Collection of Biological Material for Research
Informed Consent for Collection of Biological Material for Research
Previously Collected Biological Materials
Storage of Biological Materials for Research
Ethical Issues for the REB to Consider
ICF for Genetic Research
Related issues that have been raised frequently at REB meetings
This guideline has been developed by the Bannatyne Campus Research Ethics Boards to address ethical issues pertaining to the collection, storage and use of human biological materials for research purposes. It is intended to aid researchers and Research Ethics Boards (REBs) in the application of principles outlined in sections 8 and 10 of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (August 1998).
Definitions The following are definitions for terms commonly used in the context of research involving stored biological materials:
- Anonymized samples: Samples that have been permanently stripped of identifiers. Also known as 'unlinked' samples. This does not include samples that have been stripped of identifiers for the purposes of one or more investigators.
- Anonymous samples: Samples that are anonymous due either to the absence of tags and records or the passage of time (e.g. biological material recovered from archeological sites). Also known as 'unidentified' samples.
- Biological Materials: Human tissue (e.g. bone, muscle, skin, connective tissue, organ tissue), hair, blood, body fluids, feces, DNA etc.
- Banking: Storage of biological material for future research.
- Genetic Research: The study of genetic factors responsible for human traits. This includes research that involves the identification of genes that make up the human genome; the functions of genes; and the characterization of normal and disease conditions in individuals, biological relatives, families and groups. (TCPS, p. 8.1).
- Identifiable sample: Samples that can be linked to a specific individual (e.g. by way of an identifying tag, patient number or database). Also known as 'linked', 'coded', or 'traceable' samples.
- Stored Biological Materials: Biological materials stored for future research.
- Subject: The term 'subject' is used to refer to the donor of the biological sample, to be consistent with the Tri-Council Policy Statement. Also referred to as the 'participant'.
- TCPS: Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (August 1998).
The collection, storage, and use of human biological materials for research must be undertaken with the free and informed consent of competent donors. In the case of incompetent donors, free and informed consent must be obtained from an authorized third party. In the case of deceased donors, free and informed consent must have been expressed in a prior directive or free and informed consent must be obtained from an authorized third party. (TCPS, Article 10.1).
Informed consent is required when the biological material to be used in research was acquired incidentally to therapeutic interventions (TCPS, p. 10.3). "Acquired incidentally" refers to material left over from clinical samples or extra samples acquired at the same time as clinical samples. The consent form for research use of human biological samples should be separate from the consent form for clinical procedures.
The general principles for informed consent, as outlined in the consent form templates for the Bannatyne Campus, should be applied in addition to the following issues specific to the collection of biological material:
- The purpose of the research for which biological samples are being collected (TCPS, Article 10.2).
- The type and amount of the biological sample to be taken; the manner in which sample will be taken; and the safety and invasiveness of acquisition (TCPS, Article 10.2);
- The potential uses for the sample, including any commercial uses (TCPS, Article 10.2); Use for genetic research must be specified. Note: Generalized descriptions of the potential uses are only acceptable if the samples are anonymized.
- Potential benefits and harms from the research (including, where appropriate, benefits and harms to families, groups, or communities).
- Specify how long the samples will be stored (TCPS, Article 10.2). Note: Storage for an indefinite period of time is only acceptable if the samples are anonymized.
- Specify where the tissue will be stored; and, if applicable, who will be responsible for distributing the tissue for future research.
- The consent form may be designed with yes/no check-boxes giving subjects the opportunity to consent to or refuse certain categories of research. Examples include:
- Future use of identifiable samples for any study relating to the condition for which the sample was originally collected;
- Future use of anonymized samples for any study relating to the condition for which the sample was originally collected;
- Future use of anonymized samples for studies that are unrelated to the condition for which the sample was originally collected;
- Use of samples for one particular study;
- Future contact permitted to ask for permission to do further studies; etc.
- Describe the safeguards to protect the individual's privacy and confidentiality.
- Describe any identifying information attached to specific samples, links to personal information, and potential for traceability (TCPS, Article 10.2).
- When the consent is obtained in a clinical setting, it should be clear that refusal to consent to the research use of biological materials will in no way affect the quality of the patients' clinical care.
- The subject should be told whether they will be provided with the results of the tests. In the case of anonymized samples, where appropriate, subjects may be given the overall results of the study. The results should be disclosed when they signify a clinical problem and methods to ameliorate or treat the condition are available. If the results will not be disclosed, reasons for this should be provided.
- Where the samples are identifiable, the subjects should be able to request that his/her sample be destroyed. The exercise of the right to withdrawal is not possible in the case of anonymized samples and the subject should be informed of this in the consent form.
- Where appropriate, the researcher should inform the subject at the time of consent that the subject is not entitled to any financial or commercial benefits arising from the research.
- If the biological samples or data derived from the research are to be sent to other researchers or institutions, the subject should be informed at the time of consent to participation and given the opportunity to decline (e.g. using a yes/no check box). The recipient researcher's/institution's policies governing storage and access to stored samples should be forwarded to the REB along with the request for approval.
- Research involving the use of previously collected biological samples (i.e. samples that were either collected for another research project or samples from pathological examinations) must be submitted to a REB for review and approval.
- When identification is possible, researchers shall seek to obtain free and informed consent from the donors, or from their authorized third parties, for the use of previously collected biological material (TCPS, Article 10.3). If obtaining informed consent is not feasible, permission must be sought from the REB prior to use of the samples.
- If informed consent was previously obtained (i.e. at time of sample collection), a copy of the consent form must be forwarded to the REB with the new submission. For identifiable samples, the REB will review the original consent forms to determine whether the subjects agreed to participate in the type of research proposed. If the consent forms are inadequate, the researcher must either obtain consent from the subjects for the current research or, if appropriate, anonymize the samples.
- When biological material has been provided by persons who are not individually identifiable (anonymous and anonymized biological material), and when there are no potential harms to them, there is no need to seek the donor's permission to use their biological material for research purposes (TCPS, Article 10.3).
- The principal investigator or appropriate delegate should control access to stored biological material. The principal investigator should outline plans for the transfer of responsibilities regarding the samples and research data, in the event of his/her departure from the institution, prolonged absence or death.
- The study protocol must describe the storage procedures in detail (i.e. where will the samples be stored; how will they be stored to protect the subjects' privacy and confidentiality; who will have access to identifiable information etc.).
- When transferring genetic material and information between researchers, only coded or anonymized information should be transmitted.
- Rendering samples anonymous has the advantage of increasing confidentiality, however, it has the disadvantage of making it impossible to offer potential benefits of the research to donors and their families. This is important when research may disclose previously undiagnosed conditions, such as an inherited predisposition to breast cancer (TCPS, p. 10.2).
- In addition to the privacy and confidentiality of the individual donors, the REBs should take into account implications of the research to biological relatives of the donors or related communities. When harms to the individual or associated groups can be anticipated, investigators should, to the extent possible, plan their research so as to minimize such harms and should consult, when appropriate, representatives of the relevant groups regarding the study design.
In addition to the guidelines for research involving stored biological material, the following must be considered for genetic research:
- The researcher must ensure that the results of genetic testing and genetic counseling records are protected from access by third parties (e.g. insurers, employers), unless free and informed consent to do so is given by the subject (TCPS, Article 8.2). For example, for some studies the REB may request that there be no mention of the study in the subject's medical charts.
- Family information in databanks must be coded so as to remove the possibility of identification of subjects within the bank (TCPS, Article 8.2).
- Children may be at particular risk for stigmatization both within and beyond the family because of knowledge gained through genetic studies. Genetic research involving children [regarding specific diseases] should not be done unless an effective intervention is available and the information to be gained outweighs the risk of harm. (e.g. it may be appropriate to offer testing to children in a family for an early onset condition such as polyposis coli, for which the knowledge affects treatment options, but inappropriate to test children for an adult onset condition such as Huntington Disease for which no effective prevention yet exists (TCPS, p. 8.4).
- Where appropriate, researchers and the REB shall ensure that the research protocol makes provision for access to genetic counseling for the subjects (TCPS, Article 8.4).
- Gene alteration (including "gene therapy") that involves human germline cells or human embryos is not ethically acceptable. Gene alteration for therapeutic purposes and involving human somatic cells may be considered for approval (TCPS, Article 8.5).
In following additional requirements for informed consent should be addressed for genetic research:
- Discuss potential harms (to the subject, family, group or community) that may result from the genetic research. For example, receiving information regarding susceptibility to genetic disease or identification of blood relationships may cause distress to the subject. Describe how such harms will be dealt with as part of the research project (e.g. genetic counseling, TCPS article 8.4).
- Plans for disclosure of the results of genetic research (to the subject and to family members) must be addressed in the protocol and in the consent forms.
- With the exception of the cases provided by law, no genetic information should be transmitted to insurers, employers, educational institutions and other public institutions without express consent from the subject.
- Can the current guidelines (for example with respect to length of storage, or informed consent) be applied to research involving samples that were collected prior to the existence of these guidelines?
Yes, the currently guidelines may be applied. The REBs will address such studies on a case by case basis.
- Do researchers need to specify length of storage for research that does not involve genetic analysis? If not, what is the justification for specifying length of storage for genetic research (other than the fact that it is asked for in the TCPS)?
- Regardless of the type of sample, genetic or otherwise, length of storage should be specified if the samples are not anonymized. While there is no 'upper limit' for the length of storage, the length must be justified. In certain circumstances it may be necessary to maintain the link to the subject, for example if the results of the research may be beneficial to the subject.
- If the samples are anonymized, storage for an indefinite period of time is acceptable.
- The consent form should specify the length of storage and whether the samples are anonymized.
- Should 'minimal risk' research involving human biological materials qualify for expedited review? For example, some research involving anonymous or anonymized tissue may qualify for expedited review.
'Minimal Risk' research may qualify for expedited review. This is to be determined by the chair of the appropriate REB on a case by case basis.
- Would the REB accept consent forms that refer to future use of the samples in general terms, rather than specifying, at the very least, the category of future research (e.g. "research about cardiovascular disease")?
Such consent forms are only acceptable when the samples are anonymous. If the samples are not anonymous, the consent forms need to be more specific with respect to the type of research.
- How should our local researchers address ethical concerns with regard to storage and access when other parties (e.g. the sponsor) are banking the samples?
The consent form should detail who has access and under what circumstances. The recipient researcher's/institution's policies governing storage and access to stored samples should be forwarded to the REB along with the request for approval.