Ethics Training

1. Ethics Training Dr Nik Zeps

2. What is Ethics? • Moral philosophy • Right and wrong • Good and bad • Justice and virtue

3. Codes of ethics • Applied ethics • Not always dichotomous • Bioethics • Coined in 1927 by Fritz Jahr • Field emerged in last 90 years • Prompted by unethical behaviour

4. “getting” ethics

5. The Ethics Framework • Australian Context • Guidelines • Legislation • Policies

6. Research merit and integrity • Justice • Beneficence • Respect for human beings 6

7. Code of Responsible Conduct • Is mandatory to implement by Australian Research Institutes • But who does? • Training? • Written policies on data collection, retention, distribution? • Key to public trust is transparent and accountable researcher behaviour

8. HRECs or other? • Who is required to do the review? • 5.1 Institutional responsibilities • 5.1.3 Institutions may establish their own processes for ethical review of research, or use those of another institution. • 5.1.7 (low risk-5.1.18-5.1.21) and 5.1.8 (negligible risk 5.1.22-5.1.23)

9. NS: Ethical Considerations • Guided by the National Statement on ethical conduct in human research 2007 • Not simply a matter of regulatory compliance • 1.1 Research Merit and Integrity • Is the study worth doing? • Are those doing the work competent and trustworthy? • 2 Risk and benefit • Consent • 3 Specific types of research • 4 Specific populations • 5 Governance and ethical review

10. Important Distinctions 10 …between substantive ethics and regulatory ethics …between ethics and governance …between ethics/governance and bureaucracy J Kenner 2010

11. Substantive Ethics vs Regulatory Ethics • “Substantive (research) ethics” relates to the evaluation of proposed research with a view toward ensuring proper respect for and protection of participants in that research as well as the promotion and facilitation of good research design and practice. • “Regulatory ethics” involves the quasi-regulatory, administrative systems used to review and approve proposed research. • J Kenner 2010

12. Components of Research Governance • Site-related assessments prior to project start-up • Fit with organisational priorities • Clarification of roles and responsibilities • Identification of potential/actual conflicts of interest • Supervisory relationships • Credentialing • Assessment of resources • Completion of grants processes • Budgetary matters • Contractual relationships/documentation (including IP and publication) • Establishment of proper indemnity/insurance coverage • Compliance with relevant laws/regulations/codes/guidelines/policies • Ethics approval, including scientific/technical assessments • Other risk management considerations J Kenner 2010

13. Components of Research Governance • Responsibilities during research and after project completion • Monitoring by HREC of conditions of approval • Safety of participants • Data management and storage/confidentiality of research data • Financial management • Training/supervision/mentoring within project team • Exposure and management of research misconduct • Compliance with progress reporting obligations • Auditing (self, internal and external) • Managing complaints/concerns of (a) research team and (b) participants • Ensuring proper project closure processes • Final reporting • Ensuring promised feedback to participants is provided • Monitoring security of data/tissue sample storage (including destruction, if intended) • Consideration of secondary use of data/tissue samples J Kenner 2010

14. The Governance – Ethics Hierarchy • Old model = Research projects are reviewed by a local HREC. (Many) governance matters devolved to site ethics administration. • Current model = Ethical review and research governance sit side by side as related and complementary processes. Promotes introduction of streamlined review programs. • Future model = Recognition that ethical review is but one component (amongst many) of research governance within an organisation. Note: The last model more readily liberates an organisation to devolve ethical review to off-site HRECs if it wishes to – for single-site research as well as multi-centre research. J Kenner 2010

15. Beyond Ethics and Governance Bureaucracy … • Refers to administrative aspects of review and governance of research that do not appear to have a rational purpose in promoting or protecting the interests of participants, researchers or research sites • Usually emanates from misinterpretation or overzealous application of regulatory requirements or requirements developed by lawyers or wanna-be-lawyers that have not previously been considered necessary J Kenner 2010

16. Beyond Ethics and Governance (2) • UFO = Unnecessary Formalistic Obstruction • Consequence of blind adherence to (apparent) regulatory requirements • The problem of “Ethics Creep” • Forces re-consideration of what we who are responsible for review, approval and monitoring of research are doing J Kenner 2010

17. E vs G vs B – Which is Which? • Proper insurance coverage • Proposed consent processes for eligible participants lacking decisionmaking capacity • Review of collaborative research agreements • Review of budget • Statistical rigour • Amendment to a protocol • Correspondence announcing an upcoming amendment to a protocol • Reporting of expected adverse events from Sweden • Sign off from the hospital IT department or outpatient clinic • Sign off from Associate Investigators • Typographical errors in the PICF form • Typographical errors on the application form • Repetition of participant information sheet information on the consent form • Sponsor requirement for inclusion of US law references in an Australian PICF • Disclosure of potential conflict of interest of the Principal Investigator • Disclosure of potential conflict of interest of a study coordinator • Sponsor requirement for responsive correspondence from the HREC regarding submission of a file note • Review of request for patient input on layout of reception area J Kenner 2010

18. HoMER and 5.3.1 • Wherever more than one institution has a responsibility to ensure that a human research project is subject to ethical review (see paragraph 5.1.1, page 77), each institution has the further responsibility to adopt a review process that eliminates any unnecessary duplication of ethical review. • HoMER provides a framework to deliver on 5.3.1

19. Benefits and risks: risks and review NS identifies three risk levels and relates these to proportionate levels of ethical review More than low risk = risk is more than discomfort: HREC review required Low risk = risk is no more than discomfort: Low risk review mechanism permitted Negligible risk = risk is no more than inconvenience: ONLY WHERE research uses EXISTING collections of non-identifiable data about human beings, institutions MAY exempt research from review

20. Low risk research 5.1.7 • For research that carries only low risk (see paragraph 2.1.6, page 18) and does not fall under any of the chapters listed in paragraph 5.1.6, institutions may choose to establish other levels of ethical review. • These levels are described in paragraphs 5.1.18 to 5.1.21.

21. Low risk research • 5.1.20 The levels of ethical review referred to in paragraph 5.1.18 may include, but need not be limited to: • (a) review or assessment at departmental level by the head of • department; • (b) review or assessment by a departmental committee of peers • (with or without external or independent members); • (c) delegated review with reporting to an HREC; or • (d) review by a subcommittee of an HREC.

22. Quality Improvement vs Research • Means to avoid review • Not defined by whether intend to publish • Ethics review should be determined by consideration of ethical issues • Some don’t believe researchers capable of this • But doesn’t have to be an HREC • Currently a project for AHEC

23. Elements of a Good Ethics Application • Communication • Application form • Supporting documents • Interview • National Ethics Application Form (NEAF) is a means to communicate that researchers have recognised and addressed the ethical issues

24. NEAF - aims 24 Designed to collect • in one application all information about a human research proposal that an HREC reviewing that proposal would need, so as to be satisfied that • the proposal met the relevant requirements of the National Statement and was ethically acceptable . Hence, use of helps: • Information buttons – explain what terms meant • Guidance buttons – help in answering questions • National Statement links – to relevant paragraphs of NS • Help phone line

25. NEAF • Demonstrate that ethical issues have been considered • NEAF sections • 1 Title and Summary • 2 Researchers and investigators • 3 Resources • 4 Prior Reviews • 5 Project • 6 Participants • 7 Participants specific • 8 Confidentiality/ Privacy • 9 Project Specific

26. NEAF Demo

27. Why do we ask for consent? • Respect (NS 1.10) • Expression of Autonomy • empowerment • Altruism • Compliance with guidelines/legal requirements

28. Demonstrating Trust • Consent is the material demonstration of a process that indicates a patient ‘trusts’ the person/system they give it to. • Alternatives to consent are community trust in a system that demonstrates responsibility and accountability

29. Consent (Chapter 2.2) • Respect for a person = consent • Voluntary • Informed • Considerations • Communication • Mutual understanding • No coercion or pressure • Payment for participation

30. Competence • Functional approach not status based • Competence to make particular decision at particular time

31. Incompetence Competence Simple Complex

32. Information • Providing information is not merely satisfying a formal requirement (2.2.4) • Material information - participant centred concept • Information that a reasonable person would think was significant for making the decision to participate

33. Skills for obtaining consent • NS 3.1.13   Predicting what topics are likely to lead to distress will not always be easy. Researchers should have sufficient training to help them in making such predictions.

34. Flexibility • NS 3.1.16   The method of providing consent in qualitative research depends on various factors, including the type of research, its level of sensitivity, its cultural context, and the potential vulnerability of the participants. In some contexts, the protection of vulnerable participants may favour a formal, written process of consent; in other contexts, an oral process.

35. Implied consent • NS 3.1.17   In some circumstances, consent may be implied by participation, for example the return of a survey, or the answering of a verbal question

36. Renegotiating consent • 2.2.8 In some research, consent may need to be renegotiated or confirmed from time to time, especially where projects are complex or long-running, or participants are vulnerable. Research participants should be told if there are changes to the terms to which they originally agreed, and given the opportunity to continue their participation or withdraw (see paragraphs 5.2.16 and 5.2.17, page 84).

37. Research participants – impaired consent 37 Coercion NS 2.2.9 } limited disclosure Deception NS 2.3.1-2.3.4} NEAF 5.1.2 Dependent relationships = example of coercion NEAF always asks about this – 6.4.1 – 6.4.5 NEAF 6.1.1 assumes knowledge of examples in NS 4.3 See also other NS references, e.g. NS 3.1.3-3, 3.3.13-18 Leads to NEAF 7.4 Inducement NS 2.2.10/11* NEAF 6.6.1.. *NHMRC Using the NS: payment

38. Waiver of Consent • Section 2.3.6 of the NS • A) low risk • B) benefits outweigh harms • C) Impracticable to get consent • D) No reason why a person would say no • E) Privacy protected • F) Adequate plan to protect confidentiality • G) A plan to feedback results (or not) • H) Commercial outcomes will not cause disadvantage • I) Waiver is not unlawful

40. Privacy and Confidentiality • Privacy Laws • Commonwealth • State • Private sector • Confidentiality • Requirement of employment contract • Guarantee to patients (participants)

41. Potential Harms • Invasion of privacy • A sense of violation • Concerns regarding • inappropriate use • who has access • What use the information is put to

42. A Good PICF – The Basic Elements • Invitation • Nature and purpose of research • Procedures/requirements of participation • Risks and potential benefits • Alternatives to participation • Voluntary participation/right to withdraw • Privacy and confidentiality • Sponsorship/financial support • Reimbursement (if any) • End of project • Reasons for termination • Consequences for participant • Availability of results • Who to contact re concerns or complaints • Approval by HREC • Consent Form

43. Breakout into table discussion Issues related to recruitment of specific groups • Consent processes • how much to rely upon PICF or are there other considerations more important? • Feedback/discussion

44. Alternative processes • Standard information and process for recruitment in departments that do research • Only provide information about • non-standard therapies and procedures • Additional burdens and risks • No PICF should be longer than 2 pages • Current system ignores usual practice and leads to the conclusion that the only item of importance is the PICF

45. Break for Lunch

46. Research Involving Human biospecimens • Translational Research?‘ • Bench to bedside and back again’ • Requires a multidisciplinary team approach • Laboratory • Clinical • Health Services • Primary care

47. Clinical trials Advances in Technology Lab tests Clinical practice Phase 1:Right dose? Phase 2:Can it work? Phase 3:What is best? Developing new treatments Preclinical testing

48. Medical notes • Diagnostic Tests • Pathology • Imaging • Genetics • Medical History Clinical Phenotyping Treatment • Standard • Trial Follow Up Clinical Practice Patients Clinical Registries

49. Biospecimens • Clinical Phenotype Genomics-Proteomics • Genotyping Follow Up • Prognosis • Prediction Clinical Research Patients Research Databases

50. Types of ‘biobank’ • Population based • Dedicated collections eg Busselton • Pathology services • Surgical resections • Biopsies • ‘Waste’ blood • Mortuary • Outpatient (biopsy/blood) • Direct to researcher