IWK Research Ethics - Workshop Series
Session #1
Why do we need
Research Ethics Approval?
October 21, 2013
Bev White, Manager, Research Ethics
Research Services, IWK Health Centre
Objectives
• Research Ethics Review – why do we have it?
• Mandate/Role of the REB
• Guidance documents
– TCPS2, Division 5, ICH-GCP, PHIA, etc…
• Specific Issues of Interest
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Scholarly review
Privacy
Trainees
Badly written protocols/consent documents
Secondary use of data
• Resources to navigate the REB
• Questions
Research Ethics Review
 Nuremberg Code (1947)
 Universal Declaration of Human rights (1948)
 Tuskegee, Willowbrook (1932/72, 1960/70)
 Declaration of Helsinki (1964) – modified x 5
 MRC/Canada Council Guidelines (1978)
 Health Canada – ICH-GCP (1997)
 TriCouncil Policy Statement – 2
(CIHR, NSERC, SSHRC) (1998, 2010, 2013?)
Why?
Because we should
– Social responsibility
– Integrity of research
– “The right thing to do”
Because we must
– Legislated requirements
– Guidance documents
Research Ethics
Guidance Documents and Regulations
• TCPS-2
Applies to all human research
• Division 5
Health Canada legislation
• ICH-Good Clinical Practices
Adopted by Health Canada - Applies to Clinical Trials
• Best Practices for Health Research Involving Children and
Adolescents http://www.pediagen.org/ressources/BestPratice.pdf
•Personal Health Information Act - PHIA
US Regulations - Office of Human Research Protections - OHRP
CFR 45, Part 46 - Department of Health and Human
Services, Protection of Human subjects
CFR 21, FDA – Protections of Human Subjects, IRB(REB),
Drugs & Devices
TCPS2
The TCPS2 describes principles, standards and procedures
for governing research involving humans.
The TCPS2 applies to all research involving human or
human tissues affiliated with, and undertaken by members
of, research institutions administering funds awarded by any
of the three federal granting agencies (CIHR, NSERC and
SSHRC).
It includes new chapters:
•Multi-Jurisdictional Studies, (Ch. 8),
•First Nations, Inuit & Métis Research (Ch. 9)
•Qualitative Research (Ch. 10)
TCPS2
 Addresses the interdependent duties shared by
researchers, institutions and REBs
 Articulates and updates ethical norms - encourages
continued reflection on complex ethical issues.
Seeks to avoid imposing one disciplinary perspective
 Harmonize the ethics review process
TCPS2
• Recognizes need for research
– Basic desire for new knowledge
– Advance knowledge for the benefit of subjects
– Benefits particular groups and society
Original 7 principles that form the basis for respect
for human dignity
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Respect for Justice and Inclusiveness.
Balancing Harms and Benefits.
Minimizing Harm
Maximizing Benefit
Requirement for Free and Informed
Consent.
• Respect for Vulnerable Persons.
• Respect for Privacy and Confidentiality.
Core Principle
Respect for Persons
(Human Dignity)
• Treat subjects as
autonomous beings
 Fully informed consent
 Voluntary participation
• Respect the right to
privacy
 Participant anonymity
• Protect subjects with
limited autonomy
 Special treatment of
vulnerable populations
 Third party consent
 Data confidentiality
Core Principle
Concern for Welfare – Do Good
(Beneficence)
 Minimize Harm
• Study design
• Subject screening and exclusion
• Risk assessment
 Maximize Benefits
• Benefits to subject
• Benefits to society
 Risk/Benefit
• Benefits should outweigh risks
Core Principle
Justice – Be Fair
• Distribute benefits and risks
equitably
• Avoid exploitation of
vulnerable populations
 Link risks to benefits
 Allow all groups
access to benefits of
research
 Select subjects
equitably
Mandate
• REB structure and function dictated by the
Tri-Council Policy Statement on Ethical Conduct for
Research Involving Humans
– Explicit instructions regarding all aspects
• All organizations and institutions receiving funding from the
Tri-Agencies (CIHR, NSERC, SSHRC) must comply with TCPS2
TCPS2 Section1 Article A1.1
•
All research that involves living human subjects requires review and approval
by an REB “…before research is started”
•
Research is defined as “systematic investigation to establish facts, principles or
generalizable knowledge”
 includes both quantitative and qualitative methodologies :
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surveys,
questionnaires,
interviews,
human sampling (tissues),
human testing (physiological / psychological),
human observation (behavioral investigations)
clinical investigations
Scope of research needing review
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Whether the research is funded or not
Whether the subjects are from inside or outside the university
Whether subjects are paid or not
Whether the research is inside or outside of Canada
Whether the research is conducted inside or outside the
university
• Whether the research is conducted by staff or students
• Whether the research is conducted in person or remotely
Scope of research needing review
 Whether the research is to be published, or not
 Whether the research is collected from subjects or from records
not in the public domain (e.g. database research)
 Whether the research is observational, experimental,
correlational or descriptive
 Whether or not a similar project has been approved elsewhere
 Whether the research is a pilot study or a fully developed study
 Whether it is basic or applied research
 Whether the research is for teaching or training or for the
acquisition of new knowledge
What doesn’t need ethics review?
Research using publicly available information
• Archival or literature-based studies
• Research about ‘public figures’ using published information or thirdparty interviews
• Observation of public events
Quality Assurance (Q/A) studies
• Program evaluations for direct local application
• Performance reviews (educational purposes)
Secondary Use of Data
• TCPS2: “Use in research of data contained in records collected for a
purpose other than the research itself” – e.g. Health Records
• “If identifying information is involved, [full] REB approval shall be
sought”
– Justification for use of identifying information
– Protection of privacy and minimization of harms
– Individuals have not objected to secondary use
• If no identifying information, still need REB review and approval
– Generally will be expedited
Role of the REB
TCPS2 – Chapter 6 - Governance of the REB
• Independent Authority
• REB mandate is to review and then approve, reject, propose
modifications or halt proposed or ongoing research involving
humans at the institution.
• Institution may not override decisions
Research Ethics Board
Membership (minimum 5)
• 2 members with broad expertise in scientific methods
• 1 member knowledgeable in ethics
• 1 member knowledgeable in law
• 1 member from community
Institutional Accountability
• Each local REB must review research in multi-center research
• There must be local (international site) and institutional (home
institution of investigator) review for international research
• Grant awards DO NOT EQUAL REB approval (you may not begin
recruitment, data collection until you have written REB approval
Not the Role of the REB
• NOT to obstruct the conduct of research
• NOT to rewrite badly constructed consents
• NOT to revise badly written protocols
• NOT to require idiosyncratic changes to protocols or
consents
• NOT to nit-pick protocols
Common Ethical issues in research…
• Disclosure of illegal activities
• Disclosure of child / adult abuse
• Disclosure of previously unknown diagnoses
(mental or physical)
• Significant physical discomfort / harm
• Significant emotional / psychological distress
REB Review - Initial
Full Review
Delegated Review – Minimal Risk
• Primary and secondary reviewer • Primary and secondary reviewer
assigned
• All REB members read submission
• Other REB members read submission,
only if moved to full review
• Face-to-face discussion
• Written recommendations
– Major & minor revisions
• Written recommendations
– Major & minor revisions
• Appeals process, if impasse
• Appeals process, if impasse
REB Review - Ongoing
• All ongoing research requires annual review (proportionate
to risk)
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Review of consent process
Safety monitoring committee
Review of study documents
Review of adverse events
Review of patient charts
Random audit
Practical Issues
• Allow time to prepare REB submission
• REB requires review of project by supervisor
• Submission deadlines
o IWK – 1st Tuesday of the month – REB meets on
the 3rd Tuesday of the month (no meeting Jan &
Aug)
o CDHA – Every Friday – 6 days prior to the
meeting, REB meets every Monday
• Delegated review (minimal risk) projects can be submitted
at any time at the IWK.
Practical Issues
 Follow the instructions on the website
 Add a cover letter if there are special circumstances that the REB needs to
be aware of
 Provide point by point responses to all items
 Revisions - Highlight changes in relevant documents; Consents, etc.
 Revisions - Remember to change version date
 Consider your submission package to be the first step in your conversation
with the REB
Practical issues - Continuing Review
• Annual review will require summary of progress to date, unanticipated
problems, recruitment.
• If a change is needed for any reason during the conduct of the project
– an amendment to REB must be submitted. Include revised consent
documents (or related materials) with changes highlighted.
• The REB and Research Services are here to help you
Protecting Research Participants
• Ensure all research is conducted ethically
• Based upon ethical principles
– Respect for individuals
– Minimize risk/maximize benefit
– Justice and Inclusiveness (Be fair)
• “Aim is to prevent unintentional use of a human being solely as a
means toward even a legitimate end”.
Protecting Investigators &
the Institution
• Be aware of and vigilant for issues which may compromise
participant safety
• Assist investigators in developing research which meets
relevant regulations
• Educate investigators in issues of research ethics
Scholarly Review
• Has been a sore point
• “Bad science cannot be good ethics”
• TCPS2: “The REB shall satisfy itself that the design of a research
project that poses more than minimal risk is capable of addressing the
questions asked in the research”
• “Avoid duplicating previous professional peer-review assessment
unless there is a good and defined reason for doing so”.
What is research ethics about?
• Applying the principles of ethics to a particular
research context
• Three main principles:
– Respect for Persons (Free & Informed)
– Concern for Welfare (Beneficence …
“Do good”)
– Justice (Equality & Inclusiveness ….“Be fair”)
Informed Consent
• A process, not a piece of paper, BUT…
• TCPS2: “Researchers shall provide … full and frank
disclosure of all information relevant to free and informed
consent”
• “Must ensure that prospective subjects are given adequate
opportunities to discuss and contemplate their
participation”
Essential Elements
• Research study
• “Comprehensible
statement of purpose”
• “Comprehensive
description of reasonably
foreseeable harms and
benefits”
• Free not to participate
• Free to withdraw
• Commercialization
• Conflicts
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Provision of new
information as available
Contacts
Ethics contact
Confidentiality
Subject responsibilities
Study termination
Costs/payments
Alternatives
Provision of results
Consent
TCPS2 - Waiver of consent if all the following met:
1. No more than minimal risk,
2. Waiver unlikely to affect rights of subject,
3. Research cannot be practically carried out,
4. Subjects will be provided with additional info, when
possible, AND
5. Consent does not involve a therapeutic intervention.
PHIA – Consent of the subject individuals is required
unless a REB has determined that the consent is not
required, or that it is impracticable to obtain consent.
Assent (Dissent) - children
 The discussion process with a Child taking part in research
based on “Authorization” from their parent (or guardian)
 Involving participants in decision-making when they do not
have the ability to provide informed consent.
◦ Respect children as persons
◦ Honour developing autonomy
◦ Respect parent’s roles in guiding moral development
◦ Flexibility is key
 Seeking assent may not always be appropriate. Dissent must
be respected – if you ask, you must be prepared to respect a
“NO” answer.
Assent (Dissent) - elements
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Provide appropriate information
Include children in decision-making
Integrate family decision-making
Process over time
Determine capacity to assent
Document assent process
Process may be verbal…signature not required
Pay attention to soliciting/respecting dissent
Supporting Documentation
• To do its job, REB needs all materials pertaining to the
research
– Complete protocol
– Consent documents
– Posters/flyers/advertisements
– Budget
– CV’s
• EAS Form  directed towards lay members of committee
Privacy Legislation
—
Legislation governs the collection, handling, storage of personal
information, including research records.
◦ PIPEDA - Personal Information Protection and Electronics Documents
Act
◦ Nova Scotia Hospitals Act
◦ PIIDPA - Nova Scotia Personal Information International Disclosure
Protection Act
◦ PHIA - Nova Scotia Personal Health Information Act
 Guidance document
◦ CIHR Best Practices for Protecting Privacy in Health Research (2005)
◦ PHIA Toolkit
Data Collection and Management
• Affects
– What data you collect (minimum)
– How you handle it (storage, sending out)
– How long you keep it
• Impact on recruiting
– “Initial contact with individuals about a research project should be
made by someone that individuals would expect to have relevant
information about them”
• Future contact ask for permission
Ethics Review in Clinical Trials
• ICH-Good Clinical Practices
– Adopted by Health Canada
– Applies to Clinical Trials
• Division 5
– Health Canada legislation
Clinical Trial Application
• In September 2001 Health Canada Food and Drug
Regulations (Part C, Division 5) were amended to require
sponsor submission of a clinical trial application (CTA) for
drug trials.
• http://www.hc-sc.gc.ca/dhp-mps/compliconform/index_e.html
Clinical Trial Application
• Following receipt of a CTA by a study sponsor and Health
Canada's internal review:
– 'No objection letter' or
– 'Not satisfactory notice' is issued by Health Canada.
• IWK REB withholds its REB approval pending receipt of a copy of the
study's 'No objection letter'.
• Investigators are encouraged to initiate the CTA process early.
• Protocol amendments need to be submitted to Health Canada for
approval.
Clinical Trial Application
• A similar Health Canada review and approval process exists for Natural
Health Products and Medical Devices:
• Clinical trials involving natural health products. Under the Natural
Health Products Regulations
– Web site: http://www.hc-sc.gc.ca/dhpmps/prodnatur/applications/clini/index_e.html
• Clinical trials involving medical devices:
– http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/guideld/test_md3_im3_main_principal-eng.php
Research Ethics Cooperation Agreement – IWK,
CDHA, Dal
• Dal Health Sciences REB accepts IWK or CDHA
review
• IWK and CDHA do not accept Dal review, if
patient related
• IWK and CDHA can not accept each other’s
review, if patient related
Memorandum of Understanding IWK, CDHA
• Researchers who have dual appointments – the REB of
record will forward copy of approval to the other institution
• Expedited review – Advertisements and Use of Resources
• Industry funded research - conducted at both institutions
requires full Board review by both institutions.
REB Audit – Typical Results
• Research records taken out of Health Centre
• Study documents misplaced
– Health Canada requires originals
• Protocol changes without REB approval
• Personnel changes without amendment
• Personal health information on laptops
Contacts
•
IWK Health Centre - REB guidelines
http://www.iwk.nshealth.ca/research/application-materials-forms
Bev White – 470-8520
bev.white@iwk.nshealth.ca
Joanne Street – 470-7879
joanne.street@iwk.nshealth.ca
•
Dalhousie Office of Research Ethics Administration
http://researchservices.dal.ca/research_1482.html
Catherine Conner, Director – 494-1462
•
CDHA Research Ethics Board
http://www.cdha.nshealth.ca/discovery-innovation/ethics
Ken Jenkins, Manager – 473-8426
Questions?