1. Ethics In Scientific Research 12 th Feb 2014 Dr Fergal Grace

2. Session Aims Introduce the Key Events and Historical Background to Research Ethics Develop understanding for the Principles of Ethical Research Outline the role of Ethics Committee/Institutional Review Boards (IRB) Completing the UWS Standard Ethics Application Form. – What should you include – How much information is needed – Risk assessment – Appendices Post Approval Changes to Project. Dr Fergal Grace

3. Ethics- Historical Perspective Trigger Event Response Progress Dr Fergal Grace

4. Nazi Experiments during WW2 Dachau 1942-1944high altitude experiments, tested limits of exposure, forced drinking of seawater. Buchenwald and Ravensbruck (1941-45) Burns, Mustard Gas, battlefield injuries Dachau, Buchenwald, Sachsenhausen (1941-45) Infectious diseases Auschwitz Buchenwald and Ravensbruck (1941-45) eugenics & lethal experiments Dr Fergal Grace

5. Nuremberg Trials (1947) During the Nuremberg War Crimes Trials, 23 defendants included 20 doctors. Yielded 16 guilty verdicts and 7 death penalties. First major public exposition of doctors becoming instruments in unethical practice. Part of verdict…Gave rise to the Nuremberg code (1947) relating to; - voluntary consent - benefits outweigh risks - ability for participants to terminate participation Dr Fergal Grace

6. 10 Principles of Ethical Research 1.The voluntary consent of the human subject is absolutely essential. 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. 3. The experiment should be so designed and based on the results of animal experimentation and knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment. 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. 5. No experiment should be conducted where there is an a priori reason to believe that death or disability injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects. 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. 7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. 8. The experiment should be conducted only by scientifically qualified persons. 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible. 10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject. Dr Fergal Grace

7. Declaration of Helsinki (1964) Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and as revised by the World Medical Assembly in Tokyo, Japan in 1975, in Venice, Italy in 1983, and in Hong Kong in 1989 and Somerset West, Republic of South Africa, October 1996; and 52 nd WMA, Edinburgh, Scotland 2000. “ Concern for the interests of the subject must always prevail over the interests of science and society. ” Dr Fergal Grace

8. Tuskegee Syphilis Study (1932-1972) Recruited to receive ‘free treatment’ Never told they were a research participant Aim of research – would a person be “better off” not receiving treatment for syphilis Never told they had syphilis Therefore never advised syphilis was contagious Never given antibiotics when they became available in 1947 Dr Fergal Grace

9. Tuskegee Syphilis Study (1932-1972) Considerations: Were the participants fully informed about the aim of the research? Would they be at risk physically or mentally? Was the research necessary following the introduction of penicillin in 1947? Were they denied their rights? Dr Fergal Grace

10. Milgram – Obedience to Authority Study (1963) Advised research objective = Effects of Punishment on Learning Role of Learner Role of Teacher Questions & Answer Session Shock treatment Milgram, S. (1963). Behavioral study of obedience. Journal of Abnormal and Social Psychology, 67, 371–378. Dr Fergal Grace

11. Results: All 40 participants (teachers) gave ‘electric shocks’ 5/40 stopped at shocks of 300 volts (Intense Shock) after the Learner pounded the wall 14 gave shocks of 450 volts 3 participants had seizures Others sweated, laughed, bit their fingers Milgram – Obedience to Authority Study (1963) Milgram, S. (1963). Behavioral study of obedience. Journal of Abnormal and Social Psychology, 67, 371–378. Dr Fergal Grace

12. Questions Did the participants consent to the actual research taking place – obedience of an authority figure? Did they need to be deceived regarding shock treatments Filmed without consent –should they have been informed? Was there physical or mental risk? Could they refuse to go on? Milgram – Obedience to Authority Study (1963) Milgram, S. (1963). Behavioral study of obedience. Journal of Abnormal and Social Psychology, 67, 371–378. Dr Fergal Grace

13. Beecher NEJM Article (1966) “ Ethics and clinical research ” Henry K. Beecher 22 published medical studies presenting risk to subjects without their knowledge or expected benefir Case where patients infused with live cancer cells had been told they were receiving "some cells" without specifying that they were cancer. "ultimately contributing to the impetus for the first NIH and FDA regulations." Beecher HK. Ethics and clinical research. N Engl J Med 1966; 274: 1354-60. Dr Fergal Grace

14. Beecher NEJM Article (1966) “ Ethics and clinical research ” Henry K. Beecher Published in some of the most prestigious journals and conducted at some of the most prestigious institutions He worked both in defining the rules and conditions for informed consent and in establishing institutional research boards as additional layer of oversight "ultimately contributing to the impetus for the first NIH and FDA regulations." Dr Fergal Grace

15. Laud Humphries Tearoom (1970) PhD Thesis “Tearoom trade: a study of homosexual encounters in public places” Homosexuality was a crime in 1960’s Masqueraded as a Voyeur, in cases taking registration plate details from cars and following men home Over 100 observations, More than 50% were heterosexual Dr Fergal Grace

16. The Belmont Report (1979) Ethical Principles and Guidelines for the Protection of Human Subjects of Research The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research April 18, 1979 Dr Fergal Grace

17. The Belmont Report (1979) Basic Principles: Respect for Persons – Individual autonomy – Protection of individuals with reduced autonomy Beneficence – Maximize benefits and minimize harms Justice – Equitable distribution of research costs and benefits Dr Fergal Grace

18. The Death of Ellen Roche (2001) 24 year old volunteer in asthma study – died from inhaling haxamethonium medication which was an outdated treatment for high blood pressure She was a technician at John Hopkins Asthma and Allergy Center who volunteers to have a provoked mild asthma attack Died one month into the study NIH and IRB both approved the study but hexamethonium was not approved as a drug by FDA. Federal investigation found serious problems with the IRB and all federally funded research was suspended. Universities Worldwide Dr Fergal Grace

19. key principles of ethical research Research should be designed, reviewed and undertaken to ensure integrity and quality Research staff and subjects must be informed fully about the purpose, methods and intended possible uses of the research, what their participation in the research entails and what risks, if any, are involved. The confidentiality of information supplied by research subjects and the anonymity of respondents must be respected Research participants must participate in a voluntary way, free from any coercion Harm to research participants must be avoided The independence of research must be clear, and any conflicts of interest or partiality must be explicit Source: ESRC Research Ethics Framework www.esrc.ac.ukwww.esrc.ac.uk Dr Fergal Grace

20. Institutional Review Board (IRB)/ Ethics Committee Matrix BENEFICENCEJUSTICE RESPECT FOR PERSONS Protection of subjects (especially vulnerable populations) Informed consent Surrogate consent Assent Risk/Benefit Analysis Experimental Design Qualifications of PI Subject selection Inclusion/exclusion Recruitment Dr Fergal Grace

21. Completing the UWS Application for Ethical Approval Confirmed with Director of Studies – Project Design What data do you plan to collect and how? – If your data involves human participants? Who are they? How will they be recruited? How will you obtain access to your participants? How will you inform the participants about what you plan to do to them? If it is a sensitive issue how will attempt to minimise embarrassment? How will you make it clear that they can withdraw at any time? Will you provide information on your findings to your participants? Are there any features of your proposal which may raise ethical concerns that should be flagged at the outset? Dr Fergal Grace

25. Risk assessment Research is by nature uncertain. The researcher may not be fully aware of the possible hazards involved in the proposed research. For example in the early stages of the development of new drugs their long term effects may not be known. In these circumstances the participant may not be fully informed of potential risks. Dr Fergal Grace

26. Protection of Vulnerable Groups (PVG) Dr Fergal Grace

27. The Consent Process Informed consent is not a single event or just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject. The basic elements of the consent process include: full disclosure of the nature of the research and the subject's participation, adequate comprehension on the part of the potential subjects, and the subject's voluntary choice to participate. Dr Fergal Grace

28. The Process of Obtaining Consent 1.Identify participant population 2.Produce information sheet and consent document 3.Obtain permission from school’s ethics committee 4.Present research information to participant and discuss its contents – indicating that withdrawal at any time is possible 5.Answer participants questions 6.Give a copy of the consent document 7.Allow the participant time to consider 8.Meet participant and discuss documents, to answer any more questions and assess participants understanding 9.Obtain appropriate signed consent 10.Start research Dr Fergal Grace

29. Information Sheet & Consent Form The Aim or Purpose - Brief description of the study. Procedures - Brief description of how you intend to collect data (what they have to do)! Benefits - What would the benefits be to them and or/you the researcher. Risks - Identify any risks, such as the exercise will be strenuous. Queries - You are happy to answer any queries. Withdrawal - Inform them they are free to withdraw at any time. Confidentiality – Any data will be recorded anonymously. Consent - I ………… Print Name ………. have understood the procedures for testing and have had everything explained to my satisfaction agree to participate. Participant Signature Researcher Signature ……………………………….. ……………………………………. Date ………………….. Dr Fergal Grace

30. Conflict of Interest Dr Fergal Grace

31. Reference Material http://publicationethics.org/files/Full%20set% 20of%20flowcharts.pdf http://publicationethics.org/files/Full%20set% 20of%20flowcharts.pdf Milgram, S. (1963). Behavioral study of obedience. Journal of Abnormal and Social Psychology, 67, 371–378. Beecher HK. Ethics and clinical research. N Engl J Med 1966; 274: 1354-60. Dr Fergal Grace