UBC Clinical Research Ethics General Guidance Notes

All Principal Investigators must have a faculty appointment at UBC or if permitted by the applicable board, a staff appointment at an affiliated institution. Principal Investigators bear the overall responsibility for the conduct of the study, including the activities of co-investigators and others on the study team. As the individual responsible for the implementation of the research, the principal investigator bears direct responsibility for ensuring the protection of every research participant. All Principal Investigators are required to meet the responsibilities assigned to them in UBC Policy #LR9, Procedures. These responsibilities include, but are not limited to:

• Bring to the attention of the Head of his/her department any research or other study proposed by him or her, or proposed by a student working under his or her direction, that could be defined as a study involving human participants.
• Present sufficient information to the Head to enable a judgment to be made by him or her as to whether the project comes within the definition of research involving human participants.
• Submit Research for REB review in the form and with the content specified in the UBC Human Ethics Application
• Include as part of each REB application a process for continuing review appropriate to the project.
• Promptly inform the REB that is considering, or will consider, an application by the researcher for any similar or equivalent proposal to:
  • other REBs;
  • funding agencies or regulatory bodies; or
  • research ethics boards, or the like, of other institutions.
• Maintain any issued Certificate of Approval in good standing during the research project.
• Promptly notify the REB that issued a Certificate of Approval of any change in the research involving human participants as proposed and when the project concludes.
• Ensure that informed consent, when required, is obtained from research participants prior to their enrolment into the research project in a form and manner prescribed by TCPS2, UBC Ethical Directives and other relevant national and international standards or condition of funding, where applicable.
• Report all serious and unexpected study related events to the applicable REB in accordance with applicable regulations and guidelines.
• Ensure that any amendments to the study personnel, funding, protocol, consent form or any recruitment procedures are approved by the applicable REB prior to implementation, except where necessary to eliminate apparent immediate hazards to human participants.
• Promptly notify the applicable REB of any unexpected incident, experience or outcome, or any new research knowledge that could impact the conduct of the study or alter the REB's approval or favourable opinion to continue the study.

Investigators conducting clinical trials for either drugs/radiopharmaceuticals, devices or natural health products used for therapeutic purposes have special obligations that are defined in the Food and Drugs Act Regulations that govern each type of experimental therapy. If the study is investigator-initiated, the Investigator bears additional regulatory responsibilities as a study Sponsor. Application Guidance Note #7.11 outlines REB requirements pertaining to regulatory approvals and registration of clinical trials. Investigators conducting clinical trials must also ensure that they comply with the provisions of the TCPS 2 (2018) and the International Conference on Clinical Trials Good Clinical Practice: Consolidated Guidelines.

Investigators (and their institutions) that receive funding or support for studies from the U.S. Federal Government or its agencies are subject to the requirements of the Department of Health and Human Services, found at 45CFR46 (for a list of the applicable agencies click here).

Investigators (and their institutions) that conduct studies that are regulated by the U.S. Food and Drug Administration (including but not limited to most privately funded clinical trials) are subject to the requirements of the U.S. Food and Drug Administration, most of which are found at 21CFR50 and 21CFR56.

Investigators conducting studies that are subject to the U.S. regulations are responsible for ensuring that they comply with these additional requirements, and in particular, the requirements for reporting unanticipated problems to the Research Ethics Board and if necessary to the applicable regulatory agency. Click here to link to the DHHS Regulations, 45CFR46. Click here to link to the U.S. Food & Drug Administration Regulations, 21CFR50 and 21CRF56.

All research involving human participants and all other activities that even in part involve such research, regardless of sponsorship, must be reviewed and approved by a UBC-affiliated REB. No intervention or interaction with human participants in research, including the use of their data, tissue, or the initiation of recruitment, may begin until a UBC REB has reviewed and approved the research protocol, consent documents, and recruitment materials and has issued a certificate of approval. Specific determinations as to the definition of "research" or "human participants", and their implications for the jurisdiction of the REB under University of British Columbia policy are determined by the REBs. Determination of exemption from REB review must be based on regulatory and institutional criteria.

Research involving human participants is defined as an undertaking intended to extend knowledge through a disciplined inquiry or systematic investigation that includes the following:

1. Living human participants; and/or
2. Human biological materials, as well as human embryos, fetuses, fetal tissue, reproductive materials and stem cells. This applies to materials derived from living and deceased individuals. TCPS 2 (2018), Article 2.1

Human Participants are those individuals whose data, or responses to the interventions, stimuli or questions by the researcher, are relevant to answering the research question.

Human biological material include tissues, organs, blood, plasma, serum, DNA, RNA, proteins, cells, skin, hair, nail clippings, urine, saliva and other body fluids.

The following are examples of types of research involving human participants:

• administering a drug, taking a blood sample, doing a test or performing a procedure, clinical, therapeutic or otherwise, upon a person, for research rather than treatment;
• asking people for information whether by telephone, letter, e-mail, internet, survey, questionnaire or face to face interview;
• using non-public records that contain identifying information previously gathered about anyone, either directly or indirectly;
• using identifiable information previously gathered about anyone, (e.g., secondary data analysis. See definition of "identifiable");
• observing anyone's responses or behaviour, either directly or indirectly.

All research involving living human participants (faculty, patients, staff, students or members of the community), all research involving tissues, fluids, biological fluids, embryos or fetuses, or cadaveric remains, all research in which access to human participants involves any records maintained by UBC or any of its affiliated Hospitals, and all research involving data collected from human participants which is to be carried out by faculty, staff or students of the University of British Columbia, shall be reviewed and approved in advance by the REB.

Please note that if your study is funded or supported by the U.S. Federal Government or subject to U.S. Food & Drug Administration oversight and regulations, somewhat different definitions apply. Research funded or supported by the U.S. government is any activity that either: 1) meets the HHS definition of "research" and involves "human participants" as defined by the HHS regulations 45CFR46 102(d)(f) or 2) meets the FDA definition of "clinical investigation" and involves "human participants" as defined by the FDA regulation 21CFR50.3(c)(g).

Research situations that are exempt from the REB review include the following. Note that the opinion of the appropriate REB should be sought if there is any doubt about the applicability of any of the below criteria.

4.3.1: REB review is not required for research that relies exclusively on publicly available information that is legally accessible to the public and appropriately protected by law or is publicly accessible and there is no reasonable expectation of privacy. 

See the TCPS2 (2018) Article 2.2 for examples of and additional information pertaining to the concepts of publicly available information, legally accessible information, and reasonable expectation of privacy.

4.3.2: REB review is not required for research involving the observation of people in public places where there is no intervention or interaction on the part of the researcher, the targeted individuals or groups have no reasonable expectation of privacy, and the dissemination of research results would not allow for the identification of individuals. TCPS 2 (2018), Article 2.3

4.3.3: REB review is not required for research that relies exclusively on secondary use of anonymous information or anonymous human biological materials, provided that the results do not generate identifiable information. Refer to  CREB Guidance Notes for Research Involving Human Biological Materials.

Secondary use refers to the use in research of information originally collected for a purpose other than the current research purpose. TCPS 2 (2018), Article 2.4 When this information was collected anonymously, it can be used for research purposes without REB review. (See Guidance Note #5 for a discussion on secondary use of data and biological information where REB review is required). Examples of anonymous secondary use data may include datasets from a QA/QI survey or questionnaire where the participant's identity was never known.

Important Note: In accordance with Article 7 of UBC Policy #LR9 , genetic material shall not be considered anonymous unless a REB determines otherwise.

UBC REBs use a proportionate approach to review research involving human participants. They review applications in accordance with the level of risk that the proposed study poses to the research participants: the lower the level of risk, the lower the level of scrutiny; the higher the level of risk, the higher the level of scrutiny. In accordance with the TCPS 2 (2018), full review by a fully convened REB is the default requirement, unless the REB has determined that the research is of minimal risk and that delegated review by one or more experienced reviewers appointed by the REB is appropriate. UBC REBs have different procedures for delegated review, in accordance with individual Board policies. UBC REBs retain the right to decide to put any application submitted for minimal risk review forward for full board review.

UBC also strives to use a proportionate approach for multi-jurisdictional studies, i.e. research studies that require review and approval by more than one Canadian research ethics board as a result of the requirements of the TCPS 2 (2018), Article 2.1 or due to UBC's institutional policies. UBC is implementing a variety of processes and entering into agreements with other Canadian Institutions in an effort to avoid duplicate ethical reviews of research; in particular, duplication of review by a fully convened UBC REB in circumstances where a research study has previously been reviewed by a fully convened REB at another Canadian institution.

Minimal risk is defined in the TCPS 2 (2018) as follows: if potential participants can reasonably be expected to regard the probability and magnitude of possible harms implied by participation in the research to be no greater than those encountered by the participants in those aspects of their everyday life that relate to the research. UBC currently recognizes the following categories of clinical research as meeting the criteria for minimal risk and being eligible for delegated review.

Note: If a study is funded or supported by the US Federal government or is subject to the US Food and Drug Administration regulations, only studies that meet the U.S. definition of minimal risk and that are listed in the U.S. Federal Register may be considered as qualifying for delegated / expedited review.

The following types of studies may require full board review depending upon board specific policy.

1. Studies whose purpose it is to collect or use tissue/DNA for the purpose of creating a tissue/DNA bank or adding new sources of tissue to a tissue/DNA bank.
2. Studies whose purpose it is to collect or use tissue/DNA for genetic research related to determining susceptibility of acquiring a disease; or studies whose purpose it is to collect or use tissue/DNA for genetic research the results of which could be potentially harmful to participants if disclosed.
3. Studies whose purpose is the derivation of stem cell lines from human somatic tissue, umbilical cord or placenta OR research involving the grafting of stem cell lines into humans.
4. Minimal risk studies where a waiver of consent or alteration of the required elements of informed consent is being requested.
5. Minimal risk studies that will be recruiting vulnerable populations and there may be increased risk.

The following types of studies do not require full board review when a waiver of consent or an alteration of the required elements of informed consent is being requested.

1. Retrospective chart reviews,
2. studies using data obtained from previously banked anonymized tissue that is not linked to other sources of data,
3. Studies using data from provincially regulated databases/registries (e.g Medical Services Plan, BC Centre for Disease Control) or from disease specific registries with data collected from participants who have already consented to its use for the sort of research being done.
4. Prospective chart or medical record reviews where the data has been de-identified through an acceptable privacy guardian program or anonymized (i.e., there is no way to link the data to the participant), and there is no potential harm to the participant.
5. Prospective chart or medical record reviews where members of the research team are not in contact with participants during the data collection and where the researcher has provided an appropriate justification for why contacting the participants to obtain consent would be impracticable.

Important Note: For guidance pertaining to informed consent requirements for Minimal Risk studies please see Guidance Notes 13 and 14.

UBC REBs are guided by the ethical principles regarding all research involving human participants as set forth in the Tri-Council Policy Statement 2 (2018): Ethical Conduct for Research Involving Humans. The TCPS 2 (2018) core principles are based in the underlying value of respect for human dignity and are as follows:

• Respect for Persons
• Concern for Welfare
• Justice (Core Principles).

For a thorough discussion of the TCPS2's core principles, see Chapter 1 of the TCPS2.

In order for a research project to be approved, the REB must find that:

1. The Investigator (and his/her team) has the credentials to conduct the research.
2. There are no conflicts of interest which will compromise the safety or well-being of participants.
3. The research will generate knowledge that could lead to improvements in health or welfare.
4. The methodology must be scientifically sound and capable of answering the research question.
5. Risks to participants are minimized:
   1. By using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, and
   2. Whenever appropriate, by using procedures already being performed on the participants for diagnostic or treatment purposes.
6. Risks to participants are reasonable in relation to anticipated benefits, if any, and the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the REB will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies those participants would receive even if not participating in the research).
7. Selection of participants is equitable. In making this assessment, the REB will take into account the purposes of the research and the setting in which the research will be conducted and will be particularly cognizant of the special problems of research involving vulnerable circumstances, which have historically included children, elderly, prisoners, pregnant women, those with mental health issues, and those with diminished capacity for self-determination. 
8. Recruitment methods which respect the privacy of individual participants must be followed. Except under unusual circumstances, only members of the participant's/patient's healthcare team may approach the participant/patient regarding participation in the study.
9. Informed consent will be sought from each prospective participant or the participant's legally authorized representative, in accordance with and to the extent required by appropriate local, provincial or national guidelines or regulations.
10. Informed consent will be appropriately documented as required by local, provincial and federal regulations.
11. Any waiver or alteration of the informed process will be properly justified and documented.
12. Where appropriate, the research plan makes adequate provision for on-going monitoring of the data collected to ensure the safety of participants.
13. Where appropriate, there is adequate provision to protect the privacy of participants and to maintain the confidentiality of data.
14. When some or all of the participants, such as children, prisoners, elderly, pregnant women, those with mental health issues, and those with diminished capacity for self-determination, are likely to be vulnerable to coercion or undue influence or international sites are used, additional safeguards have been included in the study, and in the REB review process to protect the rights and welfare of these participants.
15. The resources required for successful completion of the study are committed (e.g., funding, space, personnel, etc.).

The REB may make one of the four following determinations as a result of its review of research submitted for initial or continuing review: Approval, Proviso, Deferral, or Disapproval.

Approval (approve the application as submitted, including the consent form):

• When an acceptable risk/benefit ratio exists and the regulatory criteria required for approval are satisfied (including Institutional approvals) and the approval to proceed is not withdrawn by the Vice‐President Research, the Board of Governors, or the President, the research may be approved as submitted,
• For studies reviewed by the Full Board, the approval date is defined according to the date of the Full Board REB meeting review,
• For studies reviewed via delegated review, the approval date is defined according to the date the reviewer confirms approval via RISe and the Certificate of Approval is released,
• Studies will expire within one (1) year of the date in which the study was approved.

Provisos (approval with modifications/clarifications):

• When an acceptable risk/benefit ratio exists, and the regulatory criteria required for approval are satisfied, but the REB members require modification to any aspect of the application or clarification or further information to secure approval, the REB may recommend “Provisos”,
• A written explanation of the conditions and/or modifications is sent to the Researcher by the Chair of the REB through the REB Office Personnel, via the RISe system,
• When the REB recommends “Provisos”, the REB Chair or designee should ensure that the additional information, modifications, or clarifications required are identified at the REB meeting and that the procedures for reviewing the additional information and issuing the approval are clear. The responsibilities for additional review and the decision regarding approval conditions should be delegated to one of the following:
  • The REB Chair alone,
  • The REB Chair and one or more named REB members that were present at the REB meeting or who submitted written comments on the application,
  • A sub‐group of the REB members designated by the REB Chair or designee or by the REB,
  • A designated REB member or members with sufficient knowledge and experience regarding the research and the regulations,
  • Qualified REB Office Personnel following the UBC‐affiliated REB’s
  • Approval Decisions – Delegation to REBA SOP;
• In deciding the procedures to be followed, the REB should consider the significance of the requested additional information or modifications and the expertise necessary to assess it. Where the information or
• modifications are straightforward, it is acceptable to delegate the consideration of that material to the REB Chair or designee alone,
• Where the additional information/modification is technical (e.g., statistical clarifications), the REB Chair or designee should review the information with consideration given to involving other REB members, such as the lead reviewer(s) or relevant expert member(s),
• When the Investigator provides the Research Ethics Board with proof that the conditions have been met and the documents have been amended, (as confirmed by the REB Chair or designee), the Certificate of Approval will be sent to the Researcher,
• If the Researcher’s response is incomplete and does not fully address the matters raised, requests for further information, modifications or clarification should be sent to the Researcher,
• The reviewers may decide upon reviewing the Researcher’s response that the decision should be deferred and that the application and the Researcher’s response materials should be reviewed at a subsequent Full Board meeting (see ‘Deferral’ process below),
• The approval date is defined according to procedures listed under “Approval” above. The expiry date of the REB approval is calculated from this date; however, the Certificate of Approval is not issued until all of the conditions for approval have been met.​​​​​​

Deferral (defer decision‐making on the application and continue the deliberation of the application at a future Full Board meeting):

• The REB may defer a decision on any submitted research application if it does not have sufficient information to arrive at a determination, or if the REB requires extensive revisions to any part of the research,
• The REB will defer its decision to a subsequent Full Board meeting when significant questions are raised during its review of the research and/or when the criteria required for approval have not been met,
• The REB Chair or designee should ensure that all additional information, modifications or clarifications that are required are specifically identified at the Full Board meeting,
• The research and the Researcher’s response materials shall be reviewed at a Full Board meeting,
• Upon consideration of the research along with the response from the Researcher, at the Full Board meeting, the REB should issue its final decision (approved, provisos, deferral or disapproval),
• Researcher responses must be received and reviewed at a Full Board meeting. The approval date is defined according to procedures listed under “Approval” above. The expiry date of the REB approval is calculated from this date; however, the Certificate of Approval is not issued until all of the conditions for approval have been met.

Disapproval:

• The REB may disapprove the research when it fails to meet the ethical standards for approval and where revision is unlikely to enable the REB to reach a positive determination,
• No other UBC REB or Institutional Official may approve a study which has been previously rejected by a UBC REB. 
• Disapproval cannot be decided through the delegated review mechanism. If the recommendation under delegated review is to disapprove the research, a final decision must be made by the REB at a Full Board meeting.
• The REB Chair or designee should ensure that the reasons for the disapproval are identified at the Full Board meeting for communication to the Researcher. 
• If the research is disapproved, the reasons for disapproval will be communicated to the Researcher and the Researcher will be given an opportunity to respond in person or in writing.  
• A researcher may request reconsideration of a decision made by the REB and has the right to appeal the REB’s decision pursuant to the provisions of UBC Policy LR9, as well as SOP 409 “Reconsideration of REB Decisions and Appeal Process”.

In accordance with the TCPS 2 (2018), UBC Policy LR9 and the US Federal Regulations, all research studies must be reviewed by the REB at least annually, if not more frequently. UBC REBs will not issue certificates of approval for terms longer than one year. The determination of what constitutes a one year term varies slightly, depending upon whether or not the study was reviewed by the full board process, by a delegated review process or whether or not it is a renewal of a previously approved study. Full Board Approvals are effective one year from the meeting date at which the application was reviewed and approved. Delegated review approvals are effective one year from the date that the delegated reviewer issued his or her approval of the study and the certificate was issued. Annual renewal approvals will be effective one year from the date of issuing of the certificate of approval, unless the annual renewal was required to be reviewed by the Full Board. If the annual renewal is required to be reviewed and approved in a full board meeting, the one year period will be effective from the date of the meeting in which the renewal application was reviewed and approved.

Please note that approval of study amendments does not affect the expiry date of the original certificate of approval or annual renewal.

UBC's REBs may issue certificates of approval for terms of less than one year. The Board's determinations will be based upon the design of the study in question, and the perceived level of risk to participants.

All of UBC's REBs mandate that a research protocol MUST be submitted for all research applications regardless of the type of study. These must be submitted as separate documents attached to box 9.1 of the RISe application form. Research proposals submitted to granting agencies may be used to meet this requirement. Protocols must include the following components:

1. A background literature review (with accompanying references) that includes an explanation of the need/justification for the study.
2. The study purpose
3. Hypotheses
4. Objectives
5. Specification of endpoints/outcomes (if applicable)
6. Research design including statistical analysis plan (if applicable) and
7. Detailed research procedures

Important Note: The requirement for a research protocol is a UBC-wide REB policy. Your application will be sent back, and approval delayed, if a protocol is not submitted with your application. Ensure that ethical issues as implicated by the research design are addressed within in the protocol.

For all research, UBCs REBs must be satisfied that the value and the scientific validity of the study warrant it being conducted such that study participant's time and effort regardless of level of risk of the study, is not being expended with no corresponding benefit to either society or to the participants.

Minimal Risk Research: Clinical Research that poses no more than minimal risk may not require peer review. The REB must be satisfied about both the value and scientific validity of the study. Research in the humanities and social sciences that poses no more than minimal risk does not normally require peer review. TCPS 2 (2018), Article 2.7

More-than-minimal-risk research:

Peer review is required for all studies above minimal risk.  Peer review (sometimes referred to as scholarly or scientific review) is generally understood by UBC REBs as a review of the importance of the research question (value) and the validity of the methodology. Practices around scholarly review vary between disciplines, fields of research and groups. The primary goal of this requirement is to ensure that above minimal risk research protocols that are submitted for ethical review satisfy the relevant disciplinary standards in terms of both value and scientific validity. It is anticipated that this in turn will facilitate the ethics review process for the REB, reduce the number of provisos and deferrals issued to researchers, and improve the overall success of the research. 

Peer - Scientific Review Template March 17, 2017  must be completed and attached to an application when a protocol:

1. Is above minimal risk; AND
2. Has not undergone internal or external peer review (includes granting agency approval); AND
3. Will be submitted to the UBC CREB.

Note that if your research proposal has received a scientific peer review form from an independent authority in your field of expertise, or from your trainee's supervisory committee, this should be attached to Box 9.8 of the RISe application form.  In these instances, you are not required to also have the CREB Scientific / Peer Review Form document completed.

Independent peer review: Scholarly review by an independent group of experts who are not affiliated with the institutional department conducting the research, or with the company sponsoring the clinical drug/device trial is preferable to peer review by experts who are not independent.

UBC's REBs Requirements: All more than minimal risk studies submitted to UBC REBs require a peer review or scholarly review, or an accepted argument about why one has not been obtained. Your application will be sent back to you, if you do not provide appropriate peer review information on page 4 of the RISe application. If you make an argument that one is not necessary and the REB does not agree, you may be asked to submit one as a condition of study approval.

Depending upon the nature of the study, the REB will require additional documentation to be submitted with the application for its review. Required documentation includes:

• A draft informed consent form (unless waiver of consent is being requested)
• Where applicable, assent forms, tissue consent forms, letters of initial contact recruitment letters or brochures or flyers, telephone scripts, radio or TV ad scripts, and advertisements
• Where applicable all study materials including, questionnaires, interview scripts, patient diaries, patient wallet cards, tests or patient information or instruction pamphlets
• Where applicable, the Investigator's Brochure, proof of appropriate agency authority or regulatory approval such as Health Canada no objection letters, school board approvals, agreements or contracts with aboriginal communities, etc.

(See Application Guidance Notes on Required Regulatory Approvals # 7.8.A and Registration of Clinical Trials Guidance Note # 7.11 )

Note that all additional documentation should be attached as separate documents, (e.g. not in the appendix of the protocol), to the appropriate box on page 9 of the RISe application. The certificate of approval populates from the boxes on page 9 of the application and failure to do this will result in a document not being listed on the certificate of approval (COA).  Box 9.9 does not populate on the COA and theses document are for reference only.

Wallet Cards
The CREB recommends that all participants enrolled in a clinical trial involving drug administration in which they are not continually in a controlled environment (hospital, research clinic, etc.) should be provided with a wallet card describing the basic information about the trial.

An example of such a card could be as follows:
Name of Participant
Name of Study
Participant Study Number (if applicable)
Name of Principal Investigator
Treatment they are receiving (or which they could be receiving if they are in a blinded study)
Contact information of investigator/research staff (not necessarily 24/7)

In accordance with the provisions of the TCPS2's principle of justice, the selection of participants must be equitable. In assessing this aspect of the research proposal, the REB will take into account the purposes of the research and the setting in which the research will be conducted and will be particularly cognizant of the special problems of research involving vulnerable circumstances. Vulnerability is often caused by limited capacity, or limited access to social goods, rights, opportunities and power. Individuals or groups in vulnerable circumstances have historically included children, women, prisoners, those with mental health issues and those with diminished capacity for self-determination. Special consideration will be given to the potential for inclusion of participants in vulnerable circumstances. The research proposal must never intentionally or inadvertently increase or exploit this vulnerability, nor should these types of populations be excluded from research, which is potentially beneficial to them as individuals or to the group that they represent.

Individuals who lack capacity to consent to participate in research shall not be inappropriately excluded from research. However, the inclusion of participants who lack the capacity of consent must meet the requirements of the TCPS2, Article 4.6, which outlines the following criteria:

• the research can be addressed only with participants within the identified group; and
• the research does not expose the participants to more than minimal risk without the prospect of direct benefit for them; or
• where the research entails only minimal risk, it should at least have the prospect of providing benefits to the participants or to a group that is the focus of the research and to which the participants belong.

Important Note: U.S. Federal Regulations differ in their approach to allowing individuals who are legally incompetent to consent to participate in research that is more than minimal risk and not of direct benefit to them. UBC's REBs are governed by the TCPS2 and will not approve such research unless the TCPS2 criteria are met.

Researchers must not exclude individuals from participation in research on the basis of attributes such as culture, language, religion, race, disability, sexual orientation, ethnicity, gender, reproductive capacity, or age unless there is a valid reason for the exclusion, which is explained to the REB in the application. Individuals who are not proficient in the language used by UBC Researchers should not be automatically excluded from the opportunity to participate in the research. Researchers should consider appropriate measures to allow such individuals to participate.

See TCPS2, Chapter 4, Fairness and Equity in Research Participation, for further information on inclusion and exclusion criteria in research.

See Application Guidance Note #5.4 for tips on filling in your application appropriately

As stated in TCPS 2 (2018), Article 3.1 "the approach to recruitment is an important element in assuring voluntariness. In particular, how, when and where participants are approached, and who recruits them are important elements in assuring (or undermining) voluntariness."  It is the researchers' responsibility to demonstrate to the REB that their research methodology adheres to the principle of voluntariness.

All recruitment material used must be approved by the REB in the form it will be used in before recruitment begins, e.g. a newspaper ad and a poster should be submitted separately even if the text is only slightly different. Recruitment materials should give potential participants a basic understanding of the research, what would be expected of them (including time commitment), and their potential eligibility for the study. Include directions for the potential participant to contact the research team, if they believe they are interested in the study. All recruitment material should be labeled with a version date. Do not include any payment or remuneration value for participation on the recruitment material; however, you may mention an honorarium, gift, or small token of appreciation etc. will be given.  See Guidance Note 10.1.3 above.

In some situations, the prospective participant's primary care (i.e. family doctor) physician (or other primary health care provider) holds the participant's personal contact information. In these situations, permission to release the contact information must be obtained from the participant by the primary care physician before the researcher can use the information for recruitment purposes. The primary care physician must either verbally ask the prospective participants' permission to release their names to the Investigator, or distribute an introductory letter describing the study to the prospective participants, with details on how to contact the Investigator if they are interested in participating. Private practice physicians fall under the provisions of the British Columbia Personal Information Act (PIPA). PIPA section 21 regulates the disclosure by physicians of personal information for research or statistical purposes.

The BC Freedom of Information and Protection of Privacy Act (FOIPPA) applies to public sector institutions referred to in the Act as "public bodies". These include some health care (e.g. hospitals and health authorities), public (e.g. government Ministries, WCB), and educational (e.g. School boards, universities) bodies. Special rules apply to Health Ministry databases and to designated health information banks under Part 2, Division 1, Sections 3 and 4 of the E-Health (Personal Health Information Access and Protection of Privacy) Act.

Section 35 of FIOPPA limits the disclosure of personal information collected by such bodies to third party researchers such that this information cannot be released by the public body for contact purposes, unless the research purpose, the use for contact and the manner of contact are approved by the Privacy Commissioner [Section 35(2)].  This limitation does not apply to research conducted or sponsored by the public body, itself (see Article 11.5 below).

Where the disclosure of contact information under section 35 of FOIPPA is sought by a researcher for recruitment, the privacy officer or, as applicable, the custodian of the relevant database or registry should be consulted to explore the availability of options for recruitment or, if appropriate, for obtaining the Commissioner's approval for disclosure for contact purposes. Even though researchers may have access rights to the records or electronic registries of a public body for clinical or other purposes not related to the research, it is not appropriate for researchers to use such access to identify or obtain contact information about prospective research subjects without proper authority and approvals under FOIPPA.

Researchers should be aware that the REB must also review and approve the plan for initial contact and that it is within the REB's discretion to determine that such contact is not ethically acceptable notwithstanding the Privacy Commissioner's approval. [TCPS2 Article 5.6]

Part 2, Division 3, Section14 of the E-Health Act limits the disclosure of personal information held by a Ministry database or by a designated health information bank. This information cannot be released by the bank or database for the purpose of contacting named individuals unless the request for disclosure has been approved by the Data Stewardship Committee created under the Act, and provided that the research purpose, the use for contact and the manner of contact are approved by the Privacy Commissioner (Part 2, Division 3, Section 14.2.1(c)).

Participants who have previously consented to be included in a registry for research purposes including consented to be contacted for future research studies, must first be contacted by mail using the contact information included in the registry. The contact letter must be approved by the REB and must explain to the prospective participant how their contact information was obtained, in addition to explaining the reason why they are being contacted. See Guidance Notes 10.3.1, for specific inclusions for the letter of initial contact.

Ideally, prospective participants in clinical studies are approached for the purpose of recruitment into a research study by someone who is within their circle of clinical care (see "Circle of Care: Sharing of Information for Health Care Purposes" for further discussion).

Investigators who are not acting as health care providers for prospective participants but who are attached to a hospital department/clinical/medical unit that offers clinical care and conducts research on the patient populations of the specific unit, may be able to obtain prospective participant names from the patient lists of their hospital's medical units in order to determine eligibility for contact provided that the practice is agreed upon by the head of the unit, and the participating physicians. In such circumstances, with REB approval, prospective participants may be contacted in writing with an explanation of how their personal contact information was obtained, and a description of the Investigator's relationship to the medical unit, department or clinic. See Guidance Notes 10.3.1 for specific inclusions for the letter of initial contact.

If the investigator is not directly affiliated with the hospital department/clinical/medical unit then the inclusion/exclusion criteria should be sent to the manager of the patient database or privacy officer for the department with a request that the REB approved letter of initial contact be sent out to prospective participants so that if a patient is interested they can contact the site.

Alternatively, and only with REB approval, clinic staff may approach patients directly to advise them that a study is being conducted and to enquire if the patient would like to find out more information concerning it.  If so, patients may be referred to study staff.

Investigators should be aware that the REB will make the determination concerning the most appropriate method for initial participant contact and approved methods will depend upon the context of the study.  In most instances however, an initial contact letter offering the participant the opportunity to contact study staff if they are interested in a study is preferred as it provides prospective participants the option to contact the investigator or not and avoids the possibility of unsolicited personal approaches. 

The TCPS 2 (2018) states that "the analysis, balance, and distribution of risks and potential benefits are critical to the ethics of research involving humans. The principle of Concern for Welfare imposes an ethical obligation to design, assess and conduct research in a way that protects participants from any unnecessary or avoidable risks. In their review, the REB should be concerned with an assessment that the potential research outcomes and potential benefits merit the risks." TCPS 2 (2018) Chapter 2, Balancing Risk and Potential Benefit

UBC's REBs are responsible for determining whether the research presents an ethically acceptable balance of risks and potential benefits. The decision to participate in approved research, however, is that of the potential participant, based upon his or her own appreciation of whether it serves their interests or welfare to do so. With this in mind, the general description of the research and the research risks and benefits should be disclosed in such a way as to avoid therapeutic misconception. It should be made abundantly clear that the primary purpose of the study is for research and not to produce therapeutic benefits for participants. Participants must clearly understand how a clinical trial design could potentially interfere with the healthcare options that are available to them in order to make an informed decision about participating. See TCPS 2 (2018) Chapter 11, Section A, Therapeutic Misconception

Information on risks in the application and the consent form must be consistent with the information provided in the protocol and the Investigator's Brochure/Product Monograph if applicable. If risk information/data is provided from another source, the source of the data should be identified in the application.

• Minimize Harms: Include an explanation of any strategies put in place to minimize and/or manage the harms for participants and others (e.g. reporting side effects, rescue medication, early withdrawal from the study)
• Unknown Interactions With Other Drugs: Disclose whether the research necessitates that certain medication or treatments not be administered during the study so that potential participants may evaluate this in the context of their current health.
• Wash-Out Periods/ Requirements for Stopping Medication: The consent form must explain the symptom/signs that participants could experience from being taken off any medication, and the potential impact on the participants health.
• Risks to Pregnant Women and Others: Potential harms to individuals other than the participant must be noted (e.g. unborn children, sexual partners, family members). The risk of any harms to pregnant women, to women who could become pregnant during the course of the research, or to men in relation to the reproductive capacity need to be disclosed in the consent form.

Specific instructions concerning the prevention of pregnancy must be included in the consent form as follows:

• Specific measures to take to prevent pregnancy (note: Acceptable measures will vary depending upon the Research Ethics Board)
• How to notify the researcher if a participant suspects that she is pregnant; and
• What would happen if a pregnancy should occur during the research.

• Please note the University of British Columbia’s Clinical Research Ethics Board (CREB) does not require that Pregnancy Consent forms are submitted unless such a case presents.  

  If a participant or partner of the participant becomes pregnant, then a separate consent should be submitted for REB review prior to the collection of pregnancy data.  Please notify the study sponsor.

For further information about standard disclosures around risks and discomforts, see the BC Common Clinical Informed Consent Form Template, section "What are the possible harms and discomforts?".

Note that risks to the participants may also include social harms such as breach of confidentiality, social stigmatization, threats to reputation and psychological harm. Explain what strategies are in place to minimize and/or manage the risks for participants and other affected individuals.

It is the PI's responsibility to ensure that any harms such as psychological distress, arising from any knowledge that participants could obtain as a result of their participation in any type of research study, be eliminated if possible, and if elimination is not possible that such harms be minimized to the greatest extent possible.

In the course of research, there are tests that might have results that impact seriously on the research participant's health or have other serious implications (e.g. HIV, Hepatitis, some genetic tests, etc.) Appropriate pre- and post-test counselling services shall be made available to the participant and when appropriate, to his or her family.

Some studies may provide results to participants which identify them as belonging to a high-risk group on the basis of the result (e.g. genetic status, biochemical test result). TCPS2 Article 13.2 specifies that in the case of research involving individuals, families, and groups in genetic research, the researchers must describe a plan to manage "the types of information that may be revealed through genetics research - and the implications of this information for participants and their biological relatives". TCPS2 Article 13.4 requires that "where researchers plan to share results of genetic research with participants, the research proposal should make genetic counselling available at that time, where appropriate." This will normally require making both pre- and post-testing counselling available. See Article 12.3 above.

In addition, some genetic testing may provide results to participants which identify them as belonging to a high-risk group on the basis of their genetic status. If this may be the case in the context of the specific study, the consent form must include a statement that informs participants that any knowledge gained from the research study that identifies the participants as belonging to a high-risk group, may reduce the ability of the participant to obtain health and/or life insurance.

Due to the possibility of not being able to continue on treatment after a study is completed, the following wording should be included in the consent form. See the BC Common Clinical Informed Consent Form Template, section "After the study is finished":

You may not be able to receive the study treatment after your participation in the study is completed. There are several possible reasons for this, some of which include:

• The treatment may not turn out to be effective or safe.
• The treatment may not be approved for use in Canada.
• Your caregiver may not feel it is the best option for you.
• You may decide it is too expensive and insurance coverage may not be available.
• The treatment, even if approved in Canada, may not be available free of charge.

If the participant received a device, explain if they will keep the device or not (i.e., “The device that was implanted for this study will not be removed, but it will continue to be monitored as part of standard or usual care.”)

UBC REBs require numeric (usually percentage) quantification of risks wherever possible. Quantify the foreseeable risks of harms (side effects) or inconveniences (discomfort to incapacity) to the participant associated with each procedure (including radiation risks from X-rays, therapy, test, interview or other aspect of the study). For specific guidance on X-Rays, please see Guidance Note #17. Quantification should include information about the seriousness and consequences of the different types of adverse events that have been observed, as well as the probability of these events occurring. Quantification of these harms should emphasize the incremental risk with the experimental intervention as compared to placebo or no treatment, wherever possible.

The following information (and any other relevant information) should be included in the consent where applicable:

Explain the risk that the participant’s condition may worsen.

The CIOMS standard frequencies for Risks are outlined as follows:

Very common (10% or greater)

Common (1% - 10%)

Uncommon (0.1% - 1%)

Rare (0.01% - 0.1%)

Very rare (less than 0.01%)

Frequency not known (cannot be estimated from the available data)

• In cases where risks from human research is not readily available (for example, Phase I studies), please provide details of any relevant risks shown in previous studies conducted on animals.
• Disclose all known risks and discomforts associated with study procedures, including social and psychological risks/discomforts, risks to others, reproductive risks, genetic risks, risks that require counselling (describe whether counselling will be made available), and risks related to testing for reportable diseases, and risks related to use of placebo or associated with drug washout periods.
• Indicate whether the harms of the study drug may be severe, disabling, irreversible, or may cause death.
• Indicate whether the risks are fully known and whether there may be unexpected harms/side effects, including unexpected effects of novel drug combinations or because the study drug is in an early stage of development.  Provide previous study results if known.
• Clarify the risks to women should they become pregnant as well as any risks to potential fathers (see recommended wording below);
• Instruct participants that they should immediately inform their study doctor of any side effects they experience, if applicable;
• Instruct prospective participants to discuss the known side effects with their study doctor prior to their decision to participate in the study;
• Clarify that participants assigned to the placebo group may experience worsening of their condition since they will not have their condition treated.
• List in bold text any medications, supplements, or foods that should not be taken while on the study.
• Disclose any potential loss of opportunity to receive standard care or the related known benefits from standard care.
• For studies that involve questionnaires or surveys, include that there may be potential risks of  feeling anxiety / sadness etc. and that the participant does not have to answer any questions that make them feel uncomfortable. 

Unanticipated side effects: The consent form must include an explanation that unanticipated side effects, including severe or irreversible ones, could occur if a novel combination of drugs is being tested, even if the individual drugs are not expected to have these side effects.

Research benefits can be direct, e.g. a health condition improves, or indirect, e.g. the research benefits a group in which the participant belongs. As stated in the TCPS 2 (2018), "researchers should be sensitive to the expectations and opinions of participants regarding potential benefits of the research." (TCPS 2 (2018), Chapter 4, Fairness and Equity in Research Participation ) The consent form and the application should specify the benefits to the prospective participants. If there are no direct benefits to the participants from participating in the research, this must be stated explicitly. If any specific therapeutic benefits cannot be assured, but may be hoped for by the participant, state explicitly that the participant may or may not benefit from participation in the study. For sample wordings around the benefits of participating in a research project, see the BC Common Clinical Informed Consent Form Template, section "What are the potential benefits of participating?".

As stated in the TCPS 2 (2018), Article 3.12, evidence of consent shall be contained either in a signed consent form or in documentation by the researcher of another appropriate means of consent. In most circumstances, the UBC clinical REBs require that informed consent be documented by the use of a written consent form approved by the REB and signed and personally dated by the participant or the participant's legally authorized representative. The investigator should allow the participant or the legally authorized representative adequate opportunity to read the consent document before it is signed and dated. A signed and dated copy of the document must be given to the person signing the form. See UBC REB SOP 701 for further discussion of the documentation of informed consent.

The written informed consent document should be in plain language understandable to the participants of the study, e.g. at a grade 7 level. See the BC Common Clinical Informed Consent Form Template for reference.

Where consent is not documented in a signed consent form, researchers may use a range of consent procedures, including oral consent, study notes and other strategies, for documenting the consent process. Consent may also be demonstrated solely by the actions of the participant (e.g., through the return of a completed questionnaire). Where there are valid reasons for not recording consent in writing, the procedures used to seek consent must be documented and approved by the REB. TCPS 2 (2018), Article 3.12

Exception: For research that is funded or supported by the US federal government, a REB may only waive the requirement for a signed consent form for some or all participants in accordance with applicable US Federal regulations, see UBC REB SOP 701, 4.8.2

The person obtaining consent must be sufficiently familiar with the study, the disease being treated (if applicable), and the process of informed consent. This will usually be the investigator or a designated research assistant. Consent in most cases should be obtained in a face to face discussion with the potential participant and legal representative, if applicable.

For guidance on electronic consenting please see here

When medically relevant to the safety of participants, the investigator should independently document the obtaining of informed consent in the medical record, noting the date, the participant's full understanding of the risks and benefits of enrollment, the voluntary nature of participation, and if required, a copy the consent form. If participation in a clinical research study or if it is the intention or a likely consequence of the research that test results, which might affect treatment decisions or have important implications (e.g. HIV tests, genetic tests), will become part of the participants' health record, this must be disclosed in the consent form.

For studies which are using electronic medical records (EMRs) and will have the consent form as part of the EMR (e.g. Cerner), please include the following required wording.  Please note this wording should also be amended and used accordingly for studies where the hard copy consent form will be placed in the patient’s medical record:

“Because this is a treatment study, your signed consent form will be included in your electronic medical record, and your healthcare team will be alerted that you are on a study. This is to ensure your healthcare team has a little information about the study so that they can treat you safely according to the study protocol.”

The following is standard UBC guidance around specific research situations regarding informed consent. Standard informed consent disclosures can be found in the BC Common Clinical Informed Consent Form Template. If you are unable to find appropriate guidance for your research, contact the applicable Research Ethics Board administration.

UBC's REBs mandate standard required disclosures with respect to the following topics. Refer to the BC Common Clinical Informed Consent Form Template for detailed information and standard wordings.

UBC's REBs have administrative requirements for research consent forms in relation to the following topics. Refer to the BC Common Clinical Informed Consent Form Template for detailed information and standard wordings.

The TCPS2, Article 3.7A, states the REB may approve research without requiring that the researcher obtain the participant's consent where the REB is satisfied, and documents, that all of the following apply:

1. the research involves no more than minimal risk to the participants;
2. the lack of the participant's consent is unlikely to adversely affect the welfare of the participant;
3. it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required;
4. whenever possible and appropriate, after participation, or at a later time during the study, participants will be debriefed and provided with additional pertinent information in accordance with the TCPS 2, Articles 3.2 and 3.4, at which point they will have the opportunity to refuse consent in accordance with the TCPS 2, Article 3.1; and
5. the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions. (TCPS2, Article 3.7.)

It is the responsibility of the researcher to demonstrate that a particular research project fits into the above criteria. This should be done by listing each of the above criteria and an explanation as to why the research fits into it underneath. This may entered into the RISe application Box 6.7A.

There are situations where an individual who requires urgent medical care is unable to provide consent for research due to loss of consciousness or capacity and the delay to seek authorized third party consent could seriously compromise that individual's health. In these cases and subject to all applicable legal and regulatory requirements, research involving medical emergencies may be conducted only if it addresses the emergency needs of the individuals involved, and then only in accordance with criteria established in advance of such research by the REB. NOTE: This section does not apply to publically declared emergencies, e.g. SARS. See TCPS2, Article 3.8 to read more about research conducted during publically declared emergencies. (TCPS2, Article 3.8 (paragraph just above))

As stated in the TCPS2, Article 3.8, the REB may allow research that involves medical emergencies to be carried out without the consent of participants, or of their authorized third party, if all of the following apply:

1. a serious threat to the prospective participant requires immediate intervention;
2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care;
3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant;
4. the prospective participant is unconscious or lacks capacity to understand the risks, methods and purposes of the research project;
5. third party authorization cannot be secured in sufficient time, despite diligent and documented efforts to do so; and
6. no relevant prior directive by the participant is known to exist.

When a previously incapacitated participant regains capacity, or when an authorized third party is found, consent shall be sought promptly for continuation in the project, and for subsequent examinations or tests related to the research project. (Ibid, 3.8.)

Research in emergency medicine must be reviewed by the REB, be restricted to the emergency needs of the participants, and be conducted under criteria designated by the REB. The above outlines the minimal conditions necessary for the REB to authorize a research without free and informed consent.

As stated in Chapter 5, Section D of the TCPS2, secondary use refers to the use in research of information originally collected for a purpose other than the current research purpose. Common examples are social science or health survey datasets that are collected for specific research or statistical purposes, but then re-used to answer other research questions. Information initially collected for program evaluation may be useful for subsequent research. Other examples include health care records, school records, biological specimens, vital statistics registries or unemployment records, all of which are originally created or collected for therapeutic, educational or administrative purposes, but which may be sought later for use in research. (TCPS, Chapter 5, Section D)

Researchers who have not obtained consent from participants for secondary use of identifiable information shall only use such information for these purposes if the REB is satisfied that the following TCPS2 (Article 5.5) requirements are met:

1. identifiable information is essential to the research;
2. the use of identifiable information without the participants' consent is unlikely to adversely affect the welfare of individuals to whom the information relates;
3. the researchers will take appropriate measures to protect the privacy of individuals, and to safeguard the identifiable information;
4. the researchers will comply with any known preferences previously expressed by individuals about any use of their information;
5. it is impossible or impracticable to seek consent from individuals to whom the information relates; and
6. the researchers have obtained any other necessary permission for secondary use of information for research purposes.

The researcher must satisfy all of the above conditions for the REB to approve the research without requiring consent from the individuals to whom the information relates. (TCPS2 5.5) Researchers must ensure that they specifically address each of these requirements in the context of their application for waiver of consent by responding to each article individually.

For the purpose of these Guidance Notes, identifiable information is information that may reasonably be expected to identify an individual, alone or in combination with other available information. All research that involves the secondary use of identifiable information either must seek informed consent or request a waiver of informed consent using the above criteria. All research where the investigators only have access to de-identified information, but a link either does exist or did exist, must still submit for REB review; however, a request for waiver of consent is not required. Only secondary use of anonymous information, where information was collected anonymously, e.g. a link never existed, may qualify to be exempt from REB review as per Article 4.3.

Secondary use of biological material refers to the use in research of any material that was originally collected for a purpose outside of the current research purpose. This involves biospecimens that are already collected and stored such as materials that were collected for an earlier project, biospecimen from an institute's Pathology Department or biospecimen from a certified biobank. Informed consent is required for the secondary use of identifiable human biological material unless the researcher can satisfy the REB that the criteria outlined in TCPS 2 Article 12.3 are met. Note that secondary use of biological materials left over after diagnostic tests is only authorized when there is no further current or future clinical need for those materials and the Pathology Department has released the specimens for research use. See the TCPS 2 (2018) Chapter 12, Section C for further discussion of consent and the secondary use of biological information.

Please note that prospective collection of samples does not fall under the category of secondary use and researchers must satisfy the research consenting requirements by either (1) creating a consent form for the prospective collection or (2) applying for a waiver addressing TCPS2 article 12.3. Please note that consenting prospective participants is required unless the REB has determined that a waiver of consent can be justified.  

Scenario:  A patient undergoing surgery as a part of clinical care has a biospecimen removed.  These samples are then discarded as per clinical SOPs.  Rather than having samples discarded, researchers would like to collect these samples for research.  This researcher is required to submit an ethics application and consent participants for the use of their biospecimens for research.

In situations where a waiver of consent was granted by the REB or when a researcher wants to re-contact a former participant for further information without their explicit consent for re-contact, the researcher must provide the REB with a plan for making contact with the participant. This plan must be approved by the REB before contact is made. The plan should include the following:

1. Demonstrate that the potential benefit of the follow-up contact clearly outweighs the risks to individuals;
2. Explain who will contact and invite the individuals to participate;
3. Describe the nature of the relationship of the above persons to the individuals.

The researchers must ensure that their method of contact complies with applicable privacy laws. The REBs prefer that the contact be made by the custodian of the original data set rather than the researcher. (TCPS 5.6.) The consent form should also explicitly state the process by which the waiver was authorized and indicate a contact who the potential participant can call or email, if they have further questions or concerns.

The following section provides examples where a waiver or alteration to the consent process may be appropriate.

Capacity is the ability of prospective or actual participants to understand relevant information presented (e.g. purpose of the research, foreseeable risks, and potential benefits), and to appreciate the potential consequences of any decision they make based upon this information. (TCPS 2, Chapter 3, C.) The TCPS2 states that a participant may have developing or diminished capacity, i.e. a minor or person with a cognitive impairment, but still be able to decide whether to participate in certain types of research (ibid). If a potential research participant has the capacity to consent, consent must be sought from them before research with them commences. If a person does not have the capacity to consent, they should still be involved in the consent process where possible and appropriate and given the opportunity to assent. If a person who lacks the capacity to consent declines to participate in research, his or her dissent must be respected and the person may not be included in the research, see Article 15.5 for further discussion on assent and dissent.

Capacity to consent to research is not a static determination; it may vary over time, and upon the complexity and circumstances of the decision being made. It is the responsibility of the Principal Investigator (PI) to determine and monitor participants' capacity to consent and to describe this to the REB in the context of the proposed study.

Research involving individuals who lack the capacity, either permanently or temporarily, to decide for themselves whether to participate, must meet at a minimum the following conditions in order to be considered for REB approval:

1. the researcher involves participants who lack the capacity to consent on their own behalf to the greatest extent possible in the decision-making process;
2. the researcher seeks and maintains consent from authorized third parties in accordance with the best interests of the persons concerned;
3. the authorized third party is not the researcher or any other member of the research team;
4. the researcher demonstrates that the research is being carried out for the participant's direct benefit, or for the benefit of other persons in the same category. If the research does not have the potential for direct benefit to the participant but only for the benefit of the other persons in the same category, the researcher shall demonstrate that the research will expose the participant to only a minimal risk and minimal burden, and demonstrate how the participant's welfare will be protected throughout the participation in research; and
5. when authorization for participation was granted by an authorized third party, and a participant acquires or regains capacity during the course of the research, the researcher shall promptly seek the participant's consent as a condition of continuing participation. (TCPS2 3.9)

An authorized third party is any person with the necessary legal authority to make decisions on behalf of a prospective participant who lacks the capacity to consent to participate, or to continue to participate, in a particular research project. This person should not be part of the research team and should adequately know the person whom they are representing to take into account any previously expressed opinions regarding participating in research. Family members and friends may also provide information to the authorized third party about the interests and previous wishes of prospective participants.

When an authorized third party is being used to consent on behalf of a person with diminished or developing capacity, the BC Common Clinical Informed Consent Form Template should be used to develop the consent form, and it should be amended to be clear that the third party is consenting on behalf of the research participant. The following paragraph or the like is required to appear in the consent form in cases where the participant assents to participate in the research:

The parent(s)/guardian(s)/authorized third party and the investigator are satisfied that the information contained in this consent form was explained to the child/potential participant to the extent that he/she is able to understand it, that all questions have been answered, and that the child/potential participant assents to participating in the research.

Inclusion of this statement in the consent form places the obligation on the authorized third party, who is providing consent, and on the investigator to ensure that the participant/child assents and understands the information in the consent form to the extent that he/she is able.

A separate assent document with wording aimed at the level of the potential participant may also be appropriate and is not precluded by the addition of this statement to the consent form. See Article 15.6 below.

Where individuals have signed a research directive indicating their preferences about future participation in research in the event that they lose capacity or upon death, researchers and authorized third parties should be guided by these directives during the consent process. (TCPS2 3.11) If a person who has signed a research directive retains sufficient capacity to assent or dissent to the research, and they decline to participate, their dissent must be respected.

Where an authorized third party has consented on behalf of an individual who lacks legal capacity, but that individual has some ability to understand the significance of the research, the researcher should determine the wishes of that individual with respect to participation. If this person "assents" to the research, they are agreeing with or concurring with the consent of their authorized third party. While the individuals assent would not be sufficient to permit them to participate in the absence of consent by an authorized third party, their expression of dissent or signs suggesting they do not wish to participate must be respected and precludes their participation. Those who may be capable of assent or dissent include:

1. those whose capacity is in the process of development, such as children whose capacity for judgment and self-direction is maturing;
2. those who once were capable of making an autonomous decision regarding consent but whose capacity is diminishing or fluctuating; and
3. those whose capacity remains only partially developed, such as those living with permanent cognitive impairment. (TCPS2 3.10)

UBC's REBs do not consider lack of assent or dissent to be equivalent to refusal to participate. Caution and special care should, however, be taken in these circumstances. The research must fit all of the criteria outlined in Article 15.2 and the third party decision maker must take into account any previous preferences regarding participation in research expressed by the potential research participant. The researcher should document the lack of assent or dissent in the research record. The researcher must respect any expressions or displays of dissent during participation in the research.

When a child under the age of majority is deemed to have the capacity to consent, they can consent for themselves, unless there is a legislative prohibition, which restricts their ability to consent in particular circumstances. In BC, there is no legislation that has been interpreted as restricting children with capacity to consent, from consenting to research.

However, in some situations parental agreement may be appropriate or necessary. For example, the research may be taking place in institutions that have specific requirements about research involving children or it may be sponsored by a company that also has requirements in this regard. In these cases, a parental consent form as well as a child's consent form may be necessary. For example, the Vancouver School Board requires parental consent for all research that is taking place in its schools. In these situations, researchers should seek consent from the capable child and consent from the parents, using separate forms. Both parties must consent before the research can take place. If the child consents and the parent does not, the child cannot participate in the research despite being fully able to consent. This is not UBC's REBs policy, rather it is due to the school board's requirements. In order to be able to conduct research within the Vancouver School Board, their requirements must be complied with. The same is true for sponsored studies where adult / parental consent is a requirement of the Sponsor.

In the same way that there are clearly examples of cases where it would be inappropriate or possibly even harmful to inform the parents of children capable of consenting to certain research about their child's participation, (e.g. some kinds of research concerning abortion or other sensitive subjects) there may be other instances where it would be appropriate or courteous to obtain the agreement of a capable child's parents, or at least to ensure that they are informed that the research is taking place. Researchers should consider the specific nature and context of their research, and determine what they deem to be appropriate. UBC's REBs will make the final determination as to what they deem to be necessary in the context of the research that they are reviewing.

The information described below must be conveyed in the consent form and in the Application for Ethical Review in ways that will be meaningful to prospective participants and the REB:

1. The type(s) of data to be collected and the period over which they will be collected (which in this guideline includes identifying data, such as names, initials, telephone numbers, addresses, personal health numbers, etc.);
2. The purpose(s) for which the data will be used;
3. The limits on the use, disclosure, and retention of data, including descriptions of access by other researchers, any planned linkages to other databases, and types of studies to be conducted;
4. The entity or person(s) who have custodianship of the data and the address of the database or registry;
5. The measures in place for protecting the security of the data and participant confidentiality, including a description of the de-identification or coding of the data and of what steps will be taken to ensure the security of the database (e.g., password protections, data encryption, secure rooms, etc.);
6. A description of who will have access to identifying data, the nature of that information, and who will have a key linking coded data to identifiable participants;
7. A description of any identifying data, or linked or coded data, or data that is fully de-linked and anonymised, that will be sent outside Canada, and to whom it will be sent (e.g. individuals, organizations, regulatory agencies), and where it will be stored (provide local address and country);
8. The risks associated with possible disclosure of identifying data, including non-physical risks associated with accidental disclosure of genetic or other information that could result in discrimination by employers, insurance providers, or others;
9. A description of any commercial uses for which the data may be used, including any disclaimers about participant remuneration;
10. Any foreseeable circumstances where disclosure of identifying data is required by law (e.g., for reportable diseases [Article 13.6.5] or child abuse [Article 13.6.4]);
11. Any anticipated secondary uses of identifying data from the research, and whether participant consent will subsequently be sought for such uses;
12. Any anticipated linkage of the data gathered in research with other data about participants (whether those data are contained in public or personal records);
13. Any modes of observation (e.g., photographs or videos) or access to information (e.g., sound recordings) in the research that allow identification of particular participants (see Article 13.5.6);
14. Any access participants have to the data and rights to amend or withdraw data or to withdraw permission to obtain data, including a description of who to contact for these purposes (requests to withdraw permission to obtain data must not be required in writing);
15. A description of how long the data will be retained and whether identifying data will be destroyed or returned to the participant.

In addition to the information described above, researchers must satisfy the REB of the following in the Application for Ethical Review:

1. A full description is provided of the data stewardship processes for overseeing the management and use of the data, including the main rules governing use of the database, the process by which access requests will be reviewed, and the organization to whom the researcher is accountable for the proper management of the data;
2. Data is being obtained from research participants only insofar as it is necessary for the research.
3. Specific and appropriate justification has been provided for collection and use of identifying data, including any use of identifying data on case report forms or other database or registry documents (e.g., names, initials, telephone numbers, addresses, personal health numbers, etc.).
4. De-identification of data will occur as quickly as possible.
5. Access to identifying data and to the key linking identifying data to de-identified data has been limited to the minimum number of properly trained personnel that is reasonable in the circumstances.
6. Database personnel have appropriate training in, and comply with, security and privacy safeguards.
7. Identifying data will not be retained for longer than is necessary to fulfill research purposes (at which time they should be destroyed or returned to the participant- see A. xvi above). [See AGN 8.6 and Food and Drug Act Regulations: Division 5 Section C.05.012 (4) regarding retention of records.]

Changes to 16.1 or 16.2 above require REB approval through the normal study amendment process.

The CREB may require additional information in the consent form or in the Application for Ethical Review.

Identifying/Identifiable Data: information that can directly or indirectly identify an individual. This includes information: a) that contains an individual's personally identifying information (e.g., name, initials, address, telephone number, date of birth, personal health numbers, full face photographic images, etc.), or b) for which there is a reasonable basis to believe the information could be used to identify an individual.

De-identified Data: information where an individual's identifying information has been removed, and where there is no reasonable basis to believe that the information could be used to identify an individual. De-identified data may nevertheless be coded (e.g. via a confidential master list created by the researcher) so that the information can be linked to the individual and his/her clinical or other records. See AGN 8.4 for further directions on coding that is consistent with de-identification of data.

Anonymous/anonymised data: this refers to information that cannot be linked back to an individual either directly or indirectly (i.e., the information contains no identifying information, no master list or coding remains anywhere linking a participant to the information, and there is no reasonable basis to believe that the information could be used to identify a participant).

UBC's REBs make case-by-case judgments about the merits of research in light of the risks posed. As radiation exposure escalates, expectations of risk minimization and prospect of direct benefit will proportionally escalate. This guidance focuses on improving communication with research participants about radiation risk.

When using radiation or radioactive materials in human participants, the study should be designed to use minimum radiation doses following prevailing medical radiation exposure guidance, and those that are as low as reasonably achievable (the "ALARA" principle).

Radiation exposure includes the dose from all radionuclide procedures and all diagnostic radiology procedures related to the research study, together with doses from other research studies in which the participant may be participating or has participated in previously. Repeated use of the same volunteers for different projects involving radiation exposure is discouraged. Similarly, it may be inappropriate to involve participants with substantial prior radiation exposure. UBC's REBs understand that the risk of exposure to radiation is cumulative over a lifetime.

While radiation is categorized by the FDA as a known carcinogen, considerations pertaining to informing participants of radiation risks need to be tailored to the particular circumstances of the study population. For example, communication of risk to cancer patients who may be participating in studies that involve exposure to radiation would be quite different than communication of risk to adults without cancer. Similarly, risks to adults over 50 are somewhat lower, and risks to children are higher, due to their heightened sensitivity.

UBC's REBs base their understanding of the risks of radiation on the European Commission document noted below.

"Radiation protection 99, Guidance on Medical Exposures in Medical and Biomedical Research, 1998" https://ec.europa.eu/energy/sites/ener/files/documents/099_en.pdf

The European Guidance describes the following primary categories of radiation risk:

Category 1: Effective doses less than 0.1 mSv (adults)

This category involves a risk (total detriment from the radiation exposure for normal participants of less than one in a million.

Category 2a: Effective dose range 0.1 - 1 mSv (adults)

This category involves risks of the order of one in a hundred thousand.

Category 2b: Effective dose range 1 - 10 mSv (adults)

This category involves risks to the irradiated individual of the order of one in ten thousand.

Category 3: Effective doses greater than >10 mSv (adults)

Here the risks to the irradiated individual are estimated at greater than one in a thousand.

The risks referenced in the categories, are "lifetime risk of death [from cancer] due to hematologic or solid organ malignancy".

The categories noted apply to healthy adults (those without cancer) under 50 years of age. The dose figures may be increased by a factor of 5 - 10 for individuals over 50. In the event that approval is being sought for research on children, the corresponding dose figures should be reduced by a factor of 2 or 3.

UBC's REBs (with the exception of the BC Cancer REB) recommend that the following principles be adhered to in all study-related communications about the risk of radiation exposure:

1. 1. State the effective dose (or dose range) in mSv.
   The conversion factor between the mSv and Radiation Equivalent Man (REM) units is 10mSv=1 rem.
2. Describe the exposure in terms of common life events, such as:
   Chest radiograph 0.02 mSv (The Royal College of Radiologists. Making the best use of clinical radiology services: referral guidelines. London: The Royal College of Radiologists, 2007, page 17, Table 2.)
   Natural Background radiation 2.4 mSv / year (Mettler FA, Bhargavan M, Faulkner K, Gilley DB, Gray JE, Ibbott GS, Lipoti JA, Mahesh M, McCrohan JL, Stabin MG, Thomadsen BR, Yoshizumi TT. Radiologic and nuclear medicine studies in the United States and worldwide: Frequency, radiation dose and comparison with other radiation sources - 1950 - 2007.)
   A guide to the exposure associated with various other procedures is available at http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray#3
3. Describe the risk in absolute based on the categories and age adjustments in section 20.1.2. and disclose that the risk being referred to is "your lifetime risk of dying from cancer".
   For example, the additional risk of fatal cancer from a single 20 mSv exposure in a person <50 years old is 1 in 1000 or 0.1%.
4. Mention the time horizon over which the risk occurs. For example, "If it were to occur, it could take many years or decades for you to develop cancer related to this study."
   The latent period for cancer induction is estimated to be 6 to 10 years for blood borne cancers (leukemia, lymphoma) and 10 to 25 years for solid organ cancers.
5. Disclose to research participants that the risk from all sources of radiation is cumulative over a lifetime.

Investigators requiring assistance in estimating the levels of risk or the practical equivalents should speak with the Radiation Protection Officer of their institution. Researchers conducting studies with participants who have cancer should consult with the BC Cancer REB concerning the need to include any specific information pertaining to radiation risks in their proposed studies.

Researchers conducting studies utilizing positron-emitting radiopharmaceuticals should consult with the 2006 interim compliance policy and guidance documents found at:

http://www.hc-sc.gc.ca/dhp-mps/compli-conform/info-prod/drugs-drogues/pol_0053_tc-tm-eng.php

References

Health Canada:

http://www.hc-sc.gc.ca/dhp-mps/compli-conform/clini-pract-prat/docs/gui_68_tc-tm-eng.php

Health Canada:

"Factors considered in the assessment of risks involved in the use of positron emitting radiopharmaceuticals in basic research involving humans"

FDA:

http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Oncology/ucm196484.htm#dose

International Commission on Radiological Protection)[§361.1(b)(3)(iv)].

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=361.1

Medical Internal Radiation Dose Committee of the Society of Nuclear Medicine

http://www.snm.org/index.cfm?PageID=1372

The European Commission document "Radiation protection 99, Guidance on Medical Exposures in Medical and Biomedical Research, 1998" https://ec.europa.eu/energy/sites/ener/files/documents/099_en.pdf

Radiology Info: A guide to the exposure associated with various other procedures is available at http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray#3