Ethical Review and Ethical Issues in. Science Research. Doug Wassenaar PhD. Initiative

Transcription

1 Ethical Review and Ethical Issues in Health & Social Science Research Doug Wassenaar PhD South African Research Ethics Training Initiative SARETI Fogarty International Center, National Institutes of Health Grant Number 2 R25 TW

2 Aims of the session To provide a perspective on the importance of research ethics in NTD and health research To provide a model for conceptualising ethical issues in health research To provide an opportunity to apply this model to NTD research Bamako

3 What is the role of ethics in research with human participants? p The objective of research is to develop generalisable knowledge e.g. to improve health and/or increase the understanding of aspects of life, the world etc. The aims of research are a recognized good, but research has the potential to inflict harms and to treat participants as just means to an end The aim of ethics is to ensure that participants are treated with dignity and respect while they contribute to the social good Ethics may help us find the least harmful route Bamako

4 Role of Ethics in Research Ethics aims to protect participants from harm and to promote their welfare: acts to restrain science However, ethics also promotes good science as participants who feel respected may: Actively engage with research requests Answer truthfully, comply with protocol Provide critical & honest feedback Return for follow up Therefore increasing the quality of the data Bamako

5 Number of Overseas Human Clinical Trials for New Drugs Developed Countries Less Developed Countries '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 Sources: FDA Biomonitoring Research database; Parexel s Pharmaceutical R&D Statistical 5 Sourcebook 1999; Aculaunch; Washington Post Research

6 Overseas Spending by U.S. Pharmaceutical Companies In Billions $3.72 billion '91 '92 '93 '94 '95 '96 '97 '98 '99 Sources: FDA Biomonitoring Research database; Parexel s Pharmaceutical R&D Statistical 6 Sourcebook 1999; Aculaunch; Washington Post Research

7 Overseas Clinical Trials Percentage of NDA Submissions Using Foreign Data % % Numbers of Foreign Human Subjects Participating in NDA Clinical Trials , ,000 Bamako

8 RC Trials in Africa Survey shows evidence of 1170 randomised controlled clinical trials conducted in Africa up to early Median sample size N=90; 79 had N> Most conducted in South Africa (565); Nigeria (98); Kenya (89); Gambia (56); Tanzania (50). Marked increase in no. of trials over time from less than 10 in 1965 to over 80 in Source: Isaakidis et al., BMJ, (2002) Bamako

9 RC Trials in Africa Source: Isaakidis et al., BMJ, (2002) Bamako

10 History of Research Ethics Largely, but not solely, driven by atrocities and abuses: Bamako

11 Nuremberg Trials 1948 Bamako

12 Bamako

13 Thalidomide 1962 Bamako

14 Wichita Jury Study 1955 Bamako

15 Jewish Memorial Hospital 1963 Bamako

16 Milgram s Obedience Studies 1960 s Bamako

17 Milgram cont d ( debriefing ) Bamako

18 Tuskegee Syphilis Study Bamako

19 Other scandals and debates: Willowbrook Childrens Hospital Hepatitis study (1950s) Tearoom Trade (Humphreys, 1970s) Zimbardo s Stanford prison simulations 1971 SA military studies on homosexuality (1970s) Wits breast cancer studies: Bezwoda (1990s) Stem cell debates (ongoing) Cloning (ongoing) PMTCT AZT trial (1990s) International clinical trials: Body hunting in developing countries Tsunami Research Concerns about HIV prevention trial results and closures Bamako

20 Guidance Documents and Formal Ethical Review The above led to the drafting of several international research ethics codes, largely for research with human participants. Legal requirements for formal ethical review of all human subjects research proposals followed now gaining global momentum: SA Health Act Bamako

21 Belmont Report 1979 Bamako

22 Georgetown Mantra Bamako

23 4 Key principles in research ethics NON-MALEFICENCE: Do no harm There should be no intentional injury or harm to participants as a result of participation; researchers are obligated not to deliberately harm participants BENEFICENCE: Minimize potential harms & maximize expected benefits of the research; Researchers should take active and positive steps to reduce possible harms to a minimum and to maximize anticipated benefits of the research In some research there may be no direct benefit for the participant, but benefits to society in terms of important knowledge Bamako

24 Key principles in research ethics cont d RESPECT FOR AUTONOMY: self-rule A person s freedom of thought & action should be respected and researchers must respect rights of participants who can make decisions to do so Researchers must take special measures to protect vulnerable participants whose freedom to make choices is limited, or those with no capacity to choose Bamako

25 Key principles in research ethics cont d JUSTICE: Fair balance of risks and benefits Those who stand to benefit from research must contribute to its risks and discomforts No group of persons should be asked to bear more than their fair share of the burdens of research; no group (e.g. impoverished) should be asked to bear research risks in order that others (e.g. the wealthy) enjoy benefits (new knowledge or products) No group should be deprived of fair access to the benefits of research; No class of person should be unfairly excluded from research (e.g. women) as this denies them relevant knowledge/ health interventions Bamako

26 US Guidance Documents Bamako

27 Declaration of Helsinki WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 29th WMA General Assembly, Tokyo, Japan, October th WMA General Assembly, Venice, Italy, October st WMA General Assembly, Hong Kong, September th WMA General Assembly, Somerset West, South Africa, October nd WMA General Assembly, Edinburgh, Scotland, October 2000 Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002 Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo : Currently being revised Bamako

28 CIOMS 1993; 2002 Bamako

29 UNESCO 2006 Bamako

30 Nuffield Council Reports 2002, 2005 Bamako

31 South African developments Wits (1966) & SA MRC (1977) were the first in SA to establish RECs and publish ethical guidelines HSRC has REC since 2003 New Health Act (61 of 2003) now requires review ( & written informed consent!) by an accredited REC for all research with human participants Bamako

32 SA National Guidance Bamako

33 SA Guidance Bamako

34 Resistance to Ethics Review There has been some resistance to mandatory ethical review, globally and locally. Some resistance is principled Academic freedom Dumbing down of innovative research designs Inappropriate p review criteria and processes Assumed universalism Biomedical origins of ethical review Some resistance is pragmatic Mission i creep Delays Structure of application forms Resistance to ethical review procedures should not be conflated with fundamental obligation of all researchers to be aware of the ethical obligations of researchers and to ensure that all research is conducted ethically. Bamako

35 What Makes Research Ethical? Eight (& 1) requirements for ethical research (Emanuel et al., 2004) Bamako

36 Advantages of this framework: It is pragmatic and researcher-friendly (i.e. not philosophically abstract) It is based on major international guidance documents It follows the sequence of research planning and conduct It is not reactive to a recent scandal Bamako

37 9 Requirements cont d 1 Community participation 2 Social value 3 Scientific validity & Integrity 4 Fair selection of participants 5 Favorable risk / benefit ratio 6 Independent & Competent Ethical Review 7 Adequate informed consent 8 Ongoing respect for dignity 9 Professional and scientific integrity Bamako

38 1. Community Participation Bamako

39 1. Community Participation cont d Bamako

40 2: Social Value Bamako

41 3. Scientific Validity Bamako

42 4: Fair Selection of Participants Bamako

43 5: Favourable Risk/Benefit Ratio Bamako

44 6: Independent Ethical Review Bamako

45 Formal Ethics Training of REC Chairpersons Chairper rsons No. of Graph 48: No. of Chairpersons Attended Formal Ethics Training prior to position after position HIV vaccine trial ethics 15 6 no yes Bamako

46 Formal Ethics Training of all REC No o. of Mem mbers Members Graph 49: Formal Training Attended by All Members of All RECs Prior Assuming After Assuming HIV Vaccine Position Position Trial Ethics Training no yes Bamako

47 AA P Dedicated Funds for REC? African AIDS Vaccine Programme yes no No. RECs A B C D E F G H I J K L Country Bamako

48 REC funding by region Graph 17: REC Funding at a Regional Level yes no % RECs Southern Africa East Africa West Africa Bamako

49 Perceived challenges to independence of RECs AA P African AIDS Vaccine Programme Pressure from sponsors: 28.1% Pressure from political powers: 12.5% Biased committee members: 94% 9.4% Lack of transparency of RECs: 6.3% Offers of money/ favour to RECs: 3.1% Unequal treatment of applicants in review: 3.1% Bamako

50 7: Informed Consent Bamako

51 8: Ongoing respect for participants p Bamako

52 9: Professional and scientific integrity Adherence to protocol Conflict of interest Data cleaning Fraud, fabrication, falsification Publication issues Authorships and acknowledgements IP issues Status of collaborators, contract workers in publications Bamako

53 Concluding Comments Ethics mainstreaming : In research proposal development and project planning Initial and ongoing training is needed: 1) For researchers as integral part of postgraduate education; and 2) for RECs Bamako

54 Research Ethics Training US NIH Fogarty International Center has taken the lead in funding: About 19 programmes since 2000 (est. US $ 19m); 2 in South Africa (SARETI, IRENSA) Wellcome Trust (Project & Centre Grants) EDCTP EU Funding for research ethics training is probably bl less than 0.01% 01% of research budgets globally!! Bamako

55 Main References Amdur, R. (2003) IRB member handbook. Sudbury: Jones & Bartlett. Beauchamp, T., & Childress, T. (2001). Principles of biomedical ethics (5 th ed.). NY: Oxford Cribb, R. (2004) Ethical regulation and humanities research in Australia: problems and consequences. Monash Bioethics Review, 23, Department of Health (2006). Guidelines for good practice in the conduct of clinical trials in human participants in South Africa. Pretoria: Author. Emanuel, E., Wendler, D., Killen, J., & Grady, C. (2004). What makes clinical research in developing countries ethical? The benchmarks of ethical research. Journal of Infectious Diseases,189, Fogarty International Center/US NIH (nd) Video series on Research ethics. Israel, M., & Hay, I. (2006). Research ethics for social scientists. London: Sage. Macklin, R. (2002) Unresolved issues in social science research. In F. Lolas, & L. Agar (Eds.) Interfaces between bioethics and the empirical social sciences (pp ). Buenos Aires: WHO/PAHO. Milford, C., Wassenaar, D.R., & Slack, C.M. (2006). Perceived capacity of selected African research ethics committees to review HIV vaccine trial protocols. IRB, 28(2), 1-9. Molyneux, C., Wassenaar, D., Peshu, N., & Marsh, K. (2005). Community voices on the notion and practice of informed consent for biomedical research. Social Science & Medicine, 61, National Research Council (2003) Protecting participants and facilitating social and behavioral sciences research. Washington, DC: National Academies Press. Perrey, C., Wassenaar, D.R., Gilchrist, S., & Ivanoff, B. (2008) Ethical issues in medical research in the developing world: Report on a meeting organised by Fondation Mérieux, Lyon. Developing World Bioethics. (Prepublication version available online) Republic of South Africa (2003) National Health Bill. Pretoria: Dept. of Health. Wassenaar, D.R. (2006) Ethical issues in social science research. In Terre Blanche, M., Durrheim, M., & Painter, D. (Eds.). Research in practice (2 nd ed.) pp Cape Town: Juta. Wassenaar, D.R., & Barsdorf, N. (2007). The ethical involvement of women in HIV vaccinetrials in Africa. Women & Health, 45 (1), Bamako

56 SARETI Personnel Prof Doug Wassenaar: Principal Investigator Prof Nhlanhla Mkhize: Deputy Co-Principal Investigator (KZN) Prof Mariana Kruger: Co-Principal Investigator (Pta) Dr Theresa Rossouw: Deputy Co-Principal Investigator (Pta) Prof Carel IJsselmuiden: Senior Executive Member Prof Linda Richter: Alternate Executive Member Ms Carla Pettit: Administrator (KZN) Ms Joyce Jakavula Administrator (Pta) Bamako