History of Evolution of Ethical Guidelines and Clinical Research Regulations

Transcription

1 History of Evolution of Ethical Guidelines and Clinical Research Regulations Dr P Paul Kumaran MBBS, BA (Psychology), MPH Scientist E [Deputy Director Medical] National Institute for Research in Tuberculosis (ICMR) Madurai, Tamil Nadu, India ppaulkumaran@nirt.res.in

2 Can you tell me, Socrates, whether virtue is acquired by teaching or by practice, or if neither, then whether it comes to man by nature, or in what other way? I do not even know what virtue is, much less how it is acquired Ref: Plato - Dialogues Socrates (469/ BCE) was a Greek philosopher and is considered the father of western philosophy; Plato was his most famous student

3 Synonym: Definition: Context: Relevance: Ethics: What is it? Moral Philosophy Systematizing, defending, and recommending concepts of right and wrong behaviour Geographic & Cultural Medicine, Public Health & Research It is the science of morality grammar of one s behaviour affecting others (Universal fact that all human beings are vulnerable, can suffer from harm and cause harm) Humans being fallible educating is not guaranteed success

4 30 th Century BC Siddha 10 th Century BC 200 AD: Caraka saṃhitā (written code on Ayurveda - Indian traditional medicine) 4 th Century BC: Hippocratic Oath 1-2 nd Century AD: Code of Hammurabi (Babylonian law code of ancient Mesopotamia) Primum non nocere DO NO HARM

5 Bio-Medical Ethics? Clinical Ethics Service related provider / patient relationship (social) Targets service providers Code of Conduct Research Ethics Research with special reference to commercialized research vested interest of sponsor / investigator Targets supervision / monitoring of conduct of research

6 Questions? Comments!!!

7 Why Ethics? History

8 Landmark Article on US Abuses Henry Beecher NEJM, 1966

9 Why Ethics? History

10 Ethical Principles and Guidelines for the Protection of Human Subjects of Research National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research April 18, 1979

11 Why Ethics? History

12 Questions? Comments!!!

13 Relationship Definitions Ref: Oxford English Dictionary 2001 Principles A general truth that is used as a basis for a theory or system of belief for governing one s personal behaviour Guidelines A piece of advice or an indication as to how something should be done Regulations Law: A rule/system of rules made by an authority, recognized by a country / community as governing actions of its members that controls correct behaviour Rule: A statement of code of practice and discipline that must be done or not done for control of a group, community, or country

14 Bioethics What are the basic principles? Beneficence & Non-maleficence Do GOOD and Do NO HARM Double Effect or Combined Effect Autonomy Respect for persons Conflicts between Autonomy & Beneficence Justice Fairness, equal distribution of risks & benefits Ultimate AIM: Human participant protection

15 Principles little elaborate Beneficence and Non-malficence Identification of Risks minor / major Risk Minimization Benefits direct / indirect / no benefit / society Appropriate Risk vs Benefit ratio Respect for individuals Informed Consent / Protection of Vulnerable people Privacy and Confidentiality Justice Equitable selection / Equal distribution of burdens and benefits Post trial benefits / prior agreements

16 Public Health Ethics: Principles General principles: Beneficence, Non-maleficence, Respect for individuals (Personalistic principle), & Justice Harm principle: exercising power over an individual (against will), to prevent harm to others (John Stuart Mill) Principle of Least Restrictive / Coercive Means: more coercive methods employed only on failure of less coercive means, provided legal & necessary (Siracusa principle)

17 Public Health Ethics: Principles Reciprocity principle: society must facilitate PH in their efforts to discharge their duties (Harris & Holm) Transparency principle: Decision making must involve all legitimate stakeholders & must be clear and accountable Ref: Upshur Principles for the justification of public health intervention Canadian Journal of Public Health 2002; 93 (2):

18 Bioethics Guidelines Ethical Guidelines for Biomedical Research on Human Participants (Feb 1980, rev Sept 2000, rev 2006, ) Good Clinical Practices: Guidelines for Clinical Trials on Pharmaceutical products in India, 2001 National Guidelines for Accreditation, Supervision & Regulation of ART Clinics in India, 2005 Ethical Guidelines for Bio-banking in India, 2006 Guidelines for Stem Cell Research & Therapy, 2007

19 India - Guidelines Guidelines for Stem Cell Research And Therapy Department of Biotechnology and Indian Council of Medical Research Department of Health Research 2007

20 Questions? Comments!!!

21 Bioethics Laws and Rules Drugs and Cosmetics Act (DCA) 1940 & Rules , Schedule Y 1988, amendments 2005, 2011, 2013 Code of Medical Ethics Regulations Professional Conduct, Etiquette, & Ethics for RMPs 1956, rev 2002, amended 2003, 2004, 2009 Duties of Physicians 8 chapters General, towards patients, consulting process, peers, public Unethical acts, misconduct, punishment/disciplinary action Prevention of Cruelty to Animals Act (PCA Act) 1960 (59 of 1960) (Animal Welfare Board of India) Breeding of and Experiments on Animals Rules, 1998 (Ministry of Environment and Forests) Amendment Rules, 2001 & 2006

22 Regulations: evolution (Manufacture and Sale of drugs in India) Beginning 20 th century - no drug industry in INDIA drugs imported for use During I World War Pharmaceuticals manufacturing drugs Glamour for swadeshi goods No specific laws or rules to govern import of drugs or to ensure uniform quality of manufactured drugs Reports of poor quality drugs being freely available Government felt the need for comprehensive legislation Drugs enquiry committee in Chopra Committee Committee s report, GOI passed the Drugs Act in 1940 to regulate import, manufacture, distribution, and sale of drugs

23 Drugs and Cosmetics Act Divided in Chapters, Rules, and Schedules to cover all aspects related to drug regulation Regulation of manufacture, sale and distribution of drugs - State authorities Approval of New Drugs, Clinical Trials, laying down standards for Drugs, control over the quality of imported Drugs Central authorities CDSCO Central Drugs Standard Control Organization through DCGI regulatory body

24 Schedule Y 1988, CDSCO added Schedule Y to the DCA 1940 Mandatory for pharmaceutical companies to demonstrate safety and efficacy of a new drug before obtaining a license DCA 1940 (23 of 1040), Schedule Y (1988) Rules 122A, 122B, 122D, 122DA, 122DAA and 122E: Requirements and guidelines for Permission to Import and/or Manufacture of New drugs for sale or Undertake Clinical Trials Schedule Y Amendment 2005 (20 th January 2005) DCA Amendment 2013 (29 th August 2013)

25 Further Evolution!!! India joined World Trade Organization (WTO) 1995: Signatories have to protect product patents Full compliance with product patent regimen in 2005 Amendment of the DCA 1940 in 2005 Permitted Industry to (i) repeat Phase I trials in India (ii) commence Phase II trials in conjunction with same trials at other sites India: an attractive destination for clinical research

26 Clinical trial: concerns The protection of the rights, safety, and wellbeing of the research participants Interesting disease profile in India High burden of infectious communicable and non communicable diseases Rising prevalence of chronic life-style diseases Presence of a vast treatment-naïve population Adequate manpower and infrastructure at lower cost Ensuring the quality & integrity and accuracy & validity of the data obtained from clinical research

27 Circular by Deputy Director, Tribal Welfare Department authorizing Warden / Head of school to give consent for residents Parents gave consent for non-residents but were ignorant of consequences Captive vulnerable participants - Tribal minor girls in Hostel Misconception public immunization program, vaccine free of cost No institutional ethics committee review

28 Amendment Rules Drugs and cosmetics (first amendment) rules, 2013 Gazette notification G.S.R. 53(E), 30 Jan 2013 & (sixth amendment) rules, 2014 Gazette notification GSR 889 (E), 12 Dec 2014 Rule 122DAB: Compensation in case of injury / death during clinical trial Drugs and cosmetics (second amendment) rules, 2013 Gazette notification G.S.R. 63(E), 1 Feb 2013 Rule 122DAC: Permission to conduct clinical trial (SAE reporting) Drugs and cosmetics (third amendment) rules, 2013 Gazette notification G.S.R. 72(E), 8 Feb 2013 Rule 122DD: Registration of Ethics Committees Drugs and cosmetics (second amendment) rules, 2013 Gazette notification G.S.R. 364(E), 7 June 2013 Draft Rules: Audio-video recording of informed consent process DCGI Order dated 19 Nov 2013 (in addition to obtaining written IC)

29 What needs to be done?

30 Questions? Comments!!!

31 Thank You