UBC Clinical Research Ethics Board Guidance Notes for New Applications for Clinical Ethical Review
Version Approved by the Clinical Research Ethics Board (CREB) 26 Mar 2002
1st update 07 May 2003, 2nd update 17 Jul 2003, 3rd update 31 Jul 2003, 4th update 19 Sep 2003, 5th update 15 Nov 2003, 6th update 24 Sep 2004, 7th update 02 Feb 2005, 8th update 22 Dec 2005, 9th update 21 Aug 2006 (for RISe), 10th update 30 Mar 2007, 11th update 02 Dec 2007, 12th update 03 Jul 2008, 13th update 24 Jul 2008, 14th update 15 Sep 2008, 15th update 24 Oct 2008, 16th update 27 Nov 2008, PLEASE NOTE THAT ALL UPDATES ARE DATED. THE MOST RECENT UPDATES ARE HIGHLIGHTED IN YELLOW.
About the Guidance Notes
The following Guidance Notes (GNs), which comprise the UBC Clinical Research Ethics Board (CREB) standard operating procedures, policies, and advice, are intended to ensure that applicants have the necessary information to be able to fill out the Application for Clinical Ethical Review correctly and to construct consent forms that meet CREB standards.
It is the responsibility of the researcher(s) to ensure that the information contained in each GN is applied in a manner appropriate to each individual study for both the Application Form and any accompanying documentation. The CREB requires a complete response to each question in the Application Form.
The Application Form is a password-protected document. A number of the Application Form boxes require information to be entered into fixed fields. Information has to be entered directly into these fields and can also be copied and pasted from a Word document. All investigators are responsible for understanding and adhering to the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS) (1998) and other relevant guidelines. These Guidance Notes are not intended to be a substitute for this responsibility. Refer to the original documents for complete information.
About the UBC Clinical Research Ethics Board
The CREB procedures/policies correspond to, and therefore comply with, the pertinent TCPS as well as with the ICH Good Clinical Practice Guidelines (ICH GCPs) (1997). Both of these documents have their origin in the ethical principles that were developed in the Declaration of Helsinki (1964).
Canadian Research Ethics Boards (REBs) that conduct ethical reviews of clinical trials using drugs, radiopharmaceuticals, natural health products and medical devices are also regulated by the following Health Canada legislation and fulfill specific obligations under these Acts.
The purpose of the UBC CREB is to determine whether the research question or hypothesis is scientifically and therefore ethically valid; and, if so, whether the research is in compliance with the relevant ethical requirements for carrying out research involving human subjects. In accordance with TCPS Article 1.1 and ICH GCP Article 3.3.6, the research study cannot begin until the CREB issues its written approval of the research proposal.
Composition and Function of the CREB
In order to be compliant with the TCPS , the CREB membership is comprised of medical doctors and/or scientists with expertise in a variety of clinical fields, as well as an ethicist, a lay person(s) (no affiliation with the university), and a person knowledgeable in the relevant law. The medical doctors/scientists function as primary reviewers and are assigned a specific number of new applications to review in addition to applications for amendments and renewals and responses to deferral notices. Primary reviewers are responsible for reviewing the full study protocol and the Investigator's Brochure in addition to the consent forms and any other accompanying documentation. The non-primary reviewer members of the CREB review all studies that go forward to a board meeting. Their review includes all application forms, consent forms and accompanying documentation excluding the protocol and Investigator's Brochure.
The application forms and accompanying documentation are provided to the CREB members approximately one week before the meeting day. This allows the CREB members to review each application thoroughly before attending the meeting. The number of total studies (i.e. new applications, amendments, renewals and responses to deferral notices) for review per meeting typically ranges between twenty and forty.
At the CREB meeting, the primary reviewers present a summary of the proposal and their assessment of it. Decisions arising from the board meeting reflect the collective views of the members.
Consistent with TCPS Article 1.9, the CREB will accommodate reasonable requests from researchers to participate in discussions about their proposals, but not requests to be present when the CREB is making its decision.
The CREB may at times seek its own confidential external review of the research if the CREB decides that additional expert opinion is required prior to their review or approval (refer to ICH GCP Article 3.2.6).
Help with any aspect of the submission, information regarding meeting schedules, or the status of a study may be obtained from the applicable REB below:
SUBMISSION CRITERIA FOR CLINICAL RESEARCH
Who Must Submit to the CREB
The UBC CREB operates under the authority of UBC Policy #89 on 'Research and Other Studies Involving Human Subjects' (approved March 2002).
Any project (research or other study) involving human subjects in clinical procedures, which is carried out by a person connected with the University, must be reviewed and approved by one of the UBC Research Ethics Boards before the research begins. Clinical projects are those involving surgery, the administration of drugs, medical imaging or other diagnostic techniques, biopsies, the taking of blood or other specimens, the review of clinical medical records, and any invasive procedure involving an element of risk should be submitted to the CREB. A clinical research project that also includes questionnaires or interviews should also be submitted to the CREB.
The CREB does not under any circumstances review nor grant approval for research which has already been conducted. Requests for such review to satisfy, for example, publication requirements, will not be entertained.
The CREB will only review research that is undertaken by investigators who have an appointment at either UBC or an affiliated institution. See below for information that pertains to investigators conducting research at both a Providence Healthcare site and a UBC affiliated site (i.e. VCHA). See below for information pertaining to research conducted at BC Cancer Agency.
Research Conducted at Providence Healthcare and BC Cancer Agency (Updated 30 March 2007)
All UBC Research Ethics Boards (CREB, BREB, Providence Healthcare REB and BC Cancer Agency REB) have agreed, effective March 21, 2007, that each research study reviewed by a UBC REB should have a single REB of Record. This is a change in procedure from our previous policy of Reciprocal Review.
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 several possible REBs to be the REB of Record arises when the same Principal Investigator is conducting research at more than one institution under the UBC REBs’ jurisdiction.
Under this new policy, the UBC REB that initially reviews a research study normally becomes the REB of Record for the study, but occasionally a project is referred to another of the REBs. Once established as the REB of Record, that REB should deal with all subsequent ethical supervision of that study. This means that the investigator is only required to submit all post approval activity submissions to one REB, regardless of whether or not the research is being conducted at another institution under UBC REBs’ jurisdiction.
Although there is one REB of Record, in order to ensure that institutional specific ethics requirements are being met, the Chair and Manager of each UBC REB for the institution(s) involved in the research have the ability to view the application approved by the REB of Record. If the REB Chair of any institution involved in the research has questions or concerns, these will be directed to the REB Chair of the REB of Record for resolution. The REB Chair of any institution involved as a research site may refer a question or concern to the REB of Record at any time (i.e. before or after the study has been approved by the REB of Record).
The Providence Healthcare Research Ethics Board (PHC REB) should be the REB of Record for all studies carried out at a Providence Healthcare site, and for studies being conducted at other sites by Principal Investigators with Providence Healthcare appointments. Please note that Providence Health Care Research Ethics Board reviews both clinical and behavioural applications. The Application Form for ethical review should be sent to the PHC REB for review by selecting the Providence Healthcare Research Ethics Board in question 4.1 in the application form. For details about the institutional requirements of Providence Health Care, contact Nesa Kruse at Nkruse@providencehealth.bc.ca .
The BC Cancer Agency Research Ethics Board (BCCA REB) should be the REB of Record for all studies carried out at the BC Cancer Agency, and for cancer research studies related to malignant disease conducted at other sites by researchers with BC Cancer Agency appointments. Please note that BC Cancer Agency Research Ethics Board reviews both clinical and behavioural applications. The Application Form for ethical review should be sent to the BCCA REB for review by selecting the BC Cancer Agency Research Ethics Board in question 4.1 in the application form.
Who Must Submit to the UBC Behavioural Research Ethics Board
Research involving human subjects may involve potential invasions of privacy by asking subjects to participate in studies that use, for example, questionnaires, interviews/focus groups, observation, deception, testing, video and audio taping. Research that is limited to these types of data collection methods, but which may also include the collection of a subject's health information (29 July 2003), must be submitted to the Behavioural Research Ethics Board (BREB) for review.
Please note that the Providence Health Care Research Ethics Board and BC Cancer Agency Research Ethics Board also review behavioural research studies that fall under their jurisdiction as outlined above.
At the discretion of the Chairs and
Managers of the UBC REBs, a submission may be re-directed to a more
It is strongly recommended that applicants contact the CREB office should they require advice on whether to submit for Full Board or Expedited review. Submissions for Expedited review that are referred to the Full Board will increase turnaround time substantially.
#1: Principal Investigator
1.1.1 All Principal Investigators
All Principal Investigators must have a faculty appointment at UBC or a staff appointment at an affiliated institution. The Principal Investigator (PI) bears the overall responsibility for the conduct of the study, including the activities of co-investigators, who are assumed to be acting under the delegated authority of the PI, and is required to act within the requirements of the TCPS.
Investigators can request that multiple “sites” conducting the same study operate at the same institution (eg, a stroke researcher and a cardiologist researcher wish to each act as the PI for separate “sites” of a multicentre trial being conducted at one hospital). In such cases, a legitimate reason for operating in this way must be provided to the CREB. Furthermore, the CREB will request that the two “sites” coordinate all interactions with the CREB (e.g. amendments, renewals, Serious Adverse Events) as a method of streamlining the approval processes and preventing divergence in consent form disclosures.
1.1.2 Investigators Conducting Clinical Trials Regulated by Health Canada (24 September 2004)
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 regulations that govern each type of experimental therapy. The ICH: GCP guidelines specify additional obligations for investigators conducting clinical drug trials. Refer to GN 12 for further details.
Investigator-initiated Clinical Trials
1.1.3 Investigators Conducting Clinical Trials Funded And/Or Regulated By the United States Federal Government (24 September 2004)
Investigators that receive funding for studies conducted by a U.S. government department and/or its agencies (e.g. Department of Health and Human Services (DHHS)/National Institute of Health/National Cancer Institute, Department of Defence, U.S. Army) OR are conducting studies regulated by the Food and Drug Administration are subject to the pertinent U.S. federal regulations. These are part of the Code of Federal Regulations (CFR) mandated by the United States government. The U.S. regulations that pertain to clinical research are:
1.2 CHANGE IN PRINCIPAL INVESTIGATOR
When the PI terminates his or her employment/association with UBC, the PI must inform the CREB by submitting an amendment that a new PI (meeting the above criteria in 1.1.1) will assume this role for the study for the CREB approval to be considered valid.
#2: Submission Criteria for Full Board or Expedited Review (Updated 30 March 2007)
The process used to review the new applications varies according to the level of risk (i.e. is proportionate to the level of risk) that the subject could experience as a result of the particular type of research procedure used, and is described below. [BACK TO TABLE OF CONTENTS]
2.1 MINIMAL RISK RESEARCH STUDIES (Updated 30 March 2007)
Minimal Risk is defined in the TCPS as: "if potential subjects 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 subject in those aspects of his or her everyday life that relate to the research then the research can be regarded as within the range of minimal risk" [TCPS Section C1].
Minimal risk applications generally do not go to the Full Board, but are reviewed only by either the Chair or Associate Chair(s). The CREB delegates the authority to the Chair (or designate) to review new applications that meet the designated criteria for expedited review (see GN #2.1.2 below). Approvals arising from this review are reported, before the Certificate of Approval is issued, to the full CREB as per the requirements of TCPS Article 1.6.
The expedited review process also includes the Chair's (or designate's) review of amendments, renewals, responses to Notices of Ethical Review and any other correspondence.
The CREB retains the right to decide to put any application submitted for minimal risk review forward for Full Board Review. The applicant will be notified of this change. There is no deadline for applications that meet the Minimal Risk criteria.
It is difficult to identify what does and does not fall within the boundaries of minimal risk research. The TCPS definition of minimal risk itself represents a controversial standard (it is not currently in use as a definition of minimal risk in any other English-speaking country). In these circumstances, rather than apply on a case-by-case basis an open-ended and not clearly defined standard, the CREB has decided to list categories of research that it has identified as sufficiently low risk to undergo a process of Expedited Review. This helps to ensure openness and accountability in ethically reviewing a category of research that is not well-defined and whose limits are controversial. Researchers are invited to propose amendments to the listed categories of minimal risk research qualifying for Expedited Review.
Studies that may meet the criterion for minimal risk include research that is limited to the following sources of data (GN #18.104.22.168 and GN #22.214.171.124) and, as such, may undergo expedited review by the CREB Chair (or designate). See GN #2.1.4 for exceptions.
Consent must be obtained from subjects for the use of data derived from the preceding sources. For further information, see GN 2.1.3.
Studies that are based solely on data that is derived from secondary data sources that were originally obtained for primary purposes other than research or from published research may not require explicit consent from the individuals who were the source of the data. See GN 2.1.3 for further details.
However special conditions apply for the use of data from existing databases or for the use of previously collected pathological or diagnostic specimens. See GN 2.1.3 for further details.
The CREB does not consider a case report to meet the definition of research; this is considered to be a medical/educational activity.* Therefore, UBC and affiliated investigators are not required to obtain CREB approval prior to beginning the activity. However, the CREB expects that a process is in place for ensuring that subjects are aware that the author/investigator plans to report about the case.
Investigators who apply to the CREB prior to preparing a case report for publication, or who have been asked by a journal to provide documentation of REB approval prior to publication of a submitted case report, will generally be given a letter of acknowledgment only, not a certificate of approval. Investigators should inform the CREB if a journal does not accept the CREB's decision.
Note that, as stated in the Submission Criteria for Clinical Research section, the CREB does not under any circumstances review nor acknowledge activities that have already been conducted. Requests for such review to satisfy, for example, publication requirements, will not be entertained.
*A case report for CREB purposes is a retrospective analysis of one or two clinical cases. If more than two cases are involved in the analytical activity, the activity will normally constitute "research" and be subject to standard policy and guidelines on research ethics review.
Ethical review of research that uses permanent stable cell lines in laboratory research (i.e. in vitro) is not required.(24 September 2004)
As of 07 June 2005, the updated CIHR Guidelines for Human Pluripotent Stem Cell Research apply to all new or ongoing human stem cell research that is:
The CIHR Stem Cell Oversight Committee (SCOC) must approve the following types of stem cell research:
CIHR requires that stem cell investigators seek REB approval for their non-clinical research, in addition to approval from the UBC Animal Care Committee (when appropriate) and the UBC Biosafety Committee.
The following types of stem cell research do not require REB or SCOC approval:
For further details regarding CIHR requirements, refer to: CIHR Guidelines for Human Pluripotent Stem Cell Research (updated June 2005).
Stem cell research qualifies for Expedited Review with the exception of any research that concerns 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. See GN 2.1.4 regarding "Minimal Risk Studies That Require Full Board Review".
Complete the question as follows:
126.96.36.199 Circumstances Where Consent Is Required for Minimal Risk Studies
Subject consent IS required for collecting prospective subject data as described above in GN 188.8.131.52 .
For further clarification, consent IS normally required in all situations where researchers prospectively gather data from individuals under a research protocol, even though that data is also collected as part of clinical care and the research is minimal risk. Obtaining consent in these circumstances ensures transparency in the relationship between researchers who are also clinicians and those who are their patients/subjects, and it is normally practicable as well.
CREB does not accept the argument that because prospectively collected
clinical data could be obtained retrospectively from a chart review at a
later date, standards for retrospective research of medical records,
including waiver of consent, should apply. If one adopts as a guiding
presumption that any information that could be gathered retrospectively does
not require consent, then it makes perfect sense not to require consent for
prospectively gathered clinical data that could in principle be gathered
later, retrospectively. However, this presumption is incorrect. The correct
ethical presumption in research is that consent is required for the use in
research of any personal medical information. If one starts with this
presumption, then the implied standard is that consent must be obtained wherever
it is practicable to do so. In prospective research, it is normally
practicable to obtain consent.
Retrospective chart reviews are different. They represent a recognized
exception to this presumption, since research ethics boards have recognized
that it would typically be impracticable, for many reasons, to obtain consent
in those circumstances. But it is not so evidently impracticable for
prospective data gathering, since the subject is actually present during the
data gathering. As well, during the time her/his care and treatment is
administered, the patient is also a known and identifiable subject of
research, and the patient is presumptively entitled to know this (in addition
to knowing that her/his personal information will be used for research purposes).
Finally, researchers know that their patients are also subjects of research
in those circumstances, and they need to disclose this non-clinical
relationship to them. These considerations identify a number of ethically
significant disanalogies with retrospective chart reviews.
184.108.40.206 Circumstances Where Consent Is Not Ethically Required for Minimal Risk Studies (03 Jul 2008)
Subject consent is NOT ethically required for the use of data obtained from previously banked anonymized tissue that is NOT linked to other sources of data. Subject consent is NOT ethically required for the use of data obtained from the following sources and where subjects are not being contacted for any research related purpose:
220.127.116.11 Legal Requirements for Consent (Updated 30 March 2007)
The requirements for seeking consent are subject to federal and provincial privacy laws and investigators are responsible for compliance with these laws that relate to their research. The CREB does not have the authority to authorize any procedure that contravenes these laws, and any CREB approval of a waiver of the ethical requirement to obtain consent for Minimal Risk Studies does not entail a waiver of the investigator’s legal responsibility to comply with the law on consent. See GN #39.7.1 for further detail on the privacy legislation requirements as they pertain to information that must be included in consent forms. (24 September 2004)
Studies that involve the analysis of data obtained from non-UBC investigators working at non-UBC affiliated institutions must also include the consent form used to obtain permission for collection of the data/tissue OR a statement that explains the confidentiality provisions under which consent was initially obtained.
The following types of studies must be submitted for full board review.
2.2 FULL BOARD REVIEW OF NEW APPLICATIONS
All studies that do not meet the criteria described in GN 2.1 must be submitted for full board review.
2.2.1 CREB Meetings
Please refer to the “Committee Meetings” section on the PI and Staff homepage in RISe for up-to-date schedules of deadlines and meeting dates. As outlined in a memo on the CREB website, a cap has been placed on the number of new applications that can be reviewed at a UBC Clinical Research Ethics Board meeting.
Guidance Note #2 References:
#3: Application Fee for Industry-Sponsored Studies (Updated 15 November 2005)
The fee described below covers the submission of the initial request for ethical review, subsequent amendment and renewal applications, as well as the submission of serious and unexpected adverse event reports in the case of clinical trials.
As of August 29, 2003, the fee for ethical review of industry sponsored studies is $3000.00 and applies only to research that receives its funding from an industry sponsor (i.e. pharmaceutical/medical devices company or an agent thereof- also refer to page 2 of the Application Form.
Payment of the required fee must be sent to the CREB for all industry-sponsored research.
It is the responsibility of the PI to ensure that the sponsor is aware of this requirement and to submit the cheque/journal voucher/letter at the time of the submission to the CREB.
The CREB will review the research only if the fee or letter accompanies the application.
3.1 FEE WAIVER CRITERIA
The fee is waived for:
For questions about review fees, please contact the applicable REB below:
3.2 MECHANISM FOR SUBMITTING THE FEE
3.3 REQUIREMENTS FOR FEE REFUND
3.4 OUTSTANDING FEES
For those researchers with outstanding fees owing to the CREB, no new reviews will be undertaken until their accounts are brought into good standing.
#4: Institutions (Updated 30 March 2007)
The letterhead of the subject informed consent documents should correspond to the institution(s) selected in question 4.2. Institutions could include:
UBC – Vancouver Campus
UBC-O – Okanagan Campus
C&W – Children’s and Women’s Health Centre of BC: Any research conducted at Children's and Women's Health Centre of BC must be reviewed by the C&W Peer Review Committee in addition to the REB
BCCA – BC Cancer Agency: Researchers at the BC Cancer Agency should submit their new applications for ethical review to the UBC-BCCA REB for all clinical projects and in the case of behavioural projects to either the UBC-BCCA REB or the UBC Behavioural REB.
VCHA – Vancouver Coastal Health Authority: Any research conducted at a VCHA site must be reviewed by the Vancouver Coastal Health Authority (VCHA) in addition to the REB.
PHC – Providence Health Care: Any research involving human subjects conducted at a Providence Health Care site must be reviewed by Providence Health Care for institutional requirements, in addition to the applicable REB of Record (Refer to the Introduction for details)
· St. Paul’s Hospital
· Holy Family Hospital
· Mount St. Joseph’s Hospital
AC – Arthritis Centre
4.1 RESEARCH CARRIED OUT AT A PROVIDENCE HEATHCARE SITE OR BC CANCER AGENCY SITE
Research only carried out at either a PHC or a BCCA site is under the jurisdiction of their respective research ethics boards.
Refer to the Introduction for details on the review process for research carried out by the same investigator or co-investigators at a PHC or BCCA site and another site under CREB jurisdiction.
#5: Document Identification
The title given in question 1.7 of the application form and the title of the protocol submitted should be the same and correspond to the title of any consent form(s) also submitted. The study period should also be entered on page 2 of the application form.
5.2 EXTENSION/SUB STUDIES
Indicate whether the study is an extension or a sub-study of a primary study. For example, in an extension study, the study period could be extended in order to give subjects the opportunity to undergo an extra regimen of treatment with the experimental drug. A sub-study is a concurrent study on a sub-sample/population of the original study sample/population. The CREB reserve the right to require that a sub study or extension study be submitted as a new application.(24 Jul 2008)
5.3 GRANTS COVERING A SERIES OF STUDIES
In some situations, a single grant is awarded to fund a series of studies in the same topic area or line of research over a period of several years (e.g. one study per year for three years). These studies may be sufficiently different that a full ethical review is required of each study. For these types of studies, include the specific title of the smaller study and following that, the more inclusive title of the grant. This will ensure that the Office of Research Services can release the funds at the appropriate time for each specific study.
#6: Required Documentation (Updated December 2006)
RISe will only accept electronic versions of documents.
It is the responsibility of the PI to notify Sponsors and Department Heads that any document that is submitted to the REB will only be accepted in an electronic version. If a Sponsor is unable to provide an electronic version, the PI must convert the document (by scanning the document, or if you have a computerized fax on your computer for receiving faxes, you can fax the document to yourself and save it to your hard drive and then you will have an electronic version to submit to the REB). RISe can accept various types of electronic formats (Word, Excel, Powerpoint, pdf, tif, jpeg. etc.) as attachments to the online application.
The REB office will NOT check the content of attachments. Applications that are submitted without complete protocols, consent forms and attachments will not be reviewed by the REB and will have to be resubmitted.
Assign a version date to all attached documents on page 9 of the application form. This version date must be included in a footnote on each page of the study documents.
Ensure that the documents are submitted in the correct order.
Information re: Electronic Submissions:
· The security features of RISe will not allow the CREB to attach documents for you.
· The CREB will not accept or convert hardcopy documents for you.
· It is the PI’s responsibility to convert hardcopies into an electronic format or otherwise obtain the electronic version of a document.
· The CREB cannot remove passwords from documents. A sponsor may send documents with password protection. The PI must then remove the password protection before attaching the document in RISe.
· If using a videotape, audiotape, or CD/DVD for the study, a transcript of the content must be submitted as an electronic document and one copy of the videotape, audiotape, or CD/DVD must be forwarded to the CREB office.
Contact the applicable REB below with any questions.
Please note: Adverse and Serious Adverse Event Reporting:
The current method of reporting Adverse and Serious Adverse Events to the REB is outside of the electronic system. For details about Adverse Event Reporting, please refer to the CREB website: http://www.ors.ubc.ca/ethics/clinical/c-forms.htm .
6.1 REQUIREMENT FOR RESEARCH PROTOCOLS FOR ALL STUDIES
6.2 DOCUMENTS REQUIRED FOR ETHICAL REVIEW
Include the description (i.e. the correct title) and the correct reference/version numbers and dates on page 9 of the application form for all submitted documents.
As this information will be included on the Certificate of Approval; check for accuracy against the documents submitted.
6.2.1 Specific Requirements for Clinical Trials
Health Canada requires that all clinical trials, whether industry funded or not, comply with the ICH GCP. The following definitions for protocol, protocol amendments, Investigator's Brochure and informed consent are adopted from the ICH GCP Glossary. All other definitions are consistent with the TCPS.
6.2.2 Specific Requirements for Other Types of Studies (Updated 30 March 2007)
With the exception of Investigator's Brochures, tissue banking consent forms, and peer review reports, the preceding types of documents are required, where relevant, for studies that are not clinical trials.
Guidance Note #6 References:
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7.1 PRINCIPAL INVESTIGATOR'S SIGNATURE
The Principal Investigator (PI) for a study is responsible for adhering to the TCPS and other relevant guidelines, and indicates this by clicking "OK" in the Submit Activity view on the application homepage. Based on security in the RISe system, only the PI listed in question 1.1 on the application has access to this Submit Activity on the application homepage. The PI's signature attests to the following:
By signing below, I certify that I have read this application together with its attachments and that all information provided herein is accurate and complete. If circumstances should arise that materially affect the accuracy and completeness of the information provided, I will immediately report the new information in writing. I will abide by all applicable laws, regulations and international guidelines, and the policies of the UBC CREB regarding the conduct of research in humans [UBC Policy, #87 and #89], including UBC's conflict of interest policy [Policy # 97] and the Tri-Council Policy Statement for Ethical Conduct for Research Involving Human Subjects. (24 September 2004)
7.1.1 Optional Designation of Co-investigators with Signing Authority (updated December 2006)
The PI may designate either one or two co-investigators to act as “co-investigators with full signing authority” to submit Post-Approval Activities (PAAs) to the CREB. Note that this option in RISe will only function AFTER a study has been approved by the CREB. It is important to emphasize that the PI will continue to be entirely responsible for the research study. As such, the PI must ensure that designated co-investigators are totally conversant with all aspects of the study. This option may be particularly helpful in situations where the PI is absent for a short time. However, if a PI is to be away for longer periods (i.e. over one month), the REB would expect to be formally notified of a change in PI.
7.2 DEPARTMENT HEAD'S SIGNATURE
The PI's Department Head must also approve the application by clicking “OK” in the Approval Activity view on the application homepage to indicate that the PI has the qualifications, experience, and facilities to carry out their research. If the PI is a Department Head, the Dean of the Faculty or the Head of Division must sign the form.
7.2.1 Division Heads for the Department of Medicine, Faculty of Medicine are permitted to sign the application forms on behalf of the Head of the Department of Medicine. A Division Head who is also the PI must have the Head of the Department of Medicine sign the application form. (24 September 2004).
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8.1 DESIGNATED CONTACT PERSON
The CREB office will send all Provisos, Acknowledgements, and Certificates of Approval to the contact person listed in question 1.2 in the application, who is then responsible for advising the rest of the study team of the outcome of the review.
A Certificate of Approval is required for research to begin.
The outcome of the first review of the application through either a Full Board or an Expedited Review will be one of the following four decisions: Approval, Proviso, Deferral, or Rejected, which the researcher and primary contact listed on the study will receive in an email from the CREB. The notification of the decision sent to the researcher is consistent with TCPS Article 1.9 and ICH GCP Article 3.3.9. (a) and (b).
a. Approvals (Updated 30 March 2007)
As required by the TCPS, the Certificate of Approval will be issued for a term of one year. The Certificate of Approval expires as follows:
Note that if an application or renewal was deferred after being reviewed by the Full Board and the response to deferral from the PI was submitted back to the Full Board, the expiration date would be 1 year from the last Full Board meeting date at which it was reviewed.
Note that approval of study amendments does not affect the expiry date of the original certificate of approval or annual renewal.
i. Approval - the Certificate of Approval is issued and the research may begin once all institutional requirements have also been met.
ii. Request for Information (previously called Proviso Memo) are issued when only a minor modification to the consent form or a response to a simple question is required. The research may begin upon receipt of the certificate and once all institutional requirements have been met; responses to request for information are expected within 21 days unless otherwise specified
iii. Preliminary Approval (24 September 2004) - Occasionally the situation arises whereby research funds need to be released by the UBC Office of Research Services in order that the investigator can begin preliminary work on a study [e.g. to develop a questionnaire, survey or interview tool]. Investigators may submit their preliminary protocol for ethical review to the CREB. The CREB may decide to provide a preliminary approval with the understanding that any part of the project dealing with human subjects cannot commence until the CREB has formally approved a final protocol and associated documents. If an investigator decides to seek preliminary approval, the preliminary Application for Ethical Review must contain as much detail as possible about the study and a cover letter explaining that preliminary approval is being sought must also be provided.
iv. Annual Re-approval - For details on the annual renewal process refer to the CREB website
Provisos are issued when there are questions or requested changes to the proposal or consent forms that must be addressed by the Principal Investigator before approval is given. The CREB authorizes the Chair to grant approval when the concerns addressed to the investigator in the Notice of Ethical Review (i.e., the provisos) have been responded to satisfactorily.
Based on the documentation provided, the CREB is unable to make a final decision. The decision is deferred until the investigators submit the supplementary information or documentation as specified by the CREB in the Deferral, to the CREB for full board review again. Responses to a deferral notice must be received by the CREB meeting deadlines for full board review. A letter must be attached in the Submit activity view by the PI when the application is submitted to the CREB office, which lists the issues identified in the notice and includes the responses to each. Changes to consent forms must be underlined or in bold text and on the correct institutional letterhead.
According to TCPS Article 1.10 on Reconsideration, "Researchers have the right to request, and Research Ethics Boards have an obligation to provide, reconsideration of decisions affecting a research project."
8.2.1 Timelines for Release of CREB Decisions (Updated 30 March 2007)
Board Review of New Applications
b. Expedited Review of New 'Minimal Risk' Applications
Certificates of Approval are issued on RISe usually within three business days of the Chair's decision. See iii) and iv) for exceptions.
Notices of Ethical Review are issued on RISe usually within one business day of the Chair's decision. See iii) and iv) for exceptions.
When the investigators and the CREB cannot reach agreement on a decision of the Board, the researcher can request the UBC Research Ethics Appeal Board to review the CREB decision. TCPS Article 1.11 (a) on Appeals states: "In cases when researchers and REBs can not reach agreement through discussion and reconsideration, an institution should permit review of an REB decision by an appeal board, provided that the board is within the same institution and its membership and procedures meet the requirements of this Policy. No ad hoc appeal boards are permitted." Requests for appeal should be directed to the Office of the V.P Research. See UBC Policy 89.
Guidance Note #8 References:
#9: Co-Investigators and Students (22 December 2005)
If the research is for a graduate degree or medical resident include that information in question 1.3 of the application form.
All other co-investigators, including students and medical residents, should also be listed in question 1.3 of the application form.
9.3 TCPS TUTORIAL (22 December 2005)
When a research application involves any graduate students or medical residents, it is expected that they have individually completed the online TCPS Tutorial BEFORE the application is submitted to the CREB. The CREB requires that all PIs are familiar with the TCPS and recommends completion of the TCPS Tutorial, especially when the PI supervises or teaches classes for graduate students or medical residents. The tutorial is free and takes up to two hours to complete.
TCPS Certificates do not need to be attached to CREB applications. Copies should be retained by the PI and be available on request.
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10.1 NAME OF FUNDING SOURCE
Include the name of the funding source or sources on page 2 of the application form along with the other required information.
10.1.1 For grant-in-aid support, specify whether the grant-in-aid is for the provision of materials in kind such as drug or device. (24 September 2004)
10.2 CHANGES OR ADDITIONS TO FUNDING SOURCE
Researchers must inform the CREB office of any changes or additions to the funding source(s) using the Post Approval Activity “Amendments to Study”.
See the Post Approval Activity button on the study homepage and the accompanying Guidance Notes on the CREB website for further details.
10.3 RELEASE OF RESEARCH FUNDS
The UBC Office of Research Services can only release the funds for awards/grants when the CREB Certificate of Approval has been updated to reflect the addition or change of a funding agency, should this occur.
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11.1 REQUIREMENTS FOR PEER REVIEW
For research with more than minimal risk, the REB must be satisfied about both the value and the scientific validity of the study. Under some circumstances and depending on the level of risk, the REB may request that a peer review be conducted as a condition of approval.
11.1.1 Exception to Peer Review
Research that poses minimal risk will not usually require peer review.
11.2 INDEPENDENT PEER REVIEW INFORMATION
Peer review is considered independent when experts in the field, who are not affiliated with the institutional department carrying out the study or who are not affiliated with the company sponsoring a clinical drug/device trial, have evaluated the study for its scientific appropriateness.
The REB recognizes that an independent peer review may be either 'internal' or 'external'. The appropriate type of review is dependent on the nature of the study.
Peer reviews conducted by granting agencies or by Health Canada, for investigational drugs or devices, are considered to be acceptable types of 'external' peer review.
Provide a description of any independent peer review conducted and attach a copy of the peer review report, if available. This copy need not exceed two or three pages in length.
11.3 PEER REVIEW CONDUCTED BY AN INDUSTRY SPONSOR
Any review process conducted within a for-profit agency is not considered to be independent. However, describe details of any in-house review processes carried out by industry sponsors.
11.4 PEER REVIEW NOT CONDUCTED
If a peer review has not been conducted, explain why this is the case. Do not use 'not applicable' to complete this Box since there are no categories of research which are automatically exempted from peer review.
Guidance Note #11 Reference:
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12.1 OBTAINING REGULATORY APPROVAL FROM HEALTH CANADA FOR CLINICAL TRIALS
Investigators conducting clinical trials involving either investigational drug(s), device(s), or natural health products formulated for therapeutic purposes OR involving a drug/device/natural health product used for an indication outside those specified in the Health Canada Drug Identification Number, Notice of Compliance or Medical Device Licence must submit the appropriate application for regulatory approval to Health Canada before research can begin.
It is the duty of the PI to be certain that Health Canada has issued a NO OBJECTION LETTER before the study begins enrollment.
The Clinical Trial Application (CTA) for drugs/radiopharmaceuticals/natural health products or the Investigational Testing Authorization (ITA) for devices must be filed with the appropriate directorate within the Health Protection and Food Branch of Health Canada:
12.1.2 Compliance with the Food and Drug Act
All investigators conducting clinical trials must be familiar with the details of the Food and Drug Act Regulations and Regulations Amending the Food and Drug Act Regulations (1024-Clinical Trials) (amended June 2001) (17 July 2003).
C.05.001 of the Regulations empowers the Research Ethics Boards to review, approve and conduct periodic reviews of biomedical research involving human subjects to ensure the protection of their rights, safety and well-being.
Several of the important new regulations are summarized below:
12.1.3 Compliance with the Medical Devices Regulations (24 September 2004)
The Medical Devices Regulations are applied under the authority of the Food and Drug Act and regulate the use of medical devices for investigational purposes. The obligations of the sponsor and qualified investigator are covered under these regulations.
12.1.4 Studies Using Positron-Emitting Radiopharmaceuticals (02 December 2007)
An investigator is free to file a clinical trial application (CTA) to Health Canada for a basic research study if they so choose. However, as Health Canada currently has new regulations under development which will eliminate the CTA requirement, in this interim period Health Canada is allowing these studies to proceed without a CTA, provided the requirements and criteria in their Guidance Document on Factors Considered in the Assessment of the Risks involved in the Use of Positron Emitting Radiopharmaceuticals in Basic Research involving Humans are met. The key point of the guidance is that investigators must self-assess their studies against the criteria listed in Section 2 of the guidance document, which includes:
· Pharmacological dose. The amount of active ingredients or combination of active ingredients within the PER(s) is known not to cause any clinically detectable pharmacological effect in humans.
· Radiation dose. The total radiation dose incurred by a subject, including from multiple administrations of PERs, significant contaminants or impurities, and use of other procedures for the purposes of the study is within the limits herein. Dose calculation takes into account radiation doses from other research studies the subject participated in within the year and the possibility of follow-up studies:
Whole body: Single dose: 20 mSv (2 rem)
· Qualifications of investigators. Each investigator is qualified by training and experience to conduct the proposed research study, and a minimum of one investigator involved in the study is a licensed physician, responsible for the medical safety of the subjects.
· Human research subjects. Each investigator selected the appropriate subjects and obtained their informed consent. Research subjects are at least 18 years of age and legally competent. Each female research subject is, on the basis of a pregnancy test, confirmed as not pregnant. Female subjects must not be lactating.
· Quality of PER(s). The PER(s) used in the research study are fully characterized and meet the required chemical, pharmaceutical, radiochemical, and radionuclidic standards of identity, strength, quality, purity and impurities. The quality of the PERs is reproducible so as to give significance to the research study.
The Principal Investigator, as part of the application to the CREB, should demonstrate that he/she has conducted this self-assessment and that the criteria above are met.
12.1.5 Compliance with the Natural Health Products Regulations (24 September 2004)
The Natural Health Products Regulations Part 4; Clinical Trials Involving Human Subjects (January 2004) regulates the use of natural health products that are formulated specifically for therapeutic purposes. The obligations of the sponsor and qualified investigator are covered under these regulations.
12.2 CREB REQUIREMENTS FOR REGULATORY APPROVAL (24 September 2004)
12.2.1 Industry Sponsored Clinical Trials
Specify the date of the application to Health Canada and the Health Canada control number for all clinical trials on page 7 of the application form. The control number must be submitted once obtained if not available at the time of submission to the CREB.
12.2.2 Investigator-Initiated Clinical Trials
Specify the date of the application to Health Canada on page 7 of the application form. A copy of the Health Canada NO OBJECTION LETTER (NOL) must be submitted to the CREB once obtained.
Publication of the results of clinical trials, whether positive or negative, is of obvious value to society and an ethical obligation of investigators to the subjects who voluntarily participated. In recognition of this ethical obligation the major health journals represented by the International Committee of Medical Journal Editors (ICMJE), now require that all clinical trials initiated after June 2005 be registered at the start. Trials that were not registered at onset will not be considered for publication. Ongoing trials that had started prior to June 2005 had until September 2005 to be registered. The CREB supports this approach to wide publication of clinical trial data.
ICMJE requires registration for all clinical trials as defined by "Any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between the medical intervention and the health outcome". Medical intervention is to be interpreted broadly to include drugs, devices, surgical procedures, behavioural or management studies which have the intent to modify a health outcome. In general all Phase III studies will need to be registered. However, Phase I and some Phase II studies are excluded.
Clinical trials must be registered with a registry that meets the requirements of the ICMJE. At present, the CREB is aware of two such registries: ClinicalTrials.gov, which is run by the US National Library of Medicine, and Controlled-trials.com, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry used by CIHR.
The PI of a clinical trial being done at UBC/affiliated sites is responsible for ensuring that the trial is registered with an acceptable international registry. Ordinarily, multi-centre studies will have been registered by the sponsor so the PI at UBC/affiliated sites need only verify that the trial has been registered by the sponsor and note the registry and registration number on page 7 of the application form. For Phase III trials that are only being done at UBC, the registration must be completed by the UBC PI, who must then update page 7 of the application as appropriate.
The UBC Research Ethics Boards expect that the PI will ensure that the trial is registered and appropriately updated when the trial is complete or results are published.
All ongoing clinical trials should have been registered before September 13th, 2005.
#13: Research Proposal Summary
The Research Proposal Summary should include the following information:
Hypothesis or Aim
Justification for the
Guidance Notes #13 References:
#14: Human Subject Enrolment
This item must be completed. It is acceptable to provide an estimate or a range for the number of subjects if the exact number is not known in advance.
Control subjects are defined by the U.S. Office of Human Research Protections as, "Subject(s) used for comparison who are not given a treatment under study or who do not have a given condition, background, or risk factor that is the object of study. Control conditions may be concurrent (occurring more or less simultaneously with the condition under study) or historical (preceding the condition under study). When the present condition of subjects is compared with their own condition on a prior regimen or treatment, the study is considered historically controlled”.
#15: Inclusion Criteria for Subjects
Provide all inclusion criteria as described in the protocol. Otherwise, indicate how these criteria differ from that in the protocol.
15.2 REQUIREMENTS FOR EQUITABLE SELECTION OF SUBJECTS
The selection of subjects must be considered equitable and should strive to achieve a demographically representative sampling, subsequent to the constraints of the research.
15.2.1 Vulnerable Subjects
Special consideration must be given to the potential for inclusion of vulnerable subjects who are not competent to give a legally or ethically valid consent or who have relatively little social or economic power. The research 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.
18.104.22.168 Legally Incompetent Subjects
The inclusion of legally incompetent subjects must meet the requirement of TCPS Article 2.5c, which states "individuals who are not legally competent shall only be asked to become research subjects when the research does not expose them to more than minimal risks without the potential for direct benefits for them."
Refer to GN #34.1 and the CREB Policy #17 on "Obtaining Assent from Subjects Who Are Legally Incompetent".
Guidance Note #15 References:
#16: Exclusion Criteria for Subjects
Provide all exclusion criteria as described in the protocol. Otherwise, indicate how these criteria differ from that in the protocol.
Ensure that a justification is provided if subjects are excluded on the basis of such attributes as culture, language, religion, race, mental or physical disability, sexual orientation, ethnicity, gender or age.
Guidance Note #17 Reference:
#17 and #18: Identification, Initial Contact and Recruitment of Subjects
17.1 IDENTIFICATION, INITIAL CONTACT AND RECRUITMENT OF SUBJECTS
The CREB requires information on how subjects are identified and initially contacted to participate in a research study. In particular, this information should include a description of:
a. the source (i.e. its original purpose, if relevant) of the contact information;
b. who will collect the contact information;
c. who will make the initial contact with the prospective subject;
d. how the prospective subject will be initially contacted;
e. when the prospective subject will be initially contacted, and;
f. the relationship, if any, of study team members to the subjects (e.g., treating physician, teacher).
In addition, attach copies of any recruitment materials, such as letters, advertisements, flyers, radio or television scripts, or Internet/e-mail messages.
17.1.1 Identifying And Contacting Prospective Subjects From Primary Health Care Provider Records
In some situations, the prospective subject's primary care (i.e. family doctor) physician (or other primary health care provider) holds the subject's personal contact information. In this case, permission to use the contact information must be obtained from the subject by the primary care physician before the Investigator can use the information for recruitment purposes. The primary care physician must either verbally ask the prospective subjects' permission to release their names to the Investigator or distribute an introductory letter describing the study to the prospective subjects, with details on how to contact the Investigator if they are interested in participating.
Note that private practice physicians fall under the provisions of the British Columbia Personal Information Protection Act (PIPA). PIPA: Section 21 regulates the disclosure by physicians of personal information for research or statistical purposes. (24 September 2004)
17.1.2 Identification And Initial Contact Of Prospective Subjects From Personal Data Obtained From Public Bodies (24 September 2004)
22.214.171.124 Information Held By Provincially Regulated Public Bodies
The BC Freedom of Information and Protection of Privacy Act (FIOPPA) applies to public sector institutions. These include health care (e.g. hospitals, the Provincial Health Services Board, and regional health boards), public (e.g. provincial government ministries, Medical Services Commission, Pharmanet, WCB) and educational (e.g. school boards, universities) bodies.
Section 35 of FIOPPA (amended 28 March 2003) limits the uses of information collected by such bodies, such that this information cannot be released by the public body for contact purposes, by stating: "35 - A public body may disclose personal information or may cause personal information in its custody or under its control to be disclosed for a research purpose, including statistical research, only if (a.1) the information is disclosed on condition that it not be used for the purpose of contacting a person to participate in the research."
126.96.36.199 Information Held by Disease Specific Registries
Subjects who have previously consented to be included in a registry for research purposes and this consent included contact for future research studies must first be contacted by mail vis a vis the contact information included in the registry. The letter must explain how their contact information was obtained in addition to the purpose of the contact.
17.1.3 Identification And Initial Contact Of Prospective Subjects Attending Specialized Medical Clinics
In some situations, Investigators who are not acting as health care providers are attached to a hospital department/clinic/medical unit that offers clinical care, and conduct research on the patient populations that attend that particular medical unit. It is acceptable for these Investigators to obtain prospective subject names from the patient lists of their hospital's medical units for initial contact purposes. In this situation, the subjects may be contacted in writing to explain how their personal contact information was obtained, and the Investigator's relationship to the medical unit or hospital.
17.2 INITIAL CONTACT WITH PROSPECTIVE SUBJECTS UNDER THE INVESTIGATOR'S CARE OR AUTHORITY
17.2.1 Ensuring Non-Coercive Contact
Special care needs to be taken during the initial contact when the Investigator is in a fiduciary relationship with prospective research subjects. For example, whenever the relationship between the Investigator and research subject is such that coercion could be perceived to be a factor (e.g., when the Investigator is also providing medical care to a prospective subject, or when the Investigator is also the student's teacher), non-coercive means for inviting participation should be used. A typical example of the latter would be posting notices to invite volunteers from the entire group concerned, for example, in the waiting room of the medical clinic, or for the entire school rather than one particular class.
This leads to the recommendation that a treating physician/care provider not be the person making initial contact with subjects unless this is absolutely necessary.
17.2.2 Direct Initial Contact By Study Nurses
The CREB permits study nurses/co-ordinators who co-ordinate studies out of a specialized medical clinic to make direct initial contact with a prospective subject who is attending that clinic for patient care or for research purposes. The study nurse/co-ordinator must identify him/herself and the relationship to the clinic/medical department at the time of contact with the prospective subject.
17.2.3 Initial Contact By Mail
Prospective subjects under the PI's care may also be contacted by mail via an initial contact letter, which can be followed up by a telephone call within a reasonable length of time. The letter should stipulate who will make the follow-up phone call and when this will occur. The CREB prefers that the follow up telephone contact be made by a study nurse/co-ordinator in order to minimize the possibility of coercion, perceived or otherwise. The PI must sign the initial contact letter unless a compelling reason why someone else should sign is provided.
The PI is invited to become involved in the consent process whenever explanations are required which the person making initial contact cannot provide.
17.2.4 Recruitment of Students from School Populations
School districts vary in their requirements for approaching and involving teachers, staff, or students in research. It is the responsibility of the Investigator to know and comply with these local regulations.
A generally acceptable approach involves contacting the principal of the school in order to obtain permission to contact the teacher directly to obtain his/her assistance to recruit students. This may not be sufficient in all districts.
Include documentation of approval from the school district(s) affected by the proposed research.
17.3 INITIAL CONTACT WITH PROSPECTIVE SUBJECTS WHO PROVIDE PERSONAL DATA TO SPONSORS' CALL CENTRES
Subjects may choose to contact a call centre directly to indicate that they would like to participate in a clinical trial and to provide their contact information. The local study centre, upon receiving this information from the call centre, may contact the prospective subject directly by phone, explaining how their name and phone number was obtained. A description of this procedure must be included on page 7 of the application form along with the script used by the call centre to receive calls and all screening scripts.
The CREB is concerned about how personal information (including contact information) given to central screening agencies is handled by these agencies. Investigators are required to describe the planned disposition of the information by the call centre. For example, the CREB would not permit this information to be provided to the sponsor for possible use in marketing or for contacting patients for reasons unrelated to the research project.
17.4 IDENTIFICATION AND CONTACT OF SUBJECTS BY THIRD PARTIES
The CREB does not permit investigators to ask their subjects to invite other people (e.g., family members) to participate in a proposed research study. While recruitment of subjects by subjects may be methodologically desirable and convenient, it may put the index subject and the people they contact in a variety of potentially uncomfortable and coercive situations and is therefore not permitted. At no time should there be any obligation placed on the subject to recruit subjects for the investigator.
In some situations (with CREB approval) it is permissible for subjects to be asked to provide the investigators with names of other potential subjects (e.g., a sibling who might consider participating as a subject), but no further obligation may be placed on the subject. (24 September 2004)
17.5 RECRUITMENT METHODS AND MATERIALS
Letters used for initial contact purposes may be followed by a telephone call. In this situation, the letter must explain when the telephone call will occur, such that there is a reasonable length of time between receiving the letter of invitation by mail and the follow up telephone call. It is preferred that the initial contact letter be accompanied by the full consent form so potential subjects can be more informed and prepared for the subsequent telephone contact.
17.5.2 Initial Contact By Telephone For Obtaining Consent in Emergency Situations
Any proposal to make initial contact with a potential subject by telephone should include a detailed description of the procedure and provide adequate justification.
17.5.3 Recruitment Materials
188.8.131.52 Exclusion of Remuneration From Recruitment Materials
The CREB feels that it is important that the monetary value of the remuneration for participation not be disclosed at the time of recruitment. This mitigates the possibility of inducing subjects to trade accepting potential risks for financial gain. In addition, a prospective subject may not realize that participation can only occur if they meet the conditions of the study's inclusion and exclusion criteria. The promise of remuneration in the recruitment materials may unintentionally mislead some prospective subjects into thinking that they will automatically be enrolled into the study. Refer to GN #25 for guidance on the acceptable value of the remuneration.
184.108.40.206 Inclusion of Information Relating to Provision of Medical Supplies in Recruitment Materials (24 September 2004)
Recruitment materials may include the information that medical supplies required for the study will be provided free of charge; the value of these supplies must not be included in the material.
220.127.116.11.1 The value of the remuneration should be given in the consent form.
17.6 ALLOWING SUFFICIENT TIME FOR PROSPECTIVE SUBJECTS TO CONSIDER PARTICIPATION
Recruitment must be done in such a way that prospective subjects have adequate time between the time of initial contact to the actual consent phase to consider whether or not they wish to participate. For example, prospective subjects who are attending a clinic for elective or scheduled procedures should not be approached and asked to consent to participate in a study at that time. They may be invited to participate in the study and if interested, given the consent form, which they can return, should they decide to participate.
Guidance Note #17 References:
#18: Recruitment of Normal Subjects
Describe the selection and/or recruitment procedures for normal subjects, if these differ from the above. Attach copies of initial letters of contact and any other recruitment documents.
# 20: Research Procedures
Describe any specific manipulations: type, quantity, and route of administration of drugs and radiation, operations, tests, use of medical devices that are prototypes or altered from those in clinical use, interviews or questionnaires.
Specify precisely which procedures are research-related and how they differ from standard care. This information must be transferred to the consent form in such a way that the subject understands how participating in the research may be different from the treatment normally received with standard care.
20.1.1 Time Requirements
Report the exact time requirements for participation by the subject, including :
20.1.2 Radiation Doses Used for Research Purposes
When using radiation doses that are "indicated for research" and are not for the medical benefit of the subject (medically indicated radiation), refer to the Canadian Nuclear Safety Commission (CNSC) "Guidelines for Research on Human Participants Using Radionuclides" (INFO - 0491).
In any research, use of radiation or radioactive materials with human subjects, the study should be designed to use radiation doses that are as low as reasonably achievable (the "ALARA" principle). Radiation dose guidelines apply to the dose from all radionuclide procedures and all diagnostic radiology (x-ray) procedures related to the research study, together with doses from other research studies in which the subject may be participating or has participated in during the year. Repeated use of the same volunteers for different projects is discouraged.
Provide the following information in your application:
1. The source(s) of radiation exposure, including x-ray exposure;
2. The dosage of any radionuclide in activity units (becquerels or Bq);
3. The radiation dose(s) in millisieverts (mSv) to the whole body. When the major dose administered is to a particular organ or tissue, this dose must be converted to the effective dose in accordance with the guidelines of the International Commission on Radiological Protection (ICRP).
20.1.3 Studies Using Magnetic Resonance Imaging
Include the field strength of the scanners as they relate to the possible occurrence of side effects. Refer to the Informed Consent Form template on the CREB website for suggested wording for studies using MRI or PET scans.
20.1.4 Disclosure of Abnormal Findings From MRI, PET, CT Scans Used For Research Purposes (24 September 2004)
The consent form must specify whether scans will be referred for review by a radiologist (or other similarly qualified individual) if any unusual findings are detected or suspected and whether a report would be sent to the subject’s physician. The consent form should explain that the scans are obtained for research purposes only and are not intended to be diagnostic, if that is the case.
20.1.5 Guidance Note for Use of Positron Emitting Radiopharmaceuticals (PER) in Basic Research (24 Oct 2008)
Any research study involving Positron Emitting Radiopharmaceuticals (PERs) whether basic research or not, must have either the Director of the Triumf Centre, or the Head of Radiopharmaceutical Chemistry listed on the Application as a Co-Investigator or Collaborator.
Pending regulatory amendments to the Food and Drug (FD) Regulations, Health Canada (HC) has indicated that basic research studies using PERs with an established safety profile in humans and that comes within the scope of their guidance document(s) is not considered an enforcement priority and will not require the filing of a clinical trial application (CTA) and HC approval.
Note: Any research that is not basic and that does not fall within the parameters of the HC Guidance is subject to the FD Regulations and requires the filing of a CTA.
Therefore, this guidance note applies to cases where the research is in fact “basic” and where the HC parameters for exemption are met. All other research using PERs will be required to meet HC criteria, and a HC No Objection Letter required.
In research using PERs where there is no CTA and no NOL, the CREB requires researchers to confirm that in their estimation the research is 1) basic human research and 2) that it comes within the defined HC parameters of use.
Therefore, if Positron Emitting Radiopharmaceuticals are being used in your research and you have not filed a CTA and obtained a NOL, please clarify that your study is basic research as defined by HC Guidance Policy POL – 0053:
The Use of Positron Emitting Radiopharmaceuticals (PERs) in Basic Research”, i.e. that it is “an investigation in humans involving a drug with a predefined safety profile, intended to obtain data on pharmacokinetics or metabolism of the drug or to obtain basic data related to normal human biochemistry or physiology, changes caused by aging, disease or treatment interventions and not primarily intended to:
a) discover, verify, or identify the pharmacodynamic effects of the drug;
b) identify any adverse events related to the drug;
c) fulfill any immediate therapeutic or diagnostic purpose, or,
d) assess the safety or efficacy of the drug.
NOTE: “drug: as used in the paragraph above refers to the positron emitting radiopharmaceutical.
Guidance Policy Health Canada, http://www.hc-sc.gc.ca/dhp-mps/compli-conform/info-prod/drugs-drogues/pol_0053_tc-tm-eng.php
Please also clarify that your research study falls within the scope of the Health Canada Guidance Document “Factors considered in the assessment of risks involved in the use of positron emitting radiopharmaceuticals in basic research involving humans” and in particular within the criteria for “pharmacological dose” and “radiation dose” as set out in the Guidance Document, and that the PERs being used have been previously used in humans and are not biologic PERs.
Link to Health Canada Guidance Document, http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/compli-conform/pol_0053_per_compliance-prep_conformite-eng.pdf
20.2 SPECIFICATION OF STOPPING RULES (refer to page 8 of the application form as well)
Specify any stopping rules for stopping the research-related procedures/treatment. Also refer to GN #28.
#22: Time Requirements
Ensure that you also include this information in the consent form and that the amount of time stated is consistent in the application, protocol, recruitment material, and consent form.
#23: Risks (22 December 2005)
The following section provides a classification of relevant risks. Information on risks must be consistent with the information on risks provided in the protocol and Investigator's Brochure (IB)/Product Monograph. If information is not available from the protocol or IB, indicate the source of the risk data provided.
23.1.1 Minimizing Harms
Include an explanation of any strategies put in place to minimize and/or manage the harms for subjects and other affected individuals (e.g., reporting side effects to the investigator, rescue medication, early withdrawal from the study).
18.104.22.168 Studies Where The Interaction With Other Drugs Is Unknown (24 September 2004)
Disclose whether the research necessitates that certain medication or treatments not be administered during the study so subjects can evaluate this in the context of their current health.
22.214.171.124 Studies With Wash-Out Periods or Requirements For Stopping Medication (24 September 2004)
The consent form must explain the symptoms/signs that subjects could experience from being taken off of any medication.
Advice on procedures that must be followed in special cases is included in the following sections.
23.1.2 Risks to Others
When applicable, give a clear statement of potential harms to others (e.g., unborn child, sexual partner, family members).
23.1.3 Risks to Women and Men (24 September 2004)
The risk of any harms to pregnant women, to women who could become pregnant during the course of the research or to men with reproductive capacity must be disclosed in the consent form.
Specific instructions regarding the prevention of pregnancy must be included in the consent form as follows:
23.1.4 Social and Psychological Risks
Note that risks to the subject 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 subjects and other affected individuals.
23.1.5 Risks Requiring Special Counselling
Some studies (e.g. genetic tests) may provide results to subjects, which identify them as belonging to a high-risk group on the basis of the result (e.g. genetic status, biochemical test result). TCPS Article 8.3 specifies that in the case of research involving families and groups in genetic research, the researchers must "reveal potential harms to the REB and outline how such harms will be dealt with as part of the research project." In this regard, TCPS Article 8.4 requires that "genetic researchers and the REB shall ensure that the research protocol makes provision for access to genetic counselling for the subjects, where appropriate."
In addition, the CREB believes that it is the PI's responsibility to ensure that research subjects experience no avoidable harm, such as psychological distress, arising from any knowledge that they could obtain as a result of their participation in any type of research study.
The CREB expects to see evidence of measures taken to ensure that counselling services are made available to research subjects if the study tests could lead to information which would have serious consequences for that individual and/or their family.
126.96.36.199 Risks Related to Testing for Reportable Diseases (24 September 2004)
Pre-test counselling for subjects tested for reportable diseases includes the implications, some of which may be life-altering, of having a positive test. These may include the legal obligation for mandatory reporting by the investigator [Refer to GN #188.8.131.52.1 [e53] ], medication implications for sexual partners as well as the impact of a positive test on a subject's insurance policies.
following websites provide some information on pre-test counseling for HIV
testing that can be applied to Hepatitis B and C as well:
184.108.40.206 Other Harms to Subjects Participating in Genetic Studies
In addition, some genetic studies may provide results to subjects, which identify them as belonging to a high-risk group on the basis of their genetic status. CREB requires that the following information be included in the consent form should this be the case.
23.1.6. Other Risks to Subjects Participating in Genetic Studies
A subject's improvement in health, which could have arisen from taking a study drug, may be harmed if the subject cannot afford the costs of a study drug, should it become commercially available, after the research is completed. Should this be a possibility, the CREB requires that the following information is included in the consent form.
23.1.8 Risks to Children (24 September 2004)
ICH Guidance #E11: Clinical Investigation of Medicinal Products in the Pediatric Population states that “protocols and investigations should be designed specifically for the pediatric population (not simply re-worked from adult protocols”. The CREB requires that the protocol includes measures taken to minimize the distress of children participating as research subjects and that this information be included in the consent/assent form(s).
23.2 QUANTIFICATION OF RISKS TO RESEARCH SUBJECTS (22 December 2005)
23.2.1 Quantify the foreseeable risks of harms (side effects) or inconveniences (discomfort or incapacity) to the subject associated with each procedure (including radiation risks from X-rays), therapy, test, interview, or other aspect of the study.
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.
23.2.2 The CREB requires numerical (usually percentage) quantification of risks wherever possible. Qualitative terms such as "rare", "common", "infrequent" are not acceptable unless quantitative ranges are explicitly attached to them. The use of symbols (e.g., < or >) is not acceptable. Quantifiers such as "more than 5%" are similarly not acceptable since they do little to define the magnitude of risk.
It is generally acceptable to provide a qualitative description of the risks associated with standard blood drawing (venipuncture).
It is helpful to list risks in descending order of frequency and/or group them according to category of risk ( e.g. by magnitude, severity, organ system, etc). See the example of categories provided below.(24 September 2004)
23.2.3 Where no percentages are available, specific discussion about risks encountered in case series/case reports, preclinical studies, or studies involving similar procedures are required. If absolutely no relevant data about harms of the experimental procedures is available (e.g. a Phase I trial), Investigators are required to make their best effort to honestly inform subjects about possible risks of participating in the research, even if they can't be quantified. This quantification can be in the form of "for thirty subjects, five experienced a particular side effect." This information must always be included in the consent form.
23.2.4 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. (24 September 2004)
Guidance Note #23 References:
Specify the benefits to the subjects. If there are no benefits, state this explicitly. If any specific therapeutic benefits cannot be assured, but may be hoped for by the subject, state explicitly that the subject may or may not benefit from participation in the study.
Guidance Note #24 References:
#25: Reimbursement and Remuneration
Voluntary consent must be free of undue influence in the form of inducements. The amount or kind of payment should not be such that the subject will base his/her decision to participate on the potential material rewards.
The TCPS Article 2.4 states, "In research projects where subjects will be compensated, REBs should be sensitive to the possibility of undue inducement for participation, such as payments that would lead subjects to undertake actions that they would not ordinarily accept. REBs should pay attention to issues such as the economic circumstances of those in the pool of prospective subjects, and to the magnitude and probability of harms."
25.1 CREB ASSESSMENT OF PROPOSED REMUNERATION
Where researchers plan to provide remuneration to subjects, the CREB will assess the value of the remuneration on a study-by-study basis. In general, remuneration should not be so substantial as to induce subjects to trade accepting potential risks for financial gain.
25.2 TYPE AND VALUE OF REMUNERATION
For most studies, remuneration that is considered reasonable is within the $25.00 to $100.00 range for participation. Randomly provided monetary remuneration (e.g. via entry into a draw) is considered an acceptable form of remuneration. This does not include reimbursement of any expenses incurred by the subject during participation in the research.
25.2.1 Lotteries and Draws
As an incentive to participate in studies, researchers frequently offer participants a chance at a prize in a draw. If such a draw does not include those who decline to participate, technically it becomes a lottery and is illegal in British Columbia (without a license). You must have a license from the province of British Columbia to run any kind of lottery scheme. This includes draws where the subject pays or "barters" for a chance at a prize by completing some aspect of the research project. Consequently, researchers must ensure that participation in the draw is not contingent on participation in the research, and any subjects who withdraw must also have the opportunity to have their names included in such draws.
The CREB considers the use of draws as an acceptable incentive if the names of those who withdraw from the study are also included in the draw.
25.3 REIMBURSEMENT OF EXPENSES
Include any specific details about the reimbursement of expenses related to transportation and parking and when these will be paid.
25.4 NO REMUNERATION OR REIMBURSEMENT
If the subject will not be paid for participation or reimbursed for expenses, this should be stated in the consent form. (24 September 2004)
25.5 ELIGIBILITY FOR REMUNERATION OR REIMBURSEMENT
Subjects must be eligible for remuneration according to their actual amount/duration of participation with no rewards for completing the study or withholding of “owed” remuneration from those who withdraw. (24 September 2004)
Guidance Note #25 References:
#26: Procedures in Place in the Event of an Emergency (Updated December 2 2007)
For applicable research, the CREB requires that sufficient information to reveal treatment assignment in the event of a medical emergency be held locally and that an emergency contact (24 hours a day, 7 days a week), who can break the code, be identified on the consent form(s).
If the code cannot be held locally, the CREB requires a detailed explanation of how the code can be broken in an emergency and how quickly this can occur.
For applicable research, the emergency contact's name and telephone number must be clearly identified in the consent form.
There are a number of circumstances where research subjects or caregivers may need to be able to access information about a clinical trial on an “emergency” basis. At present, CREB requires that an emergency number be available for most studies (as stated in the consent form template, “A 24-hour, 7-day a week phone number is required for studies that involve subjects in research procedures that involve risks from participation”). At present, this information is only required in the consent form.
While a true 24-hour, 7-day a week access telephone number is optimal; it may not be possible, practical or even realistic for every study. For this reason, access to information/research personnel should be, to some degree, individualized based on the risk associated with the study. In addition, having a telephone number on the consent form may not serve the purpose, as subjects are unlikely to always carry with them a copy of the consent form.
In clinical trials where patients are treated with a drug or device (or other form of treatment), there are a few types of “emergency” information that could be required at some time:
1) unblinding to reveal treatment assignment
2) information about the nature and risks of the particular treatment the subject is or has received
3) access to the principal investigator for advice about the nature and risks associated with a particular treatment
The CREB recommends that all subjects enrolled in a clinical trial 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:
In randomized clinical trials of extended duration, there are likely to be ethical reasons for interim analyses and safety monitoring (e.g. Independent Data Safety Monitoring Boards). TCPS Article 7.2 states, "In combined Phase I/II clinical trials, researchers and REBs shall carefully examine the integrity of the free and informed consent process. Where appropriate, the REB may require an independent monitoring process."
Guidance Note #27 Reference:
#28: Stopping Rules
When relevant, describe any plans for interim data monitoring (e.g. interim analysis) and the specific stopping rules (e.g. thresholds), which will be used to determine whether the research will be allowed to proceed.
#29: Protection of Subject Identity
29.1 USE OF IDENTIFIERS ON RESEARCH-RELATED RECORDS
When it is not possible to anonymize research related records (i.e. anonymity is defined as the removal of all personal identifiers from a subject's records), the use of a unique study code or completely bogus initials is considered acceptable by the CREB. Refer to GN #39.7.1 for the standard wording required in the consent form regarding confidentiality and identifiers.
It is the Investigator's responsibility to ensure the protection of the research subjects' privacy.
29.2 PROCEDURES IN THE EVENT OF A BREACH OF CONFIDENTIALITY (24 September 2004)
In situations where a breach of confidentiality has occurred the CREB requires that the following measures be taken to inform the subject of this breach.
1. The subject must be informed in writing what occurred and that this has created the possibility that others outside of the local research team may learn of their condition and/or participation in the study;
2. The subject should be asked if they wish to continue participation in the study and should sign an acknowledgement indicating their willingness to continue participation; and,
3. The letter to the subject and a letter to the CREB describing this situation and the outcome must be submitted to the CREB for review.
29.3 DOCUMENT RETENTION REQUIREMENTS
Refer to the following sources for information on the document retention responsibilities of Investigators.
29.3.1 Clinical Trials
29.3.2 All Other Types of Research Studies
Regulated databanks may also have specific requirements for records retention, which should be adhered to for studies using data from these sources.
USE OF TISSUE AND/OR DATA OBTAINED FROM TISSUE AND DATA BANKS
29.4.1 Use of tissue or data that has been previously collected must receive authorization from the custodian of that bank or registry for its use, regardless of whether the tissue/data is anonymized. Evidence of this authorization must be submitted with the application to the CREB.
29.4.2 If the tissue/data is not anonymized, evidence that consent was obtained at the time of collection for use of the tissue/data must also be submitted. This may include the original consent form or an assurance from the investigator that appropriate protections were undertaken to ensure confidentiality and privacy.
Guidance Note #29 Reference:
#30: Access to the Data and Data Confidentiality
Include information on what measures are taken to prevent unauthorized access to the research data.
30.2 PROTECTION OF ANONYMITY OF DATA
Include information on the provisions in place to protect the anonymity of data when it is transferred to other study sites outside of the local site (e.g. countries outside of Canada, sites in other parts of Canada).
30.3 LINKABLE DATA/TISSUE OBTAINED FROM DATABANKS OR BIOBANKS (24 September 2004)
Identify who (i.e. data/biobank custodian) has authorized access to the stored data/tissue. Identify who retains the key for linking coded tissue or data to a register of human subjects. Explain who will perform the necessary data linkage. It is preferable if the custodian of the bank holds the key to linking the data and performs the data linkage so that identifying information is not released to investigators.
UBC Policy #85 states, "A factor in many cases of alleged scholarly/scientific misconduct has been the absence of a complete set of verifiable data. The retention by the University of accurately recorded and retrievable results is of utmost importance. Wherever possible, all primary data should be recorded in clear, adequate, original and chronological form. In scientific departments, a record of the primary data must be maintained in the laboratory and cannot be removed. Original data for a given study should be retained in the unit of origin for at least five years after the work is published or otherwise presented (if the form of the data permits this, and if assurances have not been given that data would be destroyed to assure anonymity)".
This means data should be stored for at least 5 years, but it may be retained for a longer period provided that it is stored securely. UBC has no explicit requirement for the shredding of data at the end of this period; however destruction of the data is the best way of ensuring that confidentiality will not be breached. Please note that the responsibility for the security of the data rests with the PI.
30.5 ON-LINE SURVEY COMPANIES (24 Oct 2008)
Researchers planning to use on-line survey companies should acquaint themselves with the relevant laws. In particular, section 30.1 of the BC Freedom of Information and Protection of Privacy Act (FIPPA) which states:
“30.1 A public body must ensure that personal information in its custody or under its control is stored only in Canada and accessed only in Canada, unless one of the following applies:
(a) if the individual the information is about has identified the information and has consented, in the prescribed manner, to it being stored in or accessed from, as applicable, another jurisdiction;
(b) if it is stored in or accessed from another jurisdiction for the purpose of disclosure allowed under this Act.
(c) If it was disclosed under section 33.1 (1) (i.1).”
Further, the Office of the University Counsel has issued a memorandum regarding online surveys, which can be found at the following link: http://www.universitycounsel.ubc.ca/faqs/Online_Surveys.pdf
If you have any questions regarding FIPPA legislation and online surveys please consult the Access & Privacy Manager at the Office of the University Counsel, Christina Ulveteg, at Christina.email@example.com
Ideally, Canadian companies with servers located in
The CREB will consider, on a case by case basis, on-line surveys using companies located outside Canada (e.g. United States, Australia) which involve giving the survey internet address to the potential research subject to access from any computer (i.e. the company’s server may collect the IP address of the subject’s computer) and which do not collect demographic data that could be used to identify the research subject.
The consent form or letter of introduction must indicate the location of the survey company’s server and include a description of any associated limits to confidentiality. An example of a typical statement is,
Guidance Note #30 References:
#31: Uses of Data After Study Completion
Describe any future use of the data beyond the conclusion of this research project (e.g., justification for future studies, publication, etc.) and indicate whether subject consent will be obtained now in the current consent procedure or the subject will be contacted later to obtain consent. Either possibility must be described in the consent form. If consent is to be obtained now, the future use of the data must be described in full in the consent form included with the current application. If consent for future use of the data is to be obtained later, full details, including the consent form, must be submitted to the CREB for review and approval before the research begins.
Refer to the Guidance Notes for Renewal on the CREB website for information required by the CREB once the study is completed.
Guidance Note #31 Reference:
#32: Consent Process (22 December 2005)
The information should include details of the following:
1. Who will approach the subject to obtain consent? [Note that this contact should occur a minimum of 24 hours after initial contact, except in the case of emergency situations; See CREB Policy #2 for emergency telephone consent]
2. Who will inform and take the consent from the subject?
3. What is the relationship of the person obtaining consent to the subject?
32.1 REQUIREMENT FOR WRITTEN CONSENT (24 September 2004)
Consent should in most cases be obtained after a face to face discussion with the subject/legal representative has taken place. See CREB Policy #2 for emergency telephone consent and GN 32.1.1 for exceptions.
Written evidence of the subject’s/legal representative’s informed consent/assent must be obtained and documented before participation in the study begins.
Refer to GN #17.6 re: Allowing Sufficient Time for Prospective Subjects to Consider Participation.
32.1.1 Telephone Consent (When Permitted and Related Use of Mailed/Faxed/E-mailed Consent Forms) (15 Sep 2008)
Obtaining consent by telephone for studies involving questionnaires or interviews is permitted in certain circumstances. Consent forms with an introductory letter may be mailed, faxed, or e-mailed to potential subjects in these studies. The CREB expects that the consent interview will occur at a reasonable time after the consent form has been sent. See GN 220.127.116.11 for details.
Obtaining consent by telephone from authorized third parties is permitted in emergency situations. See CREB Policy #2 for details.
The CREB will consider obtaining consent from research subjects by telephone in other special circumstances if a justification is given.
18.104.22.168 Questionnaires/Interviews Conducted by Telephone (24 September 2004)
Consent forms with an introductory letter (indicating that a follow up phone call will be made) may be mailed or faxed to prospective subjects when the study involves questionnaires/interviews that must be conducted by telephone. A follow up telephone call can then be made after a reasonable period of time to the subject to obtain their verbal consent in order to proceed with the interview or questionnaire. The complete written consent form should be read to subjects over the phone and their verbal consent documented prior to proceeding with the interview/questionnaire. The subject’s signed written consent form must be returned to the investigator as evidence that written consent has been obtained. The investigators must maintain a verifiable record detailing when and by whom verbal consent was obtained by phone.
The principal investigator or designate will sign the consent form after receiving it from the subject.
NB This does not change the content of our guidance notes except to add that the CREB will consider granting consent by telephone in other special circumstances besides emergencies and telephone interviews. (15 Sep 2008)
[n.b. This guidance pertains to studies of a clinical nature only; studies which are of a behavioural nature and which use questionnaires and interviews only for collecting data must be referred to the Behavioural Research Ethics Board.]
22.214.171.124 Studies Using Questionnaires Only (24 September 2004)
The returned questionnaire may be taken as evidence of implied consent. Note that the questionnaire should only be identified by subject ID number. Refer to GN #39.2.1
[n.b. This guidance pertains to studies of a clinical nature only; studies which are of a behavioural nature and which use questionnaires and interviews only for collecting data must be referred to the Behavioural Research Ethics Board.]
Guidance Note #32 References:
· ICH GCP Section 4.8.8
#34: Competency: Research Involving Subjects with Questionable Capacity to Consent
This section is intended to provide guidance on the requirements for obtaining consent or assent for research involving subjects who would not be considered legally competent to give their own consent.
The determination of legal competence is the responsibility of the PI or designated representative. Competency must be assessed not only at the time of obtaining initial consent but also must be assessed on an ongoing basis throughout the duration of the study. Should a legal authorized representative of the subject consent on behalf of a subject, the PI or delegated representative is also obligated to assess that representative’s competence to consent.
Types of subjects who may fall into this category include: (24 September 2004)
· individuals with permanent or transient cognitive impairments (e.g. subjects with Alzheimer’s Disease, subjects who are sedated/ventilated subjects with a variable/permanent mental illness);
· children who do not yet meet the tests for competency.
34.1 SUBSTITUTE DECISION MAKERS (24 September 2004)
The British Columbia Health Care (Consent) and Care Facility (Admission) Act (1996): Part 2, Section 16 lists individuals who may qualify as a temporary substitute decision maker. Note that the Public Guardian and Trustee may be the legal representative for some subjects.
TCPS Article 2.5 states, "Subject to applicable legal requirements, individuals who are not legally competent shall only be asked to become research subjects when:
a. The research question can only be addressed using individuals within the identified group(s);
b. Free and informed consent will be sought from their authorized representative(s); or
c. The research does not expose them to more than minimal risks, without the potential for direct benefits to them."
TCPS Article 2.6 specifies the following minimum conditions that must be met for research involving incompetent subjects:
a. "The researcher shall show how the free and informed consent will be sought from the authorized third party, and how the subject's best interests will be protected.
b. The authorized third party may not be the researcher or any other member of the research team.
c. The continued free and informed consent of an appropriately authorized third party will be required to continue the participation of a legally incompetent subject in research, so long as the subject remains incompetent.
d. When a subject who was entered into a research project through third-party authorization becomes competent during the project, his or her informed consent shall be sought as a condition of continuing participation."
TCPS Section 2E states that competence (capacity to consent) consists in "the ability of prospective subjects to give informed consent in accord with their own fundamental values. It involves the ability to understand and to appreciate the potential consequences of a decision..." (emphasis added). There are thus two thresholds or tests that must be met to establish capacity to consent: capacity to understand, and capacity to appreciate, one's decision.
· Understanding is the ability to discern in significant measure the nature of the research and the consequences of choosing/forgoing participation in it.
· Appreciation is the ability to give reasons for participation that reflect, or are consistent with, the prospective subject's own fundamental values. It assumes adequately developed adult capacities for forming and revising personal values.
must judge the potential subject's ability to consent to research on his or
her own behalf, in all patients, in all research projects, regardless of the
prospective subject's age. Although BC health care legislation appears to use
only an "understanding" test for determining capacity to consent,
case law and health care practice take a broad interpretation of
understanding to include "appreciation". Thus, the TCPS distinction
between capacity to consent and capacity to assent is applicable in BC.
34.2 OBTAINING ASSENT FROM LEGALLY INCOMPETENT SUBJECTS, INCLUDING CHILDREN AND THE MENTALLY IMPAIRED
According to TCPS, legally incompetent subjects may be ineligible to participate in research unless they assent to participation. Refer to GN #36 for discussion of the CREB assent policy and a full description of the assent requirement and procedures, including preparation of assent forms required by the CREB.
The procedures that the researcher plans to adopt for obtaining assent must be described on page 6 of the application form.
Guidance Note #34 References:
#36: Assent (Updated 30 September 2005)
The procedures the researcher adopts for obtaining assent to participate in research from certain legally incompetent individuals must be described on page 6 of the application form.
Please see the CREB Assent Form Template on the CREB website.
This guidance note describes procedures for obtaining assent. It also aims to answer questions about what constitutes assent, how to assess when subjects are capable of assent, how assent differs from consent, and why seeking assent from certain prospective subjects is ethically important. These questions raise ethical and legal issues that require systematic discussion. Researchers must be informed about these issues. Those who already have a grasp of them or who wish to begin by reviewing the procedures for obtaining assent may skip to GN #36.6. A summary of procedures is included in GN #36.8.
36.1 CREB POLICY ON ASSENT
The CREB requires researchers to ascertain the willingness of individuals to participate in the research if they are legally incompetent but can nevertheless understand the nature and consequences of the research. These individuals will normally be required to assent by verbal or physical means or to sign an assent form before they can participate in research. These requirements may apply even though free and informed consent has been obtained, or is available, from an authorized third party.
36.2 TRI-COUNCIL POLICY ON ASSENT
The CREB assent policy follows the Tri-Council requirements for obtaining assent, which state: "Where free and informed consent has been obtained from an authorized third party, and in those circumstances where the legally incompetent individual understands the nature and consequences of the research, the researcher shall seek to ascertain the wishes of the individual concerning participation. The potential subject's dissent will preclude his or her participation." (TCPS Article 2.7)
The Tri-Council further explains the meaning and scope of this Article as follows: "Many individuals who are not legally competent are still able to express their wishes in a meaningful way. Prospective subjects may thus be capable of verbally or physically assenting to, or dissenting from, participation in research. Those who may be capable of assent or dissent include: (a) those whose competence is in the process of development, such as children whose capacity for judgment and self direction is maturing; (b) those who once were capable of making an informed decision about informed consent, but whose competence is now considerably, but not completely, diminished, such as individuals with early Alzheimer's disease; and (c) Those whose competence remains only partially developed, such as those suffering from permanent cognitive impairment." (TCPS Article 2.7)
TCPS Article 2.7 requires researchers to determine the willingness to participate in research of prospective subjects who are legally incompetent but who are nevertheless capable of understanding the nature and consequences of the research. The dissent of these prospective subjects, by verbal or physical means, precludes their participation in the research. Furthermore, their participation is precluded even though free and informed consent has been obtained, or is available, from an authorized third party. Such a policy recognizes that (1) subjects with diminished competence retain some control over decision-making, and that it is appropriate to protect their dignity in this respect; (2) it is important to preserve relations of trust between subjects and health care providers; and (3) the voluntariness of health care research must be protected to preserve public trust in it and in health care generally.
For the same reasons, TCPS also clearly contemplates seeking assent from legally incompetent individuals who are capable of understanding the nature and consequences of the research (see the passages from TCPS Article 2.7 quoted above). However, these passages and TCPS Article 2.7 fall short of requiring the explicit assent of all such prospective subjects as a condition of their participation in research. The CREB interprets this to mean that failure to assent should not necessarily be construed as dissent, and thus does not always preclude participation in research.
Thus, there are three classes of individuals who must be considered among the legally incompetent who are capable of assent: those who express assent, those who express dissent, and those who express neither. The status of the first two classes is straightforward regarding participation in research: assenting individuals may participate in research with the informed consent of an authorized third party; dissenting individuals may not. Explicit direction with the third class is not given by TCPS, but it is evident that such a group exists and has a morally separate status from the other groups. For example, researchers may at least occasionally encounter an 11 year old who is legally incompetent and who understands the nature and consequences of participation in research, but who remains ambivalent regarding participation in research and does not clearly assent or dissent. Such a prospective subject may also appear to rely mainly on parents or a guardian to make a decision for him or her, and this may be appropriate in the circumstances. A policy on assent must identify procedures with respect to each of these classes of individuals.
36.3 CREB INTERPRETATION OF TCPS ASSENT POLICY
The CREB interprets TCPS policy as requiring that:
i. assent is normally required of prospective subjects who are not legally competent but who can understand the nature and consequences of the research. Prospective subjects who provide such assent, by verbal or physical means, may participate in research, subject to obtaining free and informed consent from an authorized third party (and subject to other TCPS requirements governing the participation of legally incompetent subjects - see TCPS Articles 2.5 and 2.6).
ii. prospective subjects who are not legally competent but who can understand the nature and consequences of research and who communicate unwillingness to participate in research by verbal or physical means (i.e., who dissent) are precluded from participation, even though free and informed consent has been obtained, or is available, from an authorized third party.
iii. prospective subjects who are not legally competent but who can understand the nature and consequences of research and who neither clearly assent nor dissent must be handled with caution and careful judgment must be exercised on a case-by-case basis by researchers when deciding to include these individuals in research. Authorized third party consent is required as a condition of their participation in research.
The CREB does not accept the suggestion in the TCPS discussion of assent quoted above that early Alzheimer patients are never competent to consent to participate in research.
GN #36.4 and GN #36.5 explain how to identify capacity to assent and procedures for obtaining assent from prospective subjects. GN #36.6 lists considerations for handling prospective subjects who are technically capable of assent but who neither assent to, nor dissent from, participation in research.
36.4 CAPACITY TO ASSENT CONTRASTED WITH CAPACITY TO CONSENT
TCPS states that competence (capacity to consent) consists in "the ability of prospective subjects to give informed consent in accord with their own fundamental values. It involves the ability to understand and to appreciate the potential consequences of a decision..." (TCPS Section 2E, emphasis added). There are thus two thresholds or tests that must be met to establish capacity to consent: capacity to understand, and capacity to appreciate, one's decision. Understanding is the ability to discern in significant measure the nature of the research and the consequences of choosing/forgoing participation in it. Appreciation is the ability to give reasons for participation that reflect, or are consistent with, the prospective subject's own fundamental values. It assumes adequately developed adult capacities for forming and revising personal values.
By contrast, capacity to assent is present if the prospective subject has not adequately developed, or has lost, an adult capacity for appreciation but nevertheless has the capacity to understand the nature and consequences of the research. Examples include prospective subjects who can in significant measure understand the nature of the research and the potential consequences for them of participation but who, because of lack of maturity or cognitive impairment, do not have settled personal values, are unable to develop them, or are unable to give reasons that reflect their settled values. Assent must be sought from these prospective subjects for the reasons given in GN #36.3. Their dissent precludes their participation. Assent/dissent can be given by verbal or physical means.
Although BC health care legislation appears to use only an understanding test for determining capacity to consent, case law and health care practice take a broad interpretation of understanding to include appreciation. Thus, the TCPS distinction between capacity to consent and capacity to assent is applicable in BC.
36.5 CONSENT AND ASSENT IN RESEARCH WITH CHILDREN (Updated 13 July 2004)
36.5.1 Research in a child's best interests (i.e., with a potential health benefit)
Children (18 and under) may be legally capable of consenting to participate in research if certain conditions are met under the Infants Act. Under that Act, children are apparently legally able to consent to participate in research if they are competent and if participation is "in their best interests". The tests for competence given in the previous GN must be applied to determine their capacity to consent. Children who have the legal capacity to consent must sign the consent form in order to participate in research, and their assent is therefore unnecessary.
In all cases where a child is legally competent to consent to participate in research, parental consent cannot be sought on behalf of the child. However, the CREB may permit researchers to make parental agreement an inclusion condition for the competent child's participation in the research, particularly if parental support is required to assist the child's participation (e.g., transportation, assisting/overseeing taking of therapy, etc.).
36.5.2 Research not in a child's best interests (i.e., with no potential health benefit)
126.96.36.199 Where the risk is more than minimal
Where participation in the research is not in the child's best interests, it would appear that the child cannot be legally competent to give consent, and consent must be sought from an authorized party until the child is 19 years old. However, wherever a legally incompetent child has the capacity to assent, the assent policy described in this appendix must be observed.
188.8.131.52 Where there is minimal risk
If a child
is competent according to the tests described in GN
#36.4 and if s/he is a prospective subject in research that offers no
benefit but poses minimal risk, the CREB takes an "ethics first"
position that s/he is competent to consent to participate in the research.
The CREB takes this position because (1) the best interests of the child are
unlikely to be undermined by such participation; and (2) competent people are
normally thought to be entitled to make their own decisions, to be the best
judges of what is in their own best interest and should be presumed to have
their own reasons for participation in research even if there is no potential
benefit to them. Hence, the CREB believes that competent children in these
situations should be permitted to judge for themselves whether they will
participate in this type of research by consenting on their own behalf.
36.6 PROCEDURES FOR OBTAINING ASSENT
Researchers must determine the willingness to participate in research of prospective subjects who are legally incompetent but who have the capacity to assent. This must always involve a face-to-face interview and dialogue between the prospective subject and the principal investigator or his or her delegate. This interview must convey the main information contained in the consent form using concepts and terms that are developmentally and cognitively appropriate. In many circumstances, it will be appropriate to supplement this discussion by giving a prospective subject a written assent form to review. This Guidance Note includes guidelines and procedures for preparing assent forms. These also serve as a checklist for information that is to be conveyed verbally to prospective assenting subjects, including those who cannot meaningfully review a written assent form.
A template for preparing the assent form is available on the CREB website.
These assent guidelines and procedures are in addition to the procedures for obtaining informed consent. As discussed above, authorized third party consent is a condition of permitting an assenting legally incompetent person's participation in research.
36.6.1 Preparation of Assent Forms
Preparation of a separate written assent form will often be required for legally incompetent prospective subjects who are able to review information in this medium. An assent form is recommended for children aged 7-13. An assent form is not normally required for legally incompetent minors who are aged 14-18, since they will usually be cognitively mature enough to read the consent form. A separate procedure for this group is described below. An assent form is not normally required for children under the age of 7 who have the capacity to assent.
An assent form must not be merely a bureaucratic device but must be part of a meaningful process of seeking assent that describes the aims and procedures of the research using concepts and terms that are developmentally and cognitively appropriate. It should explain the research in such a manner that a prospective subject can provide meaningful assent. This must include, in language that the prospective subject can understand:
a. a description of the purpose of the research. a description of the research procedures and the potential risks, discomforts, and hoped for benefits of participation, including possible benefits to others. The CREB recognizes that it will often be appropriate to give this information summarily and with less precision than is normally found in a consent form. Nevertheless, the information should not be so scant that subjects are surprised by aspects or consequences of their participation.
b. a statement of the amount of time that participation in the study will take.
c. a statement that the subject's confidentiality will be respected (e.g. that the subject's involvement will be kept private and that everyone who is connected with the study is required not to reveal the subject's name or involvement in the study to others.)
d. statements that participation is voluntary, that the subject may refuse to participate at any time without giving reasons, that no one connected with the study will be angry if a decision to leave the study is made after giving assent, and that all other health care will remain available.
e. statements that the prospective subject has had the opportunity to ask questions, is encouraged to discuss his or her participation with relatives (parents or guardians for children) or friends, and that all questions have been answered.
f. a statement that questions are encouraged and may be asked at any time.
g. a place for the prospective subject to sign and date his or her assent. (The principal investigator, witness, and authorized third party are not required to sign the assent form. There will be an assent statement in the consent form that eliminates the need for this. See GN #36.6.5).
Phrases such as "will you help me?" or "we would like your help with this" are not permitted in an assent form since children are unlikely to refuse. It is best simply to ask the child if he or she would like to participate.
Prospective subjects who dissent from participation must not be required to sign any document stating that they refuse to participate in research.
The assent form should be as brief as reasonably possible, and no longer than two pages using at least a 12-point font. Merely technical information, such as the name of the sponsor, disclosure of an investigator's financial interests, advice that legal rights are not limited by participating, etc., can typically be omitted. The subject must receive a copy of the assent form and have had adequate time to review it and to discuss it with relatives or friends and the principal investigator (or delegate) prior to assenting.
36.6.2 Special Requirements for Preparing Assent Forms for Children Aged 7 - 13
When preparing assent forms for children it is especially important to convey information that is sensitive to their perspectives on the procedures, risks, discomforts, and inconveniences that they will encounter. For example, it may be appropriate to explain to children what they will experience simply by being in a hospital (for example, that they will be in a room with other children, that they will have to spend most of their time in a hospital bed and will not be able to get up and walk around without immediate supervision or that they will be able to walk around unsupervised, that their parents will not be able to be with them all the time, that they will spend a certain number of nights away from home, that they will be looked after by nurses and doctors, etc). Also, it will typically be appropriate to describe how the research procedures will change how they feel or look (for example, that a medication will make them dizzy or itchy, or that they will be connected by tubes to a machine, or that they will have a scar and what it will look like).
36.6.3 Obtaining Assent from Children Under 7 Years of Age
Children who are under 7 years old and who are capable of assent will not normally be capable of reviewing an assent form. However, the guidelines described in GN #36.6.1 and GN #36.6.2 should be observed in seeking their assent.
Obtaining Assent from Legally Incompetent Subjects Aged 14 and Above
Consent forms are supposed to be written for approximately a grade 7 level of reading comprehension. In practice, this is often optimistic. However, many prospective incompetent subjects who are 14 years and older should not have difficulty reading the consents that are prepared for competent subjects to sign. Where this is the case, it is not necessary to provide a written assent. A separate page where the legally incompetent subject can sign and date his or her assent is required to be added to the consent form. The signature should appear beneath the following text:
SUBJECT'S ASSENT TO PARTICIPATE IN RESEARCH
I have had the opportunity to read this consent form, to ask questions about my participation in this research, and to discuss my participation with my parents/guardians.** All my questions have been answered. I understand that I may withdraw from this research at any time, and that this will not interfere with the availability to me of other health care. I have received a copy of this consent form. I assent to participate in this study.
(**Substitute appropriate wording if the subject is 19 or older.)
The CREB does not require this statement to be signed by the authorized third party, a witness, and the principal investigator or delegate, since they must sign the consent form as a condition of the legally incompetent assenting subject's participation in research, and the consent form will contain an acknowledgement that the subject assents.
36.6.5 Assent Statement in Consent Forms Signed by an Authorized Third Party (e.g., Parent or Guardian)
The following paragraph is required to appear in the consent form in cases where the subject assents to participate in the research:
The parent(s)/guardian(s)** and the investigator are satisfied that the information contained in this consent form was explained to the child** to the extent that he/she is able to understand it, that all questions have been answered, and that the child** assents to participating in the research.
(**Substitute appropriate wording if the research subject is not a child.)
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 subject/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 subject may also be appropriate and is not precluded by the addition of this statement to the consent form.
36.7 PROSPECTIVE SUBJECTS CAPABLE OF ASSENT BUT WHO NEITHER ASSENT NOR DISSENT
The CREB recognizes that in some circumstances prospective subjects may technically have the capacity to assent, but they may not clearly express a preference in favour of, or against, participating in the research after the procedures described in GN #36.6 have been administered. Such prospective subjects should not automatically be precluded from participation, but caution and special care must be exercised to ensure that there are sufficient grounds to include these participants in the research. Some guidelines include:
a. an attempt must be made to determine what the subject would have chosen when he or she was competent (if relevant). If the subject when competent would have dissented, this is sufficient to preclude participation.
b. consideration of what is in the subject's best interests.
c. consideration of the degree of risk and prospect of benefit from participation for the prospective subject.
d. consideration of whether the intervention involved in the research holds a prospect of an important benefit to the health or well-being of the subject and is only available in the context of the research.
e. authorized third party consent is required in all such cases, as per TCPS Articles 2.5, 2.6 and 2.7.
f. where the subject clearly expresses his or her dissent after being included in the research, this must be respected. The subject must be informed of this continuing right to dissent as soon as possible after a decision is made to include him or her in the research.
g. where the prospective subject is included in the research, the principal investigator or his or her delegate shall document the assent procedures that were followed, the prospective subject's responses, and the rationale for including the subject in the research.
h. prospective subjects shall not be required to sign any document stating that they do not assent or dissent.
i. the assent statement referred to in GN #36.6.4 shall be struck from the consent form, if it is previously included there, where these individuals are included in the research.
36.8 SUMMARY OF PROCEDURES FOR OBTAINING ASSENT
A reminder: This table summarizes procedures for obtaining assent from different classes of legally incompetent subjects. It is based on standard, but defensible, presumptions about age-related levels of cognitive ability and development. As such, the table cannot be followed rigidly. It may be appropriate, for example, to provide a written assent for prospective subjects over the age of 14 who lack the cognitive ability to meaningful review a consent form (for example, certain mentally impaired persons); or there may be cases where a prospective subject between 7 and 13 years old, or over the age of 14, is incapable of meaningfully reviewing an assent form (for example, illiterate or mentally impaired persons); or there may be the rare case of a 6 year old who can meaningfully review an assent form. In all instances, the assent procedures to be followed are determined by the prospective subject's level of cognitive development and ability.
Guidance Note #36 References:
[BACK TO TABLE OF CONTENTS]
The CREB believes that the consenting process is continual and requires vigilance on the part of the PI to ensure that information that may in any way alter a subject's decision to remain in the study be conveyed in a timely manner to that subject. Information that may affect the subject’s safety may be relayed to the subject verbally as quickly as possible (refer to GN #37.3 below).
should be made to ensure that any new information which has the potential to
change a subject’s decision to continue participation is conveyed in written
form to the subject. The information may take the form of a letter or an
addendum to the consent form unless it is more appropriate to administer the
revised consent owing either to the special circumstances of the subject or
to the importance of the new information.
Verbal confirmation of a subject's decision to continue participating may be obtained if informed by letter or verbally and should be documented accordingly. The subject should be given a copy of the consent as part of the process for deciding whether or not to continue participation in the study. Revised consents, addendums or letters must be submitted to the CREB for approval prior to their use unless another prior arrangement is made with the CREB.(24 September 2004)
The following sections provide information on provisions required in special cases.
37.1 INCOMPETENT SUBJECTS WHO BECOME COMPETENT
The informed consent of a subject who was incompetent at the time of enrolment but who becomes competent during the project should be sought as a condition of continuing participation. This means that although subjects who were incompetent cannot give consent to receive the experimental intervention(s) after they have been administered, that the subject must consent to continue participating in the study (i.e. consent to receive any remaining procedures). Refer to GN #39.
37.2 COMPETENT SUBJECTS WHO BECOME INCOMPETENT
In situations where a subject becomes incompetent during a study, and where the investigator intends to continue to include the subject in the research, the PI is obliged to find an appropriate third party who will agree to monitor consent accordingly on behalf of the subject, as long as the subject remains incompetent. If a third party does not exist, the best approach is to consult the CREB for guidance.
In addition, refer to the CREB policy #17: Obtaining Assent from Subjects who are Legally Incompetent, as this may be relevant for some subjects who become incompetent during the study and who will need to assent to the study, if they are capable of doing so.
37.3 NEW INFORMATION ABOUT RISKS (24 Oct 2008)
When previously unknown/undisclosed risks of research become available, investigators are required to inform all subjects/legal representatives, to whom this information may be relevant using appropriate means within an appropriate time, depending on the nature and consequences of the risk. This may involve :
1. informing the subject(s) verbally of additional risks or changes in procedures and ensuring that the communication of this information is documented in the study notes of the investigator and;
2. informing subjects who have completed their study treatment if the newly identified risks could still affect them (e.g. irreversible or delayed adverse effects).
reconsent is required in situations when the information concerning risks has
the potential to affect the subject's decision to continue participation in
4.8.2 states that " the written informed consent form and any other
written information to be provided to subjects should be revised whenever
important new information becomes available that may be relevant to the
Any new risks or clarification of risks disclosed to subjects would
have to be disclosed to the CREB in writing as amending the
application/protocol, and in most cases the consent form. In cases where the new information about
risks adds substantially to the knowledge of the risks borne by subjects, the
CREB require clear documentation of disclosure.
Guidance Note #37 References:
· TCPS Article 2.6d re: incompetent subjects who become competent
· ICH GCP Sections 4.8.2 and 4.8.11
#38: Provisions for Obtaining Consent from Subjects who Require Special Assistance
The PI is responsible for ensuring that for "English as a second language" (ESL) subjects, either a consent form in the most appropriate language or an appropriate translator is present during the initial informed consent process.
38.2 TRANSLATED CONSENT FORMS
Guidance Note #38 Reference:
#39: CONSENT FORMS (22 December 2005)
Refer to the CREB consent form template on the CREB website for detailed information on consent form requirements. Note that, in most cases, consent forms should be written at a grade 7 level of understanding.
39.2 EXCEPTIONS TO THE REQUIREMENT TO OBTAIN INFORMED CONSENT (03 Jul 2008)
Studies that do not require informed consent include those whose data is derived solely from:
a. secondary data obtained from medical records (i.e. chart reviews),
b. previously anonymized tissue (i.e., there is no way to link the tissue to the subject) from tissue banks
c. tissue previously collected for clinical purposes that is no longer needed for any clinical purpose and that has been anonymized (i.e., there is no way to link the tissue to the subject) ,and there is no potential for harm to subject; or.
d. anonymous questionnaires (i.e., where there is no way to link subjects to the questionnaire responses). No formal consent form is required for such questionnaires, although the CREB will require a letter of invitation describing the goals of the study, the confidentiality protections that that are in place, and other CREB requirements regarding questionnaires.
TCPS Article 10.3b states "When collected tissue has been provided by persons who are not individually identifiable (anonymous and anonymized tissue), and when there are no potential harms to them, there is no need to seek donors' permission to use their tissue for research purposes, unless applicable law so requires."
questionnaires completed by subjects and returned to the researcher can be
taken as implied consent. However the introductory letter/consent form must
state this explicitly (e.g. 'If
you wish to participate in this research study and are comfortable with the
procedures described in this letter/form, please complete the attached
questionnaire and mail it back to us').
39.2.2 Special CREB Authorization
One other exception to this requirement applies in situations where the CREB can, under very specific circumstances, give special authorization to proceed with a study without subjects' consent where they are incapable of providing it, and where guardians or others may not be able to consent on their behalf for various reasons. Refer to TCPS Article 2.5.
Investigators do however still have obligations to inform these subjects about the nature of the study and their participation in it if they become competent to receive that information. The subject shall be informed that the initial investigation had prior CREB approval. (24 September 2004)
In the event that the subject can participate in remaining part(s) of the study, a consent for the remaining part(s) of the study should be prepared that informs subjects who did not consent to the initial investigation of what happened and why they are now being requested to continue to participate. The consent form shall explain that the initial investigation had prior CREB approval.(24 September 2004)
39.3 TIMING OF CONSENT
The CREB considers the consent to be valid as of the giving of it by the subject, i.e. the time it was signed or verbally provided, unless a protocol stipulates that the consent is not valid until such time as the PI or designate signs the form.
The CREB does not recognize consents that are obtained "after the fact".
39.4 PARTICIPATION IN SUB-STUDIES
The consent form for the main study must include a provision that allows the subject to decline participating in a sub-study, should the sub-study already be planned.
39.5 PARTICIPATION IN OPEN LABEL EXTENSION STUDIES
If a study protocol includes a provision/plan for an open-label extension study, the main consent form should mention that the subject might be offered an opportunity to participate in another longer-term study after this initial study is finished.
An entirely separate informed consent process must be administered at the time of enrolment into the extension study, using a specific consent form dedicated to the extension study.
When necessary, the consent form for the open-label extension study may be submitted as an amendment. For further details, refer to the Guidance Notes for submitting amendments on the CREB website.
39.6 SPECIFIC CONSENT FORM REQUIREMENTS
39.6.1 Tissue Banking Studies
The following TCPS requirements must be observed for obtaining free and informed consent for the purposes of banking tissue (including blood).
the collection and use of human tissues for research purposes shall be
undertaken with the free and informed consent of competent donors.
c. In the case of deceased donors, free and informed consent shall be expressed in a prior directive or through the exercise of free and informed consent by an authorized third party.
d. When identification is possible, researchers shall seek to obtain free and informed consent from individuals, or from their authorized third parties, for the use of their previously collected tissue.
The following CREB policies must be applied if relevant:
184.108.40.206. Mandatory Tissue Banking
220.127.116.11 Donation of Tissue For Unspecified Uses
18.104.22.168 Information Details Required In Consent Forms For Tissue/DNA Banking Purposes
The information described below must be included in either the subject consent form for the entire study, if tissue/DNA banking is part of the study, OR in a separate consent form, if consent to bank tissue/DNA is being requested in connection with a research study but is independent of the subject's participation in that study. Include the following information in the tissue/DNA banking consent form:
a. The research purpose, and the specific uses of the tissue;
b. The type and amount of tissue to be taken, as well as the location(s) where the tissue is to be taken;
c. The manner in which tissue will be taken, the safety and invasiveness of acquisition, and the duration and conditions of preservation (i.e., address whether the tissue will be stored after the study is completed and, if so, why this is required);
d. The potential uses for the tissue, including any commercial uses, who the tissue might be sold to if this is known, and transfer to another institution;
e. The safeguards to protect the individual's privacy and confidentiality;
f. Access by other Investigators to banked tissue;
information attached to specific tissue, and its potential trace-ability;
h. Whether the subjects will be notified of the results, and if so, the provisions for counselling of subjects upon receipt of the results;
i. Whether tissue can be removed from the bank, if the subject later withdraws permission. In the case of a subject's withdrawal from a research study, TCPS Article 8.6 states that there may be a variety of options for dealing with the tissue or data, such as the "Actual destruction of genetic material or research data, or the removal of all identifiers." Any options must be discussed with the research subject and disclosed in the Consent Form.
39.6.2 Obtaining Consent for the Use of Primary and Secondary Data Collected from Personal Interviews, Surveys, Questionnaires, Observation Techniques, or Other Sources of Private Information
The consent form(s) must specify the following types of information.
a. The type of data to be collected;
b. The specific purpose for which the data will be used;
c. Limits on the use, disclosure and retention of the data;
d. Appropriate safeguards for security and confidentiality;
e. Any modes of observation (e.g., photographs or videos) or access to information (e.g., sound recordings) in the research that may allow identification of particular subjects;
f. Any anticipated secondary uses of identifiable data from the research;
g. Any anticipated linkage of data gathered in the research with other data about subjects, whether those data are contained in public or personal records; and
h. Provisions for confidentiality of data resulting from the research (including observational data).
39.7 CONSENT FORM STANDARD DISCLOSURES
See the CREB consent form template on the CREB website for descriptions of required components of the consent form. Other specific disclosures required by the CREB are outlined below.
Guidance Note #39 References:
#40: Conflict of Interest (Updated 22 December 2005)
As defined in UBC Policy #97: Conflict of Interest and Conflict of Commitment, Article 12.4., "in the research context, Conflict of Interest includes a situation where financial or other personal considerations may compromise, or have the appearance of compromising, an investigator's professional judgment in conducting or reporting research. Conflicts of interest may be potential, actual or apparent".
Even though Investigators may supply the information requested in the application to their departments or hospitals, the REB must consider whether this information has any bearing on the ethics of the research study. Furthermore, as stated in Procedure 2 of UBC Policy #97, assessors of annual conflict of interest disclosures by UBC members (with members being defined as faculty, clinical faculty and staff) will disclose the existence of the conflict of interest to the relevant REB where the conflict of interest relates to a particular research project. Note that "immediate family members" includes partners and children (whether living in the household or not). The REB does not require that the researcher declare holdings in managed mutual funds in the conflict of interest statements.
Subjects must be informed of significant individual financial conflicts of interest in the consent form.
40.2 PUBLICATION OF RESEARCH FINDINGS
The CREB will not permit any statements that appear to limit the researchers' rights to disclose their findings related to the research in publications or otherwise. The CREB upholds the following statement from the TCPS Section 7E: Analysis and Dissemination of the Results of Clinical Trials:
"In many clinical trials, the sponsors obtain contractual rights to the initial analysis and interpretation of the resultant data. Researchers and REBs must ensure, however, that final analysis and interpretation of such data remain with the researchers, whose duty it is to ensure the integrity of their research. ...Equally important, although sometimes more difficult to achieve, is the researchers' duty to disseminate the analysis and interpretation of their results to the research community. ...Researchers and REBs may exert pressure to alleviate this deficiency in the dissemination of research results by resisting publication bans in research protocols, on the basis of ethical obligations of truthfulness and the integrity of research."
40.3 RECRUITMENT FEES
The Canadian Medical Association Policy on Physicians and the Pharmaceutical Industry, Article 11 states: "It is acceptable for physicians to receive remuneration for enrolling patients or participating in approved research studies only if such activity exceeds their normal practice pattern. This remuneration should not constitute enticement. It may, however, replace income lost as a result of participating in a study. Parameters such as time expenditure and complexity of the study may also be relevant considerations. The amount of the remuneration should be approved by the relevant review board, agency or body mentioned previously (e.g. REB). Research subjects must be informed if their physician will receive a fee for enrolling them in a study".
40.4 PRECEPTOR AGREEMENTS
Disclosure to potential subjects is required where Preceptor agreements exist between a PI and a sponsor whereby the PI is consulted by the PIs at community sites for the same study; and where Preceptor agreements exist between a PI and a sponsor whereby the PI is consulted by the PIs at community sites for the same study.
Guidance Note #40 References: