferences about future uses of biological materials, including research uses. For example, individuals may have made an express donation of biological materials for research in accordance with human tissue gift legislation, or may have expressed objection to future use. Researchers and REBs shall respect any known preferences.

An REB may require that researchers engage in discussion with representatives of individuals or groups from whom the biological materials were collected where the proposed research involves greater sensitivity (e.g. research involving stigmatizing conditions). Discussion is not intended 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 research findings. Discussion may also be useful to determine that the research will not adversely affect the welfare of individuals from whom the biological materials were collected. Researchers should advise the REB of outcomes of such discussion and the REB may require modifications to the research proposal based on the feedback.

Article 12.4 When secondary use of identifiable human biological materials without 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 consent based, in part, on the impossibility or impracticability of seeking consent. 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 research 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 for 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 will need to seek consent from these individuals for any new collection of biological materials or information. Article 3.1 provides further guidance on consent and approaches to recruitment.

D. Storage and Banking of Human Biological Materials

Collection and retention of human biological materials in banks, or “biobanks,” creates an increasingly important resource for research. Biobanks vary widely in their characteristics. Some are very small and 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 study or a biobank may be established to provide access to biological materials for numerous studies over many years. Researchers engaged in multi-centre research may seek access to materials held in biobanks in different jurisdictions; Chapter 8 provides additional guidance for such research.

Biobanking offers potential benefits by establishing sources of human biological materials to facilitate research. 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 exposures 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 materialsand 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 uses.

Organizations that maintain biobanks may have their own policies on privacy, confidentiality 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 valuable resource for monitoring the health of populations, understanding factors influencing disease, and evaluating health services and interventions. Data linkage raises separate privacy issues, discussed in Section E of Chapter 5.

E. Research Involving Materials Related to Human Reproduction

This section sets out ethics guidelines relating to research involving human embryos, fetuses, fetal tissue, reproductive materials and stem cells. 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.

Research Involving Human Reproductive Materials

While research involving human reproductive materials 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 reproductive materials, privacy concerns, the potential for harm to those who provide reproductive materials, an embryo or fetus, and potential commodification of human reproductive materials and reproductive labour. 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 should be aware of the detailed requirements and prohibitions found 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 human reproductive materials.

(a) Research using reproductive materials 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) Reproductive materials shall not be obtained, for research use, through commercial transaction, including exchange for services.

Application Because of the potential for harm to the woman or the fetus, Article 12.6(a) requires that the use of such reproductive 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. The purchase or sale, directly or indirectly, of any gamete, in vitro embryo or other reproductive material for the purpose of creating a human being, is ethically unacceptable.

Research Involving Human Embryos

Article 12.7 Research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if intended to benefit the embryo or to advance knowledge if:

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

(b) researchers closely monitor the safety and comfort of the woman and the safety of the embryo.

Application Research potentially altering the embryo by chemical or physical manipulation should 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 assisted reproduction procedures.

Article 12.8 Research involving embryos that have been created for reproductive purposes, but are no longer required for this purpose, may be ethically acceptable if:

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

(b)where the embryo was created using donor gametes, free and informed 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 takes place only during the first 14 days after their formation by combination of the gametes.

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 Consent Regulation under the Assisted Human Reproduction Act.4

Research Involving Fetuses and Fetal Tissue

Article 12.9 Research involving a human 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 should be guided by respect for the woman’s autonomy and physical integrity. Research methods on the treatment of fetuses in utero pose no issues that are not addressed elsewhere in this Policy. 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 in any event, the different uses must be clearly explained.

Pluripotent Stem Cell Research

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 Research5, as amended from time to time.

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 for these prohibitions. This legislation provides the following definitions.

Hybrid means:

  • a human ovum that has been fertilized by a sperm of a non-human life form;
  • an ovum of a non-human life form that has been fertilized by a human sperm;
  • a human ovum into which the nucleus of a cell of a non-human life form has been introduced;
  • an ovum of a non-human life form into which the nucleus of a human cell has been introduced; or
  • a human ovum or an ovum of a non-human life form that otherwise contains haploid sets of chromosomes from both a human being and a non-human life form.

Chimera means:

  • an embryo into which a cell of any non-human life form has been introduced; or
  • an embryo that consists of cells of more than one embryo, fetus or human being.

Endnotes

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

2. For discussion of factors relevant to assessing impracticability of consent, see, for example, the Canadian Institutes of Health Research Best Practices for Protecting Privacy in Health Research (September 2005), Section 3.3 “Secondary Use,” pp. 39 and 40.

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

4. Assisted Human Reproduction (Section 8 Consent) Regulations (SOR 2007-137), www.laws.justice.gc.ca/en/SOR-2007-137/FullText.html

5. The Guidelines for Human Pluripotent Stem Cell Research, www.cihr-irsc.gc.ca/e/34460.html

References