1. 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

2. 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
Scholarly review
Privacy
Trainees
Badly written protocols/consent documents
Secondary use of data
Resources to navigate the REB
Questions

3. 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?)

4. Why? Social responsibility Integrity of research
Because we should
Social responsibility
Integrity of research
“The right thing to do”
Because we must
Legislated requirements
Guidance documents

5. 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
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

6. 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)

7. 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

8. TCPS2 Recognizes need for research Basic desire for new knowledge
Advance knowledge for the benefit of subjects
Benefits particular groups and society

9. Respect for Justice and Inclusiveness. Balancing Harms and Benefits.
Original 7 principles that form the basis for respect for human dignity
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.

10. Core Principle Respect for Persons (Human Dignity)
Fully informed consent
Voluntary participation
Participant anonymity
Data confidentiality
Special treatment of vulnerable populations
Third party consent
Treat subjects as autonomous beings
Respect the right to privacy
Protect subjects with limited autonomy

11. Core Principle Concern for Welfare – Do Good (Beneficence)
Study design
Subject screening and exclusion
Risk assessment
Benefits to subject
Benefits to society
Benefits should outweigh risks
Minimize Harm
Maximize Benefits
Risk/Benefit

12. 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

13. 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

14. 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 :
surveys,
questionnaires,
interviews,
human sampling (tissues),
human testing (physiological / psychological),
human observation (behavioral investigations)
clinical investigations

15. Scope of research needing review
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

16. 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

17. What doesn’t need ethics review?
Research using publicly available information
Archival or literature-based studies
Research about ‘public figures’ using published information or third-party interviews
Observation of public events
Quality Assurance (Q/A) studies
Program evaluations for direct local application
Performance reviews (educational purposes)

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. REB Review - Initial Full Review Delegated Review – Minimal Risk
Primary and secondary reviewer
All REB members read submission
Face-to-face discussion
Written recommendations
Major & minor revisions
Appeals process, if impasse
Primary and secondary reviewer assigned
Other REB members read submission, only if moved to full review
Written recommendations
Major & minor revisions
Appeals process, if impasse

25. REB Review - Ongoing
All ongoing research requires annual review (proportionate to risk)
Review of consent process
Safety monitoring committee
Review of study documents
Review of adverse events
Review of patient charts
Random audit

26. Practical Issues
Allow time to prepare REB submission
REB requires review of project by supervisor
Submission deadlines
IWK – 1st Tuesday of the month – REB meets on the 3rd Tuesday of the month (no meeting Jan & Aug)
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.

27. 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

28. 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

29. 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”.

30. 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

31. 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”.

32. 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”)

34. 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”

35. Essential Elements Research study Provision of new “Comprehensible
statement of purpose”
“Comprehensive description of reasonably foreseeable harms and benefits”
Free not to participate
Free to withdraw
Commercialization
Conflicts
Provision of new
information as available
Contacts
Ethics contact
Confidentiality
Subject responsibilities
Study termination
Costs/payments
Alternatives
Provision of results

36. Consent TCPS2 - Waiver of consent if all the following met:
No more than minimal risk,
Waiver unlikely to affect rights of subject,
Research cannot be practically carried out,
Subjects will be provided with additional info, when possible, AND
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.

37. 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.

38. Assent (Dissent) - elements
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

40. 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

41. 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

42. 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

44. Ethics Review in Clinical Trials
ICH-Good Clinical Practices
Adopted by Health Canada
Applies to Clinical Trials
Division 5
Health Canada legislation

45. 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.

46. 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. 

47. 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:
Clinical trials involving medical devices:

48. 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

49. 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.

50. 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

51. Contacts Ken Jenkins, Manager – 473-8426
IWK Health Centre - REB guidelines
Bev White –
Joanne Street –
Dalhousie Office of Research Ethics Administration
Catherine Conner, Director –
CDHA Research Ethics Board
Ken Jenkins, Manager –

52. Questions?