Responsible Conduct of Research

1. Responsible Conduct of Research Professor A Dhai Head – Bioethics Discipline Wits Medical School Wits – GEMP Medical School Day

2. Introduction • 2 fundamental objectives of ethics: ● How we ought to act in a given situation ●Provide us with strong reasons for doing so involves a critical reflection of morality with its intent to safeguard human dignity and to promote justice, equality, truth, and trust.

3. Research Ethics About means of ensuring vulnerable people are protected from exploitation and other forms of harms Evolving language : passive subject → active participant

4. Vulnerable: DOH / UNAIDS Guidelines • limited economic development • inadequate protection of human rights & discrimination on basis of health status • inadequate community / cultural experience with understanding of scientific research • limited availability of health care & treatment options • limited ability of individuals in community to provide informed consent

5. Ethical Concepts Principle-based Ethics • Autonomy • Beneficence • Non-maleficence • Justice Prima facie – not absolute; overridden by weightier concerns - lack hierarchical order rendering ranking arbitrary

6. Ethics & Law • Distinct entities • Ethics constrained by law • Law: minimal standard • Quasi legal status of guidance documents

7. Analysis Process • Determine whether issue at hand is ethical one • Check facts of the case • Check for constraints on actions • Check which ethical values are involved • Consult authoritative sources • Consider alternative solutions in light of values and principles they uphold & their likely consequences • Discuss proposed solutions with those whom it will effect • Make decision – act on it with sensitivity to others affected • Evaluate decision – be prepared to act differently in future

8. What are the boundaries between practice and research especially when the distinction is blurred partly because both often occur together?

9. PRACTICE ● Interventions designed solely to enhance wellbeing of patient and that have reasonable expectation of success ● Purpose – provide diagnosis, preventative treatments or therapy

10. Research ● Activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to to generalizable knowlege

11. DEFINITIONS - Health Research (NHA) • a) biological, clinical, psychological, social processes in human being; • b) improved methods for provision of health services; • c) causes of disease, • d) effects of environment on human body; • e) development of new application of pharmaceuticals, medicines and related substances • f) development of new applications of health technology

12. ETHICS IN RESEARCH ♦Understanding the need for ethicsin research How can the rights of individual participants be reconciled with the demands of the scientific enterprise?

13. Natzi War Experiments – some examples • High Altitude (low pressure) experiment • Put into low pressure tanks to see how long they could survive with little oxygen. If did not die immediately, put under water – autopsies followed • Freezing Experiments • forced to remain outdoors without clothing in freezing weather for 9-14 hrs, or in bath of freezing water for 3 hours. Then re-warmed if did not die • Malaria experiments • infected then given “antimalarial drugs”. Died from drugs • Sulphanilamide • Experiments Wounds inflicted then infected with bacterial or gangrene producing culture, wood shavings, glass shards. Followed by treatment and placebo group expertiments • Sterilization • chemical and Xray sterilization experiments

14. Transgressions Post Nuremberg • Tuskegee Syphilis Study • Willowbrook Hepatitis Study • Bezwoda • Virodene

15. ETHICS IN RESEARCH • Knowledge of: Guidance documents • Regulations • Past & current debate

16. Declarations and Codes • 1947 Nuremberg Code • 1964 Declaration of Helsinki • 1979 Belmont Report • 1982 CIOMS • 1991 Common Rule • 2000 DOH SA Clinical Trials Guidelines • 2004 DOH Principles Structures & Processes

17. Research Ethics Components • Procedural • Substantive

18. Role of REC Review • Primary role – protection of rights & welfare of research participants : Provide ethical advice to researchers to assist decision-making on adequacy of proposed research projects regarding participant protection • RECs also serve to protect investigators from unjust criticism • REC principles: competence, independence, pluralistic, transparent

19. Some Benchmarks • Collaborative Partnerships • Value • Validity • + Benefit / Risk ratio • Respect for persons • Just & Fair processes • Avoiding Conflicts of Interest

20. NHA – CONSENT & RESEARCH • 16(a) access to health records – authorization of user, head of health establishment & REC • 76(1)(b) adult - written consent • 76(2) minor – therapeutic research • 76(3) minor – non therapeutic research

21. Privacy & Confidentiality • Privacy – access to personal records (3rd part access) • Confidentiality – use of personal information once it has been disclosed • Privacy & confidentiality to be protected • Informed consent – inform participants of: precautions to protect confidentiality limits to ensuring strict confidentiality foreseeable adverse social consequences of breaches of confidentiality reporting of communicable diseases & child abuse & neglect

22. Plans for dissemination of results • Communities • Policy makers & health authorities • Publication • Conditions of publication to be spelt out clearly in protocol & REC to be satisfied that no interference with right to publish

23. Conflict of Interest • “set of conditions in which professional judgement concerning a primary interest tends to be unduly influenced by a secondary interest.” Thompson • “set of circumstances in which a clinician’s or investigator’s own interests conflict with those with whom he/she has a fiduciary relationship” Sugarman • “when a secondary interest compromises or appears to compromise or has a potential to compromise an individual’s professional judgement towards the primary interest (people, institution, research).” AAU

24. Research – Types of Conflicts of Interest • Financial • Non-financial conflicts

25. Scientific Misconduct “Research misconduct is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.” Fabrication: making up data or results and recording or reporting them. Falsification: manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record. Plagiarism: appropriation of another person's ideas, processes, results, or words without giving appropriate credit. Research misconduct does not include honest error or honest difference of opinion.” (http://www.ostp.gov/html/001207_3.htm)

26. Scientific Misconduct Deviation from or failure to adhere to the proposed protocol without proper permission Misrepresentation Falsification of credentials Deception in the research proposal Deception in the carrying out of research Piracy of materials Failure of informed consent Breaches of confidentiality Anyone of all other deviations from accepted ethical standards.

27. Scientific Misconduct Requirements : Significant departure from accepted practices of relevant research community; Misconduct committed intentionally, knowingly, recklessly; Allegation proven by preponderance of evidence Serious disciplinary offense!

28. Research Misconduct • Tuskegee • Bezwoda

29. HOMEWORK http//:www.ethics.medschool.co.za dhaia@medicine.wits.ac.za

30. USEFUL WEBSITES ٠Ethics in Health Research: Principles, Structures and Processes www.doh.gov.za ٠MRC Guidelines on Ethics for Medical Research: www.mrc.ac.za ٠Nuffield Council on Bioethics. The ethics of research related to healthcare in developing countries. www.nuffieldbioethics.org ٠Council for International Organizations of Medical Sciences (CIOMS) www.cioms.ch/guidelines_nov_2002_blurb.htm ٠Emanuel et al. What Makes Clinical Research in Developing Countries Ethical? The benchmarks of Ethical Research. www.journals.uchicago.edu/JID/journal/issues/v189n5/31380/31380.text.html