Introduction to Ethics - Principles of Ethics

1. Introduction to Ethics - Principles of Ethics Nandini K. Kumar Former Dy Director General Sr. Grade Co-Investigator NIH Project on Bioethics National Institute of Epidemiology Chennai nandkku@gmail.com

2. ETHICSMoral, Ethical & Legal aspects Internal - Moral code of conduct Guidelines Political decision - Code of Ethics Legislation by State - External

3. Principles in Indian Traditional Systems of Medicine • Ayurveda • Siddha • Unani Information aquired for benefit of patients

4. OLDER CODES OF MEDICAL ETHICS • 10th Century BC – 200 AD : Caraka Samhita (written code) • 4th Century BC : Hippocratic Oath

5. “Primum non nocere” (first do no harm)

6. Visesa dharma Sadharana dharma • Universal • For all on all occasions • Honesty, compassion, respecting others, kindness, humility etc • Obligations based on cultural context, the institutional affiliation, the family background, the social status, the gender and the stage in life • Professional obligations • Swadharma and paradharma

7. The cardinal virtues Isavasyam dam sarvam Yat kincha jagatyam jagat Tene tyktena bhunjita Ma gritha kasya sidhanam Isavasyopanishad • Truth, non-violence, non-stealing and non-possession

8. Greatest good for greatest number (means to an end) Utilitarianism (Teleontology) Always act right or do good (means are ends in themselves) Kantianism (Deontology) Normative Ethical Theories Circumstances Consequences

9. Virtue Ethics • Depends on the character of individual • Practical virtues can only be steadied • through habit • a conscious effort to inculcate them in our daily actions until they become a part of one’s very character

10. Code of conduct/ Ethical Guidelines for physicians and / Researchers • 3000 BC - Siddha guidelines • 1000 B.C. - Caraka Samhita to 1-2 AD • 4 – 5thth C BC - Hippocratic oath • 1-2 AD - Hammurabi Code • 1847 - AMA code of ethics, first national • 1865 - Claude Bernard ‘Introduction Experimental Medicine’ • 1897 - Code of medical Ethics, AMA • 1898 - German Ethics of Science & Medicine • 1933 - Guidelines by Reich Government

11. Nazi Medical Experiments in WW II Concentration Camps

12. Romanian Gypsy in Potable Seawater, Hypothermia & High Altitude Experiments at Dachau

13. Twin Studies in Auschwitz Dr. Josef Mengele

14. Eva Mozes KorFounder CANDLES Holocaust Museum • Mrs. Mozes Kor was born January 31, 1934 in Romania. In March of 1944, she and her family were told by gendarmes to gather belongings because they were going to be relocated. They were deported to Auschwitz Concentration Camp. • Mrs. Mozes Kor founded CANDLES, an organization devoted to the twins who survived the horrible experiments of Dr. Mengele. She located 122 survivors of Mengele’s experiments, living in ten countries and four continents.  She later opened the CANDLES Holocaust Museum and Education Centre. • Today Mrs. Mozes Kor devotes much of her time to speaking about what happened to her and to serving the Museum.

15. Deliberate Phosphorous Burn to Test Medications at Buchenwald

16. Sterilization experiments

17. Dr. Leo Alexander with Survivor of Experiments at Ravensbrueck Defendants and Defense Counsel 15 of 23 guilty, 7 hanged, 5 life sentences

18. Codes of Medical Ethics / Guidelines • 1947 : Nuremberg Code • 1948 : Universal Declaration of Human Rights Geneva • 1956 : Code of Medical Ethics, MCI • 1964 : WHA, Helsinki Declaration

19. Nuremberg Code • Informed Consent • Termination of study • Participant • Investigator

20. Declaration of Helsinki 1964 • Need for a clear experimental protocol • To be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or any other kind of undue influence • What to submit for review

21. Landmark Article on U.S. Abuses Henry Beecher, NEJM, 1966

22. Tuskegee Syphilis Study American medical research project conducted by the U.S. Public Health Service from 1932 to 1972, examined the natural course of untreated syphilis in African-American men.

23. Tuskegee Syphilis StudyLetter to patients from Macon County Health Department REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT: BE SURE TO MEET THE NURSE

24. Tuskegee Syphilis Study Results: • 28 deaths, • 100 cases of disability, • 19 cases of congenital syphilis Lack of informed consent, putting participants and their families to risk, exploitation of vulnerable population, deception, withholding information, no benefit to participants

25. Apology from Clinton - 1997 "What was done cannot be undone, but we can end the silence ... We can stop turning our heads away. We can look at you in the eye, and finally say, on behalf of the American people, what the United States government did was shameful and I am sorry." $ 7 b compensation

26. The Belmont Report 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

27. Ethical Principles in Modern Medicine Autonomy Beneficence Non-maleficence Justice

29. Radiation experiments Jewish Chronic Diseases Study Pfizer meningitis study Other violations no full disclosure, coercion/ undue pressure, vulnerable subjects

30. Guatemala Trial (1946 - 48) – US Public Health Project • Indiana prisoners • Gautemala1300 on trial, 83 died • Prisoners, soldiers, sex workers, mentally incapacitated, orphans used • Transmission of Syphilis through sexual and direct contact • Effect of Penicillin studied • Dr. Cutler went to Tuskegee after this • President Obama’s Bioethics Commission • - In-depth study of the case • International panel set up • Report will be released today (13.9.2011)

31. Codes of Medical Ethics / Guidelines • 1945 : Nuremberg Code • 1964 : Helsinki Declaration • 1979 : Belmont Report,USA • 1980 : ICMR’sPolicy Statement, • 1993 -95 : Genetics, Human tissue, Xeno - transplantation (Nuffield Council, UK) • 1982, 1991, 1993 : The WHO / CIOMS guidelines • 1996 : ICH GCP Guidelines • 2008 : Last Revised Helsinki Declaration

32. Guidelines (contd.) • 2000 : Revised ICMR guidelines ‘Ethical Guidelines for Biomedical Research on Human Subjects’ • 2000 : Delhi Medical Council Regulations • 2002 : Indian Medical Council Act amendment • 2001 : NBAC Report – Developing countries • 2001 : Indian GCP Guidelines • 2002 : Nuffield Council – Developing Countries • 2002 : CIOMS - Developing Countries • 2005 : Amendment of Schedule Y of Drugs & Cosmetics Act, 1940 • 2006 : 2nd rev. ICMR’s ethical guidelines • 2007 : Guidelines for Stem cell Research & Therapy

33. The Bill THE BIOMEDICAL RESEARCH ON HUMAN PARTICIPANTS (PROMOTION AND REGULATION) BILL, 2007 Title changed to THE BIOMEDICAL (AND HEALTH) RESEARCH INVOLVING HUMAN PARTICIPANT (REGULATION OF ETHICAL, LEGAL, SOCIAL ASPECTS) BILL Legislation in 2011? Ethical Guidelines

34. US - Compliance with the following procedural standards: • 45 CFR 46 and all of its subparts (A,B,C,D) • 45 CFR 46, subpart A (Common Rule) • 21 CFR 50 and 21 CFR 56 • CIOMS International Ethical Guidelines • ICH-GCP-E6 Sections 1 through 4 • Canadian Tri-Council Policy • Indian Council of Medical Research • Other(please submit copy to OHRP with this Assurance)

35. Dimensions in Practice and Research Human Rights Scientific & Technical Content Ethical aspects

36. Violation of Ethical Norms during & after release of ethical guidelines, 2000 • Pig Heart Transplantation • John Hopkins – RCC Collaboration • VEGF trial in a private hospital in Delhi • Genetics Research on vulnerable population (tribals) funded by NIH, EU & published in American Journal without Indian Collaborator or Govt. consent • Anti-cancer drug ‘letrozole’ as fertility agent without DCGI’s clearance – off label use • Erythromycin trial for contraception • HPV Vaccine study

37. Essentiality Voluntariness, informed consent and community agreement (ECs shall decide about waiver) Non-exploitation Privacy and confidentiality Precaution and risk minimisation Professional competence Accountability and transparency Maximisation of the public interest Institutional arrangements Public domain Totality of responsibility Compliance General Principles

38. Informed consent of subject – Fresh /re-consent Waiver of consent Obligations of investigators Essential information for prospective research participants Compensation of participation Conflict of interest Selection of special group of research participants Selection of special groups as researchparticipants Essential information on confidentiality for prospective research participants Compensation from accidental injury Post – trial access International Collaborative Research/ Assistance in Biomedical / Health Research Researcher’s relations with the media and publication practices General Issues

39. Specific Principles • Clinical Trials of Drugs, Devices, Vaccines, Diagnostic agents, Herbal Drugs • Epidemiological Studies • Human Genetics Research • Transplantation Research including Fetal tissue and Xeno- transplantation • Assisted Reproductive Technologies

40. Issues in Clinical trials • DRUG TRIALS – special considerations increased • Phases of clinical trials – Combined Phase I & II & special studies • Multicentric trials - special concerns increased • Contraceptive trials • Monitoring ADRs / Aes – text changed • Vaccine trials including r-DNA and combination vaccines - special concerns increased • Devices/ Surgical procedures – text changed • Herbal remedies – text changed

41. Epidemiological Studies • Definition/Types of studies • General Principles • Specific Principles - Informed consent –individuals & communities, inducements, risks, benefits, ethical review procedures, conflict of interest – community participation • Privacy/ Confidentiality • Programme Evaluation

42. General issues Pedigree studies Privacy/confidentiality Genetic screening Therapeutic trials including Gene therapy Human Genome Project DNA and cell line Banking/ repository - Excerpt from Draft Guidelines on Biobanking added DNA diagnosis Pre- natal diagnosis Assisted reproductive technologies – removed Human Genome Diversity - removed Human Genetics Research

43. Guidelines for Stem Cell Research And Therapy Department of Biotechnology Indian Council of Medical Research 2007 Organ Transplantation • Definitions • Live donor transplants • Cadaver donor transplants • Research on recipients • Fetal tissue transplantation • Xeno-transplantation • Transplantation for cosmetic purposes • Stem cell research & therapy - Excerpt from National Guidelines added

44. Assisted Reproductive Technologies • Definitions • Informed consent • Privacy/confidentiality • Selection of donor • Legitimacy of the child • Surrogate motherhood • Research on embryos/spare embryos Excerpt from National Guidelines added

45. Guidelines for Stem Cell Research And Therapy Department of Biotechnology Indian Council of Medical Research 2007 Guidelines • Draft Guidelines • Mental Health • Dataset protection • Disaster situations Ethical Guidelines for Social Science Research (2000)

46. THANK YOU