1. Research ethics & ethical clearance

2. Ethics Ethics a set of principles that determine the a set of principles that determine the right and acceptable conduct right and acceptable conduct Hippocratic Oath Hippocratic Oath

3. Main principles of the Hippocratic Oath are summarized as do no harm do no harm not to assist suicide or administer euthanasia not to assist suicide or administer euthanasia not to cause abortion not to cause abortion to refer patients for specialized treatment to refer patients for specialized treatment not to abuse professional relationships, especially for sexual motives not to abuse professional relationships, especially for sexual motives to maintain patient’s confidence to maintain patient’s confidence Do not share patient information Do not share patient information

4. Research ethics The application of moral rules and professional codes of conduct to the collection, analysis, reporting, and publication of information about research subjects, in particular active acceptance of subjects' right to privacy, confidentiality, and informed consent.

5. How did research ethics evolve?

6. Tuskegee Study ( Alabama) 1932 -1972 399 poor and mostly illiterate Negro males suffering from Syphilis were studied to observe the natural progression of the disease 399 poor and mostly illiterate Negro males suffering from Syphilis were studied to observe the natural progression of the disease The subjects were not told they had syphilis and consequently they went into infecting many of their wives, which resulted in 19 of their children being born with congenital syphilis. The subjects were not told they had syphilis and consequently they went into infecting many of their wives, which resulted in 19 of their children being born with congenital syphilis. by 1947 penicillin had become the standard treatment for syphilis. However, the treatment was withheld. by 1947 penicillin had become the standard treatment for syphilis. However, the treatment was withheld. Eventually the study was leaked to the press and the program was terminated.

7. Nazi human experimentation early 1940’s Experiments carried out on large numbers of prisoners in concentrated camps by the German Nazi regime during World War II Experiments carried out on large numbers of prisoners in concentrated camps by the German Nazi regime during World War II They were forced into participating They were forced into participating Typically, the experiments resulted in death, disfigurement or permanent disability of the subjects Typically, the experiments resulted in death, disfigurement or permanent disability of the subjects

8. Nazi human experimentation Freezing/hypothermia experiment - 1941 Victims troops; healthy Jews/Russians They were usually stripped naked and prepared for the experiment A insulated probe was inserted into the rectum to measured the drop in the body temperature The victim put into an air force uniform, was then placed in the tub of cold water and started to freeze Results: most victims lost consciousness and died (about a 100) when the body temperature dropped to 77 °F (25 °C).

9. Nazi human experimentation to test for immunization and treatment of malaria. Prisoners were infected by mosquitoes or by injections of extracts of the mucous glands of female mosquitoes. About a half died of the disease and subsequent complications. Malaria experiments (1942-1945) – conducted on over 1200 prisoners to test for immunization and treatment of malaria. Prisoners were infected by mosquitoes or by injections of extracts of the mucous glands of female mosquitoes. About a half died of the disease and subsequent complications. Mustard gas experiments (1939-1945) - subjects were deliberately exposed to mustard gas which inflicted severe chemical burns. Then they were tested to find the most effective treatment for the mustard gas burns. Mustard gas experiments (1939-1945) - subjects were deliberately exposed to mustard gas which inflicted severe chemical burns. Then they were tested to find the most effective treatment for the mustard gas burns. Wounds inflicted on the subjects were infected with bacteria, such as Streptococcus, gas gangrene and tetanus. Blood circulation to these wounds was interrupted to create a condition similar to that of a battlefield wound. Infection was aggravated by forcing wood shavings and ground glass into the wounds. The infection was treated with sulfonamide and other drugs to determine their effectiveness. Sulfonamide experiments (1942-1943) - Wounds inflicted on the subjects were infected with bacteria, such as Streptococcus, gas gangrene and tetanus. Blood circulation to these wounds was interrupted to create a condition similar to that of a battlefield wound. Infection was aggravated by forcing wood shavings and ground glass into the wounds. The infection was treated with sulfonamide and other drugs to determine their effectiveness.

10. Aftermath of the experimentation Many of the subjects died, many others were murdered after the tests were completed to carryout a post mortem. Those who survived were often left mutilated, suffering permanent disability, weakened bodies, and mental duress. Many of the subjects died, many others were murdered after the tests were completed to carryout a post mortem. Those who survived were often left mutilated, suffering permanent disability, weakened bodies, and mental duress. On August 19, 1947, the doctors captured by Allied forces were put on trial in USA – Doctor’s trial. At the trial, several of the doctors argued in their defense that there was no international law regarding medical experimentation. On August 19, 1947, the doctors captured by Allied forces were put on trial in USA – Doctor’s trial. At the trial, several of the doctors argued in their defense that there was no international law regarding medical experimentation. This led to the development of the Nuremberg Code of medical ethics. This led to the development of the Nuremberg Code of medical ethics.

11. Nuremberg Code - 1949 The code calls for standards such as, voluntary consent of human subjects voluntary consent of human subjects to recognize that the expected benefits must outweigh the risks, and that unnecessary pain and suffering must be avoided. to recognize that the expected benefits must outweigh the risks, and that unnecessary pain and suffering must be avoided. doctors should avoid actions that injure human patients. doctors should avoid actions that injure human patients. Nuremberg code was updated by WHO as the Declaration of Helsinki (1964) Nuremberg code was updated by WHO as the Declaration of Helsinki (1964)

12. Aftermath In 1972 with the termination of the In 1972 with the termination of the Tuskegee Study The, National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the National Research Act were established. The, National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the National Research Act were established. The act required the establishment of Institutional Review Boards (IRBs) The act required the establishment of Institutional Review Boards (IRBs) Special consideration was given to ethnic minorities and vulnerable groups in the design of clinical studies. Special consideration was given to ethnic minorities and vulnerable groups in the design of clinical studies.

13. Codes and Guidelines Nuremberg Code (1949) Nuremberg Code (1949) Declaration Of Helsinki (1964- 2000) Declaration Of Helsinki (1964- 2000) The Belmont Report (1979) The Belmont Report (1979) CIOMS/WHO International Guidelines (1993, 2002) CIOMS/WHO International Guidelines (1993, 2002) ICH/GCP-International Conference on Harmonization- Good Clinical Practice (1996) ICH/GCP-International Conference on Harmonization- Good Clinical Practice (1996)

14. Values that commonly apply to medical ethics Values that commonly apply to medical ethics Autonomy - right to refuse or choose their treatment Autonomy - right to refuse or choose their treatment Autonomy Beneficence – the practitioner should act in the best interest of the patient Beneficence – the practitioner should act in the best interest of the patient Beneficence Non-maleficence - do no harm Non-maleficence - do no harm Non-maleficence Justice - concerns the distribution of scarce health resources, and the decision of who gets what treatment (fairness and equality). Justice - concerns the distribution of scarce health resources, and the decision of who gets what treatment (fairness and equality). Justice Dignity - the patient (and the person treating the patient) have the right to dignity. Dignity - the patient (and the person treating the patient) have the right to dignity. Dignity Truthfulness and honesty - the concept of informed consent Truthfulness and honesty - the concept of informed consent Truthfulnesshonesty Truthfulnesshonesty

15. The 7 principles that makes clinical research ethical

16. 1. Social value Is this research of any value?? Is this research of any value??  why do this research?  if not done would the information be missed?  can the results be generalized? Research has no value when, results unlikely to be disseminated results unlikely to be disseminated interventions could never be practically implemented interventions could never be practically implemented

17. 2. Is this research scientifically valid?

18. for research to be scientifically valid, clear scientific objectives clear scientific objectives design in relation to objectives design in relation to objectives methodology reliable – produce valid data methodology reliable – produce valid data practically feasible practically feasible principal investigators and the other principal investigators and the other research personnel should be competent. research personnel should be competent. A socially, clinically, or scientifically useful research question that will generate useful new knowledge about human health Research must be conducted in a methodologically rigorous manner.

19. 3. Fair subject selection  Justice  subject selection – Selection of subjects for reasons of science, related to the purpose of the study, not because they are readily available, vulnerable, or otherwise easily exploited, or are favored. - select subjects to minimize risks and maximize benefits - select subjects to minimize risks and maximize benefits - have clear inclusion/exclusion criteria - have clear inclusion/exclusion criteria

20. 4. Favorable Risk-Benefit Ratio for research to be ethical, any risks must be balanced by the benefits to subjects

21. 5. Independent Review Minimize conflict of interest Public Accountability Independent review of clinical research ensures the public that investigator biases have not distorted the approach, that ethical requirements have been fulfilled, and that subjects will not be exploited. Independent review of clinical research ensures the public that investigator biases have not distorted the approach, that ethical requirements have been fulfilled, and that subjects will not be exploited.

22. 6. Informed consent of subject

23. What is informed consent ? Respect for Persons based on understanding the objectives, risks, benefits, and alternatives of the research. voluntary decision taken by an individual to participate in research based on understanding the objectives, risks, benefits, and alternatives of the research. the principal investigator has responsibility to obtain voluntary informed consent (either verbal or written) from all prospective participants or the principal investigator has responsibility to obtain voluntary informed consent (either verbal or written) from all prospective participants or in the case of individuals who are not capable of giving informed consent, the permission of their legally authorized guardians (proxy consent). in the case of individuals who are not capable of giving informed consent, the permission of their legally authorized guardians (proxy consent).

24. Components of informed consent information sheet information sheet seek consent only after the participant has seek consent only after the participant has received and adequately understood all received and adequately understood all necessary information and the consequences necessary information and the consequences of participation as given in the information sheet of participation as given in the information sheet if written, the consent form has to be in all three if written, the consent form has to be in all three languages languages if written, consent should be obtained by if written, consent should be obtained by signing on a consent form signing on a consent form

25. Informed consent contin.. Information sheet should contain Self introduction – from where & who you are; Self introduction – from where & who you are; purpose of the research; purpose of the research; description of benefits from participating; description of benefits from participating; description of risks from participating; description of risks from participating; details of time commitment required; details of time commitment required; details of any remuneration; details of any remuneration; plans to ensure the confidentiality of data; plans to ensure the confidentiality of data; details about the right to withdraw at any time for any reason; details about the right to withdraw at any time for any reason; information about how to communicate a decision to withdraw from the study; information about how to communicate a decision to withdraw from the study; name(s) of investigator(s) contact details. name(s) of investigator(s) contact details. The wording should suit the individual’s level of understanding

26. 7. Respect for enrolled subjects Beneficence and Respect for Persons  should be concerned about the wellbeing of the subjects as the study proceeds  assure confidentiality of information  permitting them to change their mind – withdraw without penalty  informed of new information – new risks /treatment  share results of subjects  ensure privacy  maintain anonymity  minimise disruption to work

27. As for research ethics, where do we stand today? Faculty of Medicine, University of Colombo was the first institution in Sri Lanka to establish an institutional Ethics Review Committee, in 1981. Faculty of Medicine, University of Colombo was the first institution in Sri Lanka to establish an institutional Ethics Review Committee, in 1981. In 1991, NARESA drew up a draft code for scientific research, animal experimentation, biomedical research on humans and social sciences research. In 1991, NARESA drew up a draft code for scientific research, animal experimentation, biomedical research on humans and social sciences research. Since then several organisations such as, SLMA, SLAAS, Min. of Health, NASTEC, NSF, SLMC have set up their own institutional Ethics Review Committee. Since then several organisations such as, SLMA, SLAAS, Min. of Health, NASTEC, NSF, SLMC have set up their own institutional Ethics Review Committee. Ethical review is mandatory for the presentation and publication of research. Ethical review is mandatory for the presentation and publication of research.