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UBC Clinical
Research Ethics Board Guidance Notes for New Applications for Clinical
Ethical Review |
Initial
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.
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GENERAL
INFORMATION 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.
External
Review 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: BC
Cancer Agency Research Ethics Board - reb@bccancer.bc.ca 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
appropriate REB. 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. GUIDANCE
NOTES
#1:
Principal Investigator 1.1
RESPONSIBILITIES OF A 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. 1.1.2.1
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) 2.1.1 Submission Criteria and Process for Expedited
Review of New Minimal Risk Applications 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. 2.1.2 Types of Minimal Risk Research Studies Qualifying
for Expedited Review 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 #2.1.2.1 and GN #2.1.2.2) and, as such, may undergo expedited review
by the CREB Chair (or designate). See GN #2.1.4 for
exceptions. 2.1.2.1 Primary Sources of Data Obtained For
Prospective Research (03 Jul 2008)
2.1.2.1.2 Consent Requirements Consent
must be obtained from subjects for the use of data derived from the preceding
sources. For further information, see GN 2.1.3. 2.1.2.2 Secondary Sources of Data Used for
Retrospective Research (24 September 2004)
2.1.2.2.1 Consent Requirements 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. 2.1.2.3 Case Reports of Individual Patients
That Will Be Submitted For Publication (Updated 22 December 2005) 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. 2.1.2.4 Stem Cell Research (Updated 22 December 2005) 2.1.2.4.1 Permanent Stable Cell Lines Ethical
review of research that uses permanent stable cell lines in laboratory
research (i.e. in vitro) is not required.(24 September 2004) 2.1.2.4.2 CIHR Requirements for Ethical
Review of Pluripotent Stem Cell Research (Updated 22 December 2005) 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). 2.1.2.4.3 CREB Criteria for Expedited
Review of Pluripotent Stem Cell Research (Updated 22 December 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:
Refer
to the CIHR
Guidelines for Human Pluripotent Stem Cell Research (updated June 2005) 2.1.3
Requirement for Consent Forms for Minimal Risk Applications 2.1.3.1 Circumstances Where Consent Is Required for Minimal Risk Studies Subject
consent IS required for collecting prospective subject data as described
above in GN 2.1.2.1 . 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. The
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. 2.1.3.2 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:
2.1.3.3 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) 2.1.3.4 Use of Data Obtained from Non-UBC Affiliated
Sites (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. 2.1.4 Minimal Risk Studies That Require Full Board
Review (03 Jul 2008) 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: BC
Cancer Agency Research Ethics Board - reb@bccancer.bc.ca 3.2 MECHANISM
FOR SUBMITTING THE FEE
3.3
REQUIREMENTS FOR FEE REFUND 3.3.1
Full Refund 3.3.2
Partial 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 Other 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. BC Cancer Agency
Research Ethics Board - reb@bccancer.bc.ca 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 UBC CREB POLICY #1:
Requirement for Research Protocol The UBC CREB requires
that a research protocol/research plan be submitted for all types of studies,
including pilot studies and retrospective chart reviews. The research
proposal submitted to granting agencies may be used to meet this requirement;
in this case, ensure that the appropriate section of the grant application is
referenced. For all other studies, including those that are submitted for
expedited review, investigators must submit a protocol that includes the
following components: 1.
a background literature review (with accompanying references) that
includes an explanation of the need/justification for the study, 2.
the study purpose, 3.
hypotheses, 4.
objectives, 5.
specification of endpoints/outcomes (if applicable), 6.
research design including statistical analysis plan (if applicable),
and, 7.
detailed research procedures. 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. Peer
review reports are strongly encouraged for new applications considered for
expedited review. Guidance Note #6 References:
[BACK TO TABLE OF CONTENTS]
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). [BACK TO TABLE OF CONTENTS] 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. 8.2 DECISIONS ARISING FROM THE REVIEW PROCESS (Updated 30 March 2007) 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 b.
Provisos 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. c.
Deferral 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. d.
Rejected
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) a.
Full
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. 8.3
APPEAL 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) 9.1 GRADUATE STUDENTS AND MEDICAL RESIDENTS If the
research is for a graduate degree or medical resident
include that information in question 1.3 of the application form. 9.2
CO-INVESTIGATORS 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. [BACK TO TABLE OF CONTENTS] 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. [BACK TO TABLE OF CONTENTS] 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:
[BACK TO TABLE OF CONTENTS] 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: 1.
Clinical trials for either drugs or devices - refer to GN
#12.1.2 and GN #12.1.3 , and the Therapeutics
Product Directorate 2.
Clinical trials for either biologics or radiopharmaceuticals - refer to GN #12.1.4 and the Biologics
and Genetic Therapies Directorate 3.
Clinical trials involving natural health products formulated for therapeutic
purposes - refer to GN #12.1.5 and the Natural
Health Products Directorate 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. 12.3
REGISTRATION OF CLINICAL TRIALS FOR PUBLICATION (22 December 2005) 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. For more
information, see the following articles: #13:
Research Proposal Summary The Research
Proposal Summary should include the following information: 1.
Purpose 2.
Hypothesis or Aim 3.
Justification for the
study 4.
Objectives 5.
Research Method 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. 15.2.1.1
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. 16.2 JUSTIFICATION FOR EXCLUSION 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) 17.1.2.1
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." 17.1.2.2
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 17.5.1
Letters 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 17.5.3.1
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. 17.5.3.2
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. 17.5.3.2.1
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 20.1 SUMMARY OF 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). 23.1.1.1
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. 23.1.1.2
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. 23.1.5.1
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 #39.7.1.2.1 [e53] ], medication implications for sexual partners as
well as the impact of a positive test on a subject's insurance policies. The
following websites provide some information on pre-test counseling for HIV
testing that can be applied to Hepatitis B and C as well: 23.1.5.2
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:
#24:
Benefits 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:
#27:
Monitoring 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 UBC Policy # 85: Scholarly Integrity Regulated
databanks may also have specific requirements for records retention, which
should be adhered to for studies using data from these sources. 29.4
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 30.1 PREVENTION OF UNAUTHORIZED ACCESS TO DATA 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.ulveteg@ubc.ca 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, “This online survey company is hosted by a websurvey company located in the USA and as such is subject to U.S. laws. In particular, the US Patriot Act which allows authorities access to the records of internet service providers. This survey or questionnaire does not ask for personal identifiers or any information that may be used to identify you. The websurvey company servers record incoming IP addresses of the computer that you use to access the survey but no connection is made between your data and your computer’s IP address. If you choose to participate in the survey, you understand that your responses to the survey questions will be stored and accessed in the USA. The security and privacy policy for the websurvey company can be found at the following link: ________”. 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) Please see
the CREB Consent Form Template on the CREB
website and GN #39 for more information on
procedures for obtaining consent 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 32.1.1.1 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. 32.1.1.1
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.] 32.1.1.2
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. The PI
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 UBC CREB POLICY # 17: OBTAINING ASSENT FROM SUBJECTS
WHO ARE LEGALLY INCOMPETENT (Approved 08 April
2003) 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) 35.5.2.1
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. 36.5.2.2
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). Provisions
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). Written
reconsent is required in situations when the information concerning risks has
the potential to affect the subject's decision to continue participation in
the study.
ICH GCP
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
subject's consent". 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 38.1 CONSENT PROCESS FOR NON-ENGLISH/ESL SPEAKERS 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) 39.1 CREB CONSENT FORM TEMPLATE 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." 39.2.1 Obtaining Consent For Studies Using
Questionnaires Non-identifiable
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). a.
That
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: 39.6.1.1.
Mandatory Tissue Banking 39.6.1.2
Donation of Tissue For Unspecified Uses 39.6.1.3
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; g.
Identifying
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) 40.1 POTENTIAL 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:
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