Bev White, Manager, Research Ethics Research Services , IWK Health Centre

1. IWK Research Ethics - Workshop Series Session #1Why 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? Because we should • Social responsibility • Integrity of research • “The right thing to do” Because we must • Legislated requirements • Guidance documents

5. Research EthicsGuidance 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

6. TCPS2 • The TCPS2 describes principles, standards and procedures for governing research involving humans. • The TCPS2 applies toallresearch 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. 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 PrincipleRespect for Persons (Human Dignity) • Treat subjects as autonomous beings • Respect the right to privacy • Protect subjects with limited autonomy • Fully informed consent • Voluntary participation • Participant anonymity • Data confidentiality • Special treatment of vulnerable populations • Third party consent

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

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 assigned Other REB members read submission, only if moved to full review Written recommendations Major & minor revisions Appeals process, if impasse • Primary and secondary reviewer • All REB members read submission • Face-to-face discussion • 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 • “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 • EASForm 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. • http://www.hc-sc.gc.ca/dhp-mps/compli-conform/index_e.html

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: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/clini/index_e.html • Clinical trials involving medical devices: • http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/guide-ld/test_md3_im3_main_principal-eng.php

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