Revised: March 11, 2011
UBC BCCA Research Ethics Board
Frequently Asked Questions (FAQ's)
I am uncertain as to where to submit my ethics application and who can submit to the BCCA REB
What is research and when does it require REB approval?
Quality assurance versus research requiring ethics approval
"Sub-study" or "extension study" versus new study
Are there guidelines for Expanded Access Protocols (EAP)?
What is a "normal" participant?
DATA SAFETY MONITORING BOARD (DSMB)
When is a DSMB required?
Does BCCA have a DSMB?
Person Obtaining Consent
Does a person obtaining consent have to be listed as a co-investigator?
If the "Person Obtaining Consent" signs 1, 2, 3 days after subject signs, is consent still valid?
Re-Consenting (Renewal of Consent)
Consent indicates reports might be sent to or inspected by Health Canada-why?
Listing of Investigators and temporary leave of absences
SUBJECT HANDOUTS AND ADVERTISEMENTS
Do "Subject Handouts" require REB approval?
Can an advertisement be posted at BCCA for research conducted elsewhere or does it require BCCA ethics approval?
RETENTION OF SUBJECT'S SAMPLES
How long must subject samples be retained and must this be stated on the consent or just the protocol?
When should a close-out visit be done by the sponsor?
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Q. What is research and when does research require REB Approval?
(Revised Dec 10, 2010)
The intent to publish a project does not solely determine whether ethics approval is required, rather it is the nature or purpose of the project that determines whether ethics approval is required.
The guiding principle governing human research ethics review in Canada is the Tri-Council Policy Statement (TCPS).
TCPS-2 Chapter 2: Scope of Research Ethics Review defines the general categories of research that require REB review: http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/chapter2-chapitre2/#toc02-1a
Note re Atricle 2.1 This article makes it clear that retrospective approval is not acceptable. The REB cannot give retrospective approval but it can provide a review when the project is submitted, and if the project is acceptable, approve it. However, that will mean that the official REB approval will be dated after the project was actually initiated. That, in turn, may mean that you face an objection from a journal or will need to provide the journal with an explanation as to why the dates are out of order. The journal may or may not accept your explanation. Alternatively, if a project was started before January 2005, it was initiated at a time when retrospective reviews of existing data did not require REB approval at BCCA. The REB chair can provide a letter stating this if requested by the journal after you provide this explanation.
Articles 2.2 to 2.6 describes projects that are exempt and do not require REB reivew such as Quality assurance and quality improvment studies. If your project is entirely for internal quality improvement or quality assurance, or educational testing (this can include student or resident reviews of treatment outcomes or treatment policy review), it does not fit the definition of research and does not require REB review. These types of projects may still raise ethical issues that would benefit from careful consideration by an individual or a body capable of providing some independent guidance, other than an REB.
A case report (retrospective analysis) of one or two clinical cases also does not require REB review, however more than two cases requires ethics review/approval.
The REB recognizes that it is difficult to determine the difference between an internal quality assurance (QA) project versus a research project requiring ethics approval because often the methodology is the same.
The Vancouver Coastal Health and Providence Health Care have developed a "VCH/PHC QI & REB review checklist" to help researchers distinguish between QA and research studies, which is located on the VCH webpage: http://www.vchri.ca/s/Home.asp or click on: http://www.vchri.ca/i/doc/Guidance_ResearchEthicsBoard.doc
For further insights into approaches for classifying studies as QA or formal research, you may consult the following link: http://www.ahfmr.ca/arecci/pdf/ARECCI%20Ethics%20Guidelines%20FINAL(ISBN)%20Aug%2025%2008.pdf
If after reviewing the above, there is uncertainty about whether the project is QA or research requiring ethics approval, it would be prudent to submit the project to the REB using the on-line ethics application RISe system for review because if it is later considered to have been research that should have been submitted, the REB cannot provide retrospective ethics approval for the project. If the REB deems the submitted project to be QA, an acknowledgment letter will be issued in RISe confirming this (rather than issuing a research project approval certificate). The application will then be terminated and moved to the "inactive" tab in RISe. QA projects do not fall under the purview of the Research Ethics Board and will not need to meet any further REB requirements. However, QA projects should still adhere to basic ethical principles particularly those regarding protection of privacy and confidentiality as applicable to the project.
If submitting the project to the REB, see Characteristics of a Project which explains what the BCCA REB looks for in any project submitted for review /approval.
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Q. Are there guidelines for Expanded Access Protocols (EAP)?
Yes, BCCA guidelines for Expanded Access Protocols are posted under the New Applications webpage
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Q. I am uncertain as to where to submit my ethics application and who can submit to the BCCA REB. (Revised January 30, 2007, November 11, 2008)
1. If you are BCCA staff or personnel
Designate a "BCCA" Principal Investigator who is responsible for the overall study and submitting ethics applications to the BCCA REB for that study. If submitting an ethics application to the BCCA REB the PI must have a BCCA appointment and the application must be approved by a BCCA Department Head. Examples of acceptable BCCA appointments include but are not limited to full or part time research scientist, physician, nursing, pharmacy, patient and family services, radiation therapy, dental or nutritional consulting staff; full time residents, fellows, graduate students or other trainees enrolled in programs supervised by BCCA staff.
The principle is that the PI must have a sufficiently clear connection to BCCA that there is a reasonable assumption that the PI will feel bound by requirements placed on her or his performance of the research by BCCA.
a) Clinical research projects must be submitted to the UBC BCCA REB for approval.
b) Behavioural research projects may be submitted to either the UBC BCCA REB or the UBC Behavioural Research Ethics Board (UBC BREB). If the project will be wholly or in part conducted at BCCA and is submitted to the UBC BREB, the application must identify the BCCA participating sites and there must be at least one BCCA Coinvestigator on the study but submission to the BCCA REB for the same project is not required and no additional documentation is required by the BCCA REB.
Note: The ethics approval applies to research ethics issues only. The ethics approval does not obligate an institution or any of its departments to proceed with activation of the study. Anyone conducting research, behavioural or otherwise, at the BC Cancer Agency, must make sure they obtain approval from any BCCA Department whose resources are affected by the conduct of the study and to identify and ensure that institutional policies such as those related to conflict of interest and privacy protection are followed and that resource impacts from the study are properly negotiated. The Principal Investigator is responsible for identifying and meeting those requirements.
2. If you are a non-BCCA researcher
Non-BCCA researchers conducting research on humans, or material or information derived from identifiable humans, to be carried out ONLY at a BCCA facility, must designate a Principal Investigator who has a BCCA staff appointment (see above) and obtain ethics approval from the BCCA REB.
Non-BCCA researchers conducting research on humans, or material or information derived from identifiable humans to be carried out at a BCCA facility and a non-BCCA facility must do one of the following:
a) Designate a Principal Investigator who has a BCCA staff appointment (see item 1. above) and submit an application to the BCCA REB for ethics approval. Note: The PI is responsible for identifying and meeting any other facilities' requirements where they plan to conduct the study.
b) Obtain ethics approval from one of the other UBC REB's (see the One Board of Record agreement below) and ensure that the BCCA participating sites are listed in the ethics application and that there is at least one BCCA co-investigator on the study. Submission to the BCCA REB for the same project is not required and no additional documentation is required by the BCCA REB as per the "One UBC Research Ethics Board of Record agreement noted below). However, anyone conducting research at the BC Cancer Agency must make sure they obtain approval from any BCCA "Department" whose resources are affected by the conduct of the study and may be requested to attach applicable letter(s) of department approval to their application if submitting to a UBC REB other than the BCCA REB. The Principal Investigator is responsible for identifying and meeting those requirements and any other facilities' requirements where they plan to conduct the study.
In all cases, ethics approval applies to research ethics isssues only. The ethics approval does not obligate an institution or any of its departments to proceed with activation of the study. Anyone conducting research, behavioural or otherwise, at the BC Cancer Agency, must make sure they obtain approval from any BCCA Department whose resources are affected by the conduct of the study and to identify and ensure that institutional policies such as those related to conflict of interest and privacy protection are followed and that resource impacts from the study are properly negotiated. The Principal Investigator is responsible for identifying and meeting those requirements.
One UBC Research Ethics Board of Record
Effective March 21, 2007, the UBC Research Ethics Boards agreed that each new research study reviewed by a UBC REB should have a single REB of Record. This is a change in procedure from the previous policy of Reciprocal Review. This now includes all 6 UBC REBs
The purpose of implementing one REB of Record is to avoid the requirement for multiple formal ethical reviews of the same research study. The need to identify one of the UBC REBs to be the REB of Record arises when the same Principal Investigator is conducting the same research project at more than one institution under the jurisdiction of more than one UBC REB.
Current projects that have been approved by more than one UBC REB must continue to submit to both REB's until completion of the project. However, under this new policy, when a new study is submitted to a UBC REB, the investigator is only required to submit the new application to one of the UBC REB's listed below. The UBC REB that initially reviews and approves the research study will become the REB of Record for the study, and all subsequent ethical supervision of that study.
To ensure that institutional specific ethics requirements are met, the Chair of the UBC REB for an institution involved in the conduct of the study that falls under their jurisdiction, may view the application and study documents approved by the REB of Record. If that UBC REB Chair has questions or concerns, these will be directed to the Chair of the REB of Record for resolution.
One UBC Board of Record Agreement.pdf
This agreement document is pending revision - in the interim this applies to all of the affiliated UBC REBs for human research which are;
- UBC BC Cancer Agency REB (BCCA REB)
- UBC Children's & Women's (C&W REB)
- UBC Providence (PHC REB),
- UBC Clinical REB (CREB),
- UBC Behavioural REBs (BREB)
- UBC Okanagan BREB (BREB-O)
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Q. What is a "normal" participant?
Generally, a normal participant refers to a randomly chosen member of the general population. Any individuals chosen for enrollment in a trial based on specific baseline characteristics are, by definition, not "normal" individuals for this purpose.
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Q. I want to add a "sub-study" or "extension study" should this be submitted as an amendment to a previously approved project or a new study?
1. The substudy consists simply of additional testing that will be done on the subjects or specimens already included in the original study; or
2. The substudy is simply an extension of the original study for a longer period of time; or
3. The substudy can be reasonably considered an extension of the original study for the purpose of expanding what will be learned from the conduct of the original study without extending into wholly novel areas of investigation.
A substudy should be considered a part of the original study and submitted for approval as an amendment to the original study if
A substudy should be considered a new study, requiring independent review and approval by the REB if
1. The new study extends into areas of investigation that are clearly beyond those reasonably included in the intent of the original study or amendments to the original study; or
2. The new study will include subjects or specimens that were not included in the original study or amendments to the original study.
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Note that there may be only one project title under one REB number so that all documents connected to that study including previous consent documents, contracts and descriptions of access to data can be linked to all projects done under that particular study. If it is thought desirable by the investigators for the substudy to be noted in the overall study title the original title can be amended by adding an extension. For example, if the original title was "A study of powermycin for breast cancer" and the substudy title is "A study of the cardiac effects of powermycin in subjects being treated for breast cancer" and the investigators wish to have the substudy noted in a new title, one acceptable new title would be "A study of powermycin for breast cancer including a substudy of the cardiac effects of powermycin."
If amending the title in this manner does not meet the requirement of the sponsor or principal investigator, then an application must be submitted as a new project under the new title and the REB informed that the new study is related to a previous project noting the title and REB number of that original project. The original project will remain ongoing until the REB is notified that it is completed.
Data Safety Monitoring Board (DSMB)
Q. When is a Data Safety Monitoring Board (DSMB) required?
A DSMB is only required for phase III or phase IV, or complex phase II trials.You will not need a DSMB for a marketed product being used for the purpose and in the manner for which it is marketed. You will need a DSMB if you plan to have a control group or a randomization or any manoeuvre that could place an individual at risk of a side effect or missing out on a benefit.
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Q. Does the BC Cancer Agency (BCCA) have a Data Safety Management Board (DSMB)?
No, the BCCA does not have a DSMB. Most trials done at BCCA already have a DSMB that has been constituted by the sponsor of the trial, usually a cooperative group DSMB such as the NCIC Clinical Trials Group DSMB or an independent DSMB chartered by the pharmaceutical company sponsoring the trial.
For trials done at BCCA which do not have a sponsor-organized DSMB, the investigators are responsible to set up the DSMB for their trial. Typically this means assembling a volunteer set of at least three individuals, one with experience in the area of the research, one with statistical background and at least one to three others with clinical trials experience.
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Q. Who can be a witness?
Effective November 27, 2008 a witness signature is allowed but no longer required except under certain circumstances.
(Refer to UBC CREB guideline: http://rise.ubc.ca/helpCenter/GN/CREB_Guidance_Notes.html#Guide39.8 )
If a witness signature is required, the witness signature designates only that the subject (or their legal representative) actually signed the form. For this reason, the witness should generally have been present during the consent process. The signature is NOT intended to verify that the subject actually understood the information conveyed, although a witness could refuse to sign if they had a concern about this. Any person who can certify that the person signing is the actual subject can be a witness including the study nurse, the clinic nurse, a clerk, a relative, another doctor etc., as long as they are not the "Person Obtaining Consent" (see Person Obtaining Consent).
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Q. If the witness signature is missing is the consent still valid?
If there is a requirement for a witness signature (refer to the UBC CREB guidelines http://rise.ubc.ca/helpCenter/GN/CREB_Guidance_Notes.html#Guide39.8 )
then the consent is not valid if there is no witness signature to verify that the signer was really the subject. Obviously, the subject and witness must sign on the same date.
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Q. If the witness signature is missing will the subject have to be re-consented?
If there is a requirement for the witness signature (refer to UBC CREB guidelines http://rise.ubc.ca/helpCenter/GN/CREB_Guidance_Notes.html#Guide39.8 ) then the easiest and least confusing way to deal with this would be to have the subject write a very short note on the original consent form itself indicating that the signature already obtained is valid and sign and date that note. The witness should then sign indicating that the signatures are valid. That way you do not have to generate a second, potentially confusingly dated, document.
(also see "deficient consent")
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Q. Who is the "Person Obtaining Consent"?
This must be a person sufficiently familiar with the study, the disease being treated and the process of informed consent to be able to obtain properly informed consent and, thus, will usually be the investigator or a designated research assistant. Reminder for investigator: The investigator should independently document the obtaining of informed consent in the medical record, noting date, the subject's full understanding of the risks and benefits of enrollment and the voluntary nature of participation. (See BCCA REB Policy on Person Obtaining Consent)
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Q. Does a person obtaining consent have to be listed as a co-investigator?
No. The Principal Investigator may delegate consenting authority to any person that is sufficiently familiar with the study, the disease being treated, and the process of informed consent. This person does not have to be listed as a co-investigator for the study.
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Q. If the "Person Obtaining Consent" signs the consent form 1, 2, 3 days after the subject signs, is the consent still valid?
Yes, the consent is considered valid as soon as the subject and if applicale, the witness have signed. As long as the interval is short (just a few days) between their signatures and that of the Person Obtaining Consent it will remain valid. It is always preferable for the dates of all the signatures to match. If that is not possible the investigator should clearly document why the dates do not match. There are times when a consent cannot be signed by the Person Obtaining Consent for a day or two after the subject signs such as in a mailed or faxed consent (see UBC CREB Guide 32.1.1 –Mailed or Faxed Consents), however, the consent is not valid if the subject or the witness (if applicable) signed "after the fact". This means that subjects cannot date their signature earlier than the actual date they signed (see UBC CREB Guide 39.3 – Timing of the Consent. It is quite undesirable for the subject to undergo any study related evaluations, tests, procedures or especially treatments before all signatures have been obtained. The principal investigator opens him or herself to criticism for not having verified that proper consent has been obtained if anything happens to the subject in the interval between subject signature and investigator signature.
Enrollment in the study starts as soon as the consent is validly signed by the subject and that subject must be accounted for thereafter. Imagine a situation in which the subject gives consent and then dies of an allergic reaction while undergoing a CT scan required by the study the same day as she signed. That subject has enrolled on the trial and that serious adverse event counts even if the Person Obtaining Consent has not yet signed.
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Q. What should be done if consent has been acted on and then discovered to be deficient?
In any of these or other cases, if a consent has been obtained and acted upon then discovered to be deficient, the easiest approach is to directly note on the original consent how this is being corrected, obtain the relevant signatures and separately document in the medical record exactly what was done and why. If the correction must be more elaborate than can be described in a few words written on the original consent form then a new consent form can be used but the medical record should record all the relevant details including the fact that actions were undertaken based on the initially signed document, which must be retained.
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Re-Consenting (Renewal of Consent)
Q. Will the REB note on their certificate of approval for revised consent forms, that subjects "do" or "do not" require re-consenting based on the newly revised consent?
No, the REB does not note this on the certifcate of approval. The term re-consent is confusing. A better term is renewal of consent because it makes clear that renewal of consent applies in a situation in which prior valid consent was obtained and the renewal is required because new information has become available that a reasonable subject would want to be aware of because the new information may affect their willingness to continue to participate or some newly discovered consequence of past participation has come to light. In general, the sponsor will indicate when renewal of consent is required. The REB will indicate when, in its judgment, renewal of consent is required, however the REB cannot be expected to anticipate all the situations in which the sponsor may wish to do so.
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Q. Eligibility Criteria – is this a new requirement in consent forms?
Actually consent forms have always included information concerning who should be on the trial and who should not. This is not a new requirement. However, we have noted that the information is often scattered or incomplete therefore the REB now requires this to be gathered in two recognizable sections in the consent document.
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Q. Where do we draw the line when listing eligibility on the consent?
Common sense is the best guideline here. The lists of inclusion and exclusion criteria should state items that are helpful for the subject to be sure it is appropriate to enroll and include those that the subject would be reasonably expected to know (they may have personal information that the investigators are not aware of that could pose a risk should they enroll). Thus, reasonable exclusions might be for a history of a heart attack or a history of hepatitis. Reasonable inclusions would include the correct diagnosis, the general timing of the progress of the cancer, for example, after two or more recurrences.
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Q. Some information may cause more confusion than clarification for the subject.
The purpose of these sections is obviously to decrease confusion. The consent form cannot be exhaustive. It is supposed to provide what a reasonable person would want to know to be able to give fully informed consent to participate. The term "eligible" should be avoided in the consent form as this may imply that those who do not qualify for inclusion are a failure of some sort. The real purpose of inclusion and exclusion criteria is first to insure that subjects do not enroll on trials that would be unsafe for them and second to be sure that the data from the trial are scientifically interpretable.
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Q. The consent template indicates that reports might be sent to Health Canada or that Health Canada may inspect the primary records or data at BCCA, why?
Health Canada is the branch of the Canadian government that regulates human research. As such it has broad powers to issue regulations and to monitor compliance. This is all described in the legislation that empowers Health Canada to do this job. You can find out more about Health Canada's role in the regulation of human research on their website.
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Subject Handouts and Advertisements
Q. Do "Subject handouts" have to be submitted to the REB?
Written information, which is entirely trial specific and MUST be supplied to the subject for them to be on the trial (not just treated for their cancer) must be approved by the REB. Information that is supplied to patients whether they are on the trial or not, or for the standard treatments given during trials, does not need REB review. For example, in an immunization trial all subjects may receive standard chemotherapy prior to the experimental immunization. The standard chemotherapy regimen is used for both trial subjects and patients not on a trial. There is no need for REB review of the standard chemotherapy handouts that are given to the subject. Or, for example, a general pamphlet describing vaccine treatment prepared by the company for any individual interested in the topic whether they are a patient or not or whether they will be a subject on the trial or not, does not need approval. However, if a subject could not be on the trial without receiving a document, for example, a required questionnaire, that document must be approved.
(see CREB Guide 6.2 and BCCA REB policy on subject handouts)
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Q. Can an advertisement be posted at the BCCA for research that is being conducted elsewhere or does it require BCCA ethics approval?
Occasionally non-BCCA researchers conducting projects involving humans ask to be allowed to advertise their research project within BCCA facilities and the question arises whether such research requires BCCA REB approval.
Research being carried out elsewhere by non-BCCA staff is not under BCCA jurisdiction. If research is being done elsewhere and a researcher would like to advertise the project in BCCA facilities for the purpose of recruiting volunteers BCCA has no ethical jurisdiction and therefore this is not a BCCA REB issue. However, any such advertisements do need to meet BCCA advertising standards and approval about which the researcher should contact the BCCA Administrative Offices.
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Retention of Subject's Samples
Q. How long must subject samples be retained and must the period of retention be stated on the subject consent or just in the protocol?
Samples can be retained as long as the investigators wish to do so. They must, however, indicate how long the samples will be retained (3 years, 10 years, indefinitely, until they are all used up, are examples of acceptable wording) in the consent form and the length of time must be justified in the protocol. The REB will not permit retention longer than can be clearly justified.
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(Also refer to Useful Links for links to these Privacy Laws)
Q. What is PIPEDA and HIPAA and are we compliant?
PIPEDA (Personal Information Protection and Electronic Documents Act) is Canadian federal legislation governing the collection and use of personal information by commercial entities. It is intended to strengthen protection of confidentiality of private citizens whose personal information has been gathered by commercial entities. It is not intended to govern information gathered in the course of medical research. However, as with any complex new legislation, there is much confusion about this among various companies. The situation is made more complex by the United States legislation entitled Health Insurance Portability and Accountability Act of 1996 (HIPAA). The HIPAA regulations in the States do govern procedures for handling all medical records including those gathered for research. HIPAA regulations do not govern what we do in Canada so for the moment we do not need to be concerned about them. More important, our confidentiality policies make us HIPAA compliant anyway so this should not pose a problem.
The spirit of the PIPEDA legislation is that individuals be provided with effective guarantees of confidentiality. Our policies concerning confidentiality of information gathered in clinical research projects done at BCCA already provide such guarantees. So we are already in compliance with the spirit of the PIPEDA legislation and, thus, have met our ethical obligations and need not change our current policies. The chairs of the four REB's within UBC are actively discussing how to provide a common response to requests for modification of our policies to reflect what are usually mis-interpretations of PIPEDA requirements. Until these discussions reach a conclusion there is no need to alter our current policies and consent format.
The following statement from the chairs of the UBC REB's reflects their common approach to this issue: Federal privacy legislation applying to the private sector in Canada (PIPEDA) came into effect in January 2004. This has caused some industrial research sponsors to request modifications to research consent forms, which either replace or augment the UBC REB-required confidentiality wording. Some of these statements are over one page in length. The UBC REBs are in the process of determining the exact legal need for such statements and developing a policy which allows sponsors to meet PIPEDA requirements without adding unnecessary length and complexity to consent forms. To this end, and until further notice, the UBC REBs will expect that any request for changes to the confidentiality section of consent forms will be accompanied by a detailed explanation for each phrase, including specific reference to the portion of the PIPEDA legislation which motivates it. Using this information, the UBC REBs hope to gauge the legal basis for these statements and arrive at a reasonable compromise which communicates the legally required information efficiently and is consistent with the best interests of subjects.
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Q. When should a close-out visit be done by a sponsor
The timing of all monitoring visits, including the "close out" visit is entirely up to the sponsor. The REB will consider a trial closed to accrual when the last subject has been enrolled and accrual is officially closed. The REB will not consider the trial closed to follow-up until all reporting of all data has been completed. Until then the trial is open and annual renewal of approval by the REB is necessary. The sponsor can conduct a "close out" visit whenever desired but that does not close the trial locally until the above criteria have been met.
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