Legislating the Ethical Guidelines Indian Model

1. Legislating the Ethical GuidelinesIndian Model Dr Vasantha Muthuswamy Senior Deputy Director general Division of BMS Indian Council of Medical Research New Delhi - 110029 muthuswamyv@icmr.org.in

2. Indian Codes of Ethics, Guidelines & Regulations • 1000 BC : Caraka Samhita to 1-2 AD • 1947 : Nuremberg Code • 1956 : Code of Medical Ethics, MCI • 1964 : Helsinki Declaration • 1979 : Belmont Report (USA) • 1980 : Policy Statement on Ethical Considerations involved in research on Human Subjects • 1982/1992 : Proposed International Guidelines (WHO/CIOMS) • 1986 : EPA Act for r-DNA products • 1997 : Guidelines for Exchange of Human Biological Material for Biomedical Research Purposes • 2000 : Delhi Medical Council Regulations • 2000 : Revised ICMR Ethical guidelines • 2001 : Indian GCP Guidelines • 2004 : ART Guidelines

3. Guidelines in 1980 “Policy statement on ethical considerations involvement in research on human subjects” Prepared by ethics committee under the Chairmanship of Honourable Justice Shri H.R. Khanna

4. 1980 ICMR Guidelines • Ethics Committee • Informed consent • Clinical trials • Research on children, mentally disadvantaged, those with diminished autonomy • Traditional Medicine • Publications

5. PROCEDURE ADOPTEDA central ethics committee was constituted under chairmanship of justice Sh.M.N. Venkatachalia in the year 1996 • Ethical , Social, Legal dimensions • 27 members and Five Sub-committees of experts were set up for drawing up the guidelines in respective area . • Draft guidelines were prepared by these committees which were considered by CECHER in 1997 • A draft consultative document was prepared.

6. Major Areas Identified by the committee (1996) • Clinical evaluation of drug/devices/diagnostics/vaccines/herbal remedies • Epidemiological research • Human Genetic Research • Transplantation research including fetal tissue transplantation • Assisted Reproductive technologies

7. Ethical Guidelines for Biomedical Research on Human Subjects, 2000 All institutions in the country which carry out any form of biomedical research involving human beings should follow these guidelines in letter and spirit to protect safety and well being of all individuals. Guidelines at - http://www.icmr.nic.in It is mandatory that all proposals on biomedical research involving human subjects should be cleared by an appropriately constituted Institutional Ethics Committee (IEC)

8. Essentiality Voluntariness, informed consent and community agreement 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

9. Informed consent of subject Obligations of investigators Essential information for prospective research subjects Compensation of participation Selection of special group of research subjects Essential information on confidentiality for prospective research subjects Compensation from accidental injury International Collaborative Research Researcher’s relations with the media and publication practices General Issues

10. ETHICAL REVIEW MECHANISM Basic responsibilities of ECs Composition Review Procedures Decision Making Record Keeping Special Considerations

11. 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

12. Indian Acts/Order related to Health • Epidemic Diseases Act – 1897 • Red Cross Society (Allocation of Property Act) – 1936 • Drugs and Cosmetics Act – 1940 • Indian Nursing Council Act – 1947 • Dentists Act – 1948 • Pharmacy Act – 1948 • Employees State Insurance Act – 1948 • Medical Council of India Act – 1956, amended 2002 • Drugs and Magic Remedies Act (Objectionable advertisements), 1954 • Prevention of Cruelty to Animals Act – 1960 • Children Act – 1960 • Maternity Benefit Act – 1961 • Central Council for Indian Medicine Act – 1970

13. Indian Acts/Order related to Health (Contd.) • Medical Termination of Pregnancy Act – 1971 • Consumer Protection Act – 1986 • Environment Protection Act – 1986 • Mental Health Act – 1987 being amended • Rehabilitation Council of India Act - 1992 • Pre-natal Diagnostic Techniques (Regulation and Prevention of Misuse) Act -1994, amended 2002 • Organ Transplantation Act – 1994 • Persons with Disabilities (Equal Opportunity, Protection of Rights and Full Participation Act, 1995 • Pre-conception and Prenatal Diagnostic Techniques (Prohibition of sex selection) Act - 2003 • Guidelines for Exchange of Biological Material (MOH order, 1997) • Right to Information Act - 2005

14. Were these Acts and Guidelines protective enough for the participants in medical research?

15. Need for Laws Related to Biomedical and Behavioral Research • Inadequate regulations to stop violations of ethical norms • Availability of naive subjects and ignorant researchers • Inadequate knowledge of ethical review procedures when India is emerging as a global hub for clinical trials • Participation in research for access to drugs, payment/ compensation • Legislation in place for animal welfare in experimentation but not so for human research.

16. Role of Legislation • To decide what is mandatory / recommendatory • To instill a fear among those violating human rights • To provide access to justice • To upgrade norms of ethical research • To honour human rights obligations and rule of law • Justice ultimately is the function of law and not ethics of morality alone • Ethics still relevant since not all ethical guidelines can be legislated

17. Unethical Clinical Trials in India • Contraceptive trials • MNCs sponsored drug trials • Use of vulnerable groups - women, children, tribals etc • Pig Heart Transplantation • Fetal tissue transplantation

18. Recent Violation of Ethical Norms after release of revised ethical guidelines • 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

19. Regulation of Ethical Guidelines • Indirect • 2002 : Amendment to Drugs and Cosmetics Act • 2002 : Revised MCI Regulations • Direct • Proposed Bill

20. The Bill THE BIOMEDICAL RESEARCH ON HUMAN SUBJECTS (REGULATION, CONTROL AND SAFEGUARDS) BILL, 2005

21. Scope • Promote and regulate biomedical and behavioural research on human subjects to ensure safety and well being of the research subjects • Necessity to control and monitor the application of new technologies eg. stem cell research, therapeutic cloning, ART, Genomics etc. • To restrict unscrupulous clinical trials on unsuspecting patients

22. 4. Provide legislative power to the ICMR Ethical Guidelines formulated under the Chairmanship of Justice Shri M. N. Venkatachaliah, former Chief Justice and Chairman of National Human Rights Commission of India 5. Setting up of a National Biomedical Research Authority

23. The Bill envisages oversight mechanism • Creation of a National Biomedical Research Authority • Setting up of a National Ethics Committee on Human Research • Registration of Institutional Ethics Committees

24. “The Twin Pillars of Protection” in Biomedical research Rights and Welfare of Human Subjects Independent Review Informed Consent

25. Functions of National Biomedical Research Authority • To promote & ensure that research on human subjects is in accordance with the four basic ethical principles in the whole country • To grant recognition to institutions conducting biomedical research • Evaluate & monitor functioning of IECs throughout the country • To effect changes in ethical guidelines from time to time • To provide relief in cases of violation and exploitation

26. Authority Members • Chairperson – Eminent scientist appointed by Central Government • Vice-chairperson elected by members • Ex –officio members • Secretaries of Health, Family Welfare, Department of AYUSH, DST, DBT • Director Generals of ICMR, ICSSR, CSIR • Financial Advisor, Ministry of Health • Federal Government nominees • 6 eminent persons from Basic Sciences, Clinical Sciences, Community Health and Behavioral & Social Science • 2 persons representing NGO & social organisations • 1 eminent person from legal field • Member Secretary, Chief of Bioethics Cell, ICMR

27. Functions of the Authority • take steps ensuring biomedical research in accordance with four basic principles, namely respect for persons, beneficence, non-maleficence and justice • The Authority may identify from time to time the basic ethical principles • Evaluate and monitor the performance of institutional Ethics Review Committees • Recommend to the Central Government the specific guidelines

28. Functions of the Authority (contd.) • Evolve suitable performance appraisal systems, norms and mechanisms • Delineate between biomedical or behavioral research • Integrate medical research with professional care • Assess from time to time vulnerability of certain sectors • Determine nature & definition of informed consent • Determine the potential conflict of interest • Promote disclosure on the ethical, social, legal and moral implication of advances in biomedical and behavioral research

29. Chapters in the Bill • Chapter I - short title, extent & commencement, and definitions • Chapter II - Provision for the establishment of the Biomedical Research on Human Subjects Regulatory Authority • Chapter III - functions of Authority • Chapter IV – provisions for finance, accounts & audit of the authority • Chapter V – Issue of licenses, fees, cancellation & renewal of licenses • Chapter VI – Ethics review Committees,National ethics committee • Chapter VII – Conditions for Subject participation : special groups, women & children, vulnerable groups • Chapter VIII – Clinical Research

30. Chapters in the Bill (Contd.) • Chapter IX – Research in Epidemiology • Chapters X – Research in Human genetics & Genomics • Chapter XI – Research in Assisted Reproductive Technology • Chapters XII – Reserach in Transplantation of Human Organs & Tissues • Chapters XIII – Offences • Chapters XIV – Control by Central Government • Chapters XV - Miscellaneous

31. NECHR will recommend the following to the authority • To ensure that research by the recognised institutions is beneficial to the human subjects • To identify required changes in various schedules • To suggest changes in monitoring of the performance of IECs & the various procedures • To suggest procedural changes of biomedical & behavioural research • To review proposals with far reaching national & international consequences

32. Rules & Regulations to be placed before the Parliament: Schedules in the Bill • Schedule A - General Principles for conducting biomedical research on human subjects • Schedule B - Guidelines for research in clinical evaluation of drugs, vaccines, devices, diagnostic and herbal remedies (includes principles of Drugs & Cosmetics Act & Indian GCP guidelines) • Schedule C - Guidelines for research on human subjects in epidemiological studies

33. Schedules in the Bill (Contd.) • Schedule D - Guidelines for research in human genetics and genomics (includes genetics and genomics guidelines of DBT as one common code) • Schedule E - Guidelines for research in assisted reproductive technology • Schedule F - Guidelines for research in transplantation of human organs and tissues

34. Offences • Powers of Authority to give directions………...shall be liable on conviction to imprisonment which may extend to six months or to a fine which may extend to ten thousand rupees or with both. • Penalty for misrepresentation …..punished with imprisonment for a term which may extend to six months, or with fine which may extend to then thousand rupees, or with both. • Penalty for breach of confidentiality and privacy…………... punished with imprisonment which may extend to six months or a fine which extend to ten thousand rupees or with both. • offence or contravention committed outside India

35. Current Status • Draft legislation ready for placing before the Parliament for notification after vetting by the Law department • Wide Public Consultation • Regional and National Debates • Will provide legal support to the ethical guidelines • Implementation

36. THANK YOU