Ethical issues in Research

1. Ethical issues in Research

2. Framework • History • Human Rights & health • Ethics in medical practice & research • Declaration of Helsinki, 2008 • Rights and Responsibilities of Researcher • Rights and Responsibilities of Institutions • Institutional Ethics Committee (IEC) • Relationship among researchers • Selection of research participants • Informed Consent • Rights of participants • Ethical issues in various research setting • Epidemiological studies • Drug trials • Vaccine trial • Research involving medical device/ diagnostic devices • Herbal extracts/ Unani/Siddha • Tissue/Organ Transplants • Issue related to reporting/ publishing • Rights & responsibility of funders/ sponsors

3. Introduction • Ethics is study of morality – careful & systematic reflection on & analysis of moral decisions & behavior, whether past, present or future. • Medical ethics • To recognize difficult situations & to deal with them rational & principled manner. • to safe guard humanity

4. History • 1947 - Nuremberg Code • 1947 - World Medical Association established • 1948 -Universal Declaration of Human Rights (General Assembly UN) • 1954 –Principles for Research and Experimentation (WMA) • 1966 -International Covenant on Civil and Political Rights • 1964 - Declaration of Helsinki (1975, 1983, 1989, 1996, 2000, 2008) • 1980 - Policy Statement on Ethical Considerations involved in Research on Human Subjects ( ICMR) • 1982 - International Guidelines for Biomedical Research involving Human Subjects (WHO & CIOMS ) • 1991 - International Guidelines for Ethical Review in Epidemiological studies (CIOMS) • 1993 - International Ethical Guidelines for Biomedical Research Involving Human Subjects (revised 2002) (CIOMS) • 2000 - 'Ethical guidelines for Biomedical Research on Human Subjects (ICMR) • 2003 - The International Declaration on Human Gene Data (UNESCO) • 2005 -Universal Declaration on Bioethics and Human Rights (UNESCO) • In 2006, ICMR published “Ethical guidelines for biomedical research on human participants”

5. Human Rights & Health

6. Ethics in medical practice & research Basic principles • Non-maleficence • Beneficence • Autonomy • Justice • Declaration of Geneva - “The health of my patient will be my first consideration” • International Code of Medical Ethics - “A physician shall act in the patient's best interest when providing medical care.”

7. Declaration of Helsinki, 2008 • 3)6) …duty to safe guard participants….well being of research subject….. • 7)21)…..primary purpose…improve present knowledge…..outweighs risk • 10) …consider.. National & international norms……. • 14) ….Protocol…..ethical issues….. • 16) …by scientifically trained & qualified…………… • 17)…..vulnerable & disadvantages…………fulfill their health needs….. • 19)…..trials must registered…..public database…………… • 22) …..participation …..voluntary…….. • 25)…..human material & data……consent for collection, analysis, storage, reuse …if not possible…..from research ethics committee…. • 28 ) ….incompetent research subject…….consent from legal authority…. • 30 )…Authors, publishers & publisher……results available publicly…… • 31) …….medical practice & research ….combined…if justified. • 32) …new intervention..against best current proven intervention …except in ….no treatment…..or compelling & sound methodological reason ..not subjected to any risk……… • 33) …if beneficial….then post intervention access………….

8. Rights and Responsibilities of Researchers • Qualification and competent • Research should improve of knowledge on the subject • No secret research – bring to public domain • Should follow ethical guidelines • honesty and transparency • Respect, Protection & Promotion of rights of participants • Unethical study, then can quit • Right to publication • Peer review

9. Rights and Responsibilities of Institutions • Respect autonomy of researchers • Support ethical guidelines • Should have Institutional Ethical committee • Observance of ethical guidelines for research

10. Institutional Ethics Committee (IEC) Functions • To resolve ethical dilemmas • To safeguard dignity, rights, safety & well being of actual & potential participants • Taking care of principle of ethics • To support the researcher in ethical issues • To examine compliance with all regulatory requirements, applicable guidelines and laws • Ethical clearance irrespective of funding agency

11. Composition of IEC 7-9 members • Chairperson • 1-2 basic medical scientists. • 1-2 clinicians from various Institutes • One legal expert or retired judge • One social scientist / representative of NGO • One philosopher / ethicist / theologian • One lay person from the community • Member-Secretary Subject expert/ Independent consultants • Duration of Membership – 2-3 years

12. Application Procedures & Documents • Prescribed application form • Name of applicant with designation • Name of Institute/ Hospital / Field area where research will be conducted. • Approval of HOD/ Institution • Protocol of proposed research • Ethical issues in study & plans to address these issues. • Proposal should be submitted with all relevant enclosures like proformas, case report forms, questionnaires, follow - up cards, etc. • Informed consent process, including patient information sheet and informed consent form in local language(s). • For any drug / device trial, all relevant pre-clinical animal data and clinical trial data from other centres within country / countries, if available. • Curriculum vitae of all the investigators with relevant publications in last five years. • Any regulatory clearances required. • Source of funding and financial requirements for the project. • Other financial issues including those related to insurance • An agreement to report only Serious Adverse Events (SAE) to IEC. • Statement of conflicts of interest, if any. • Agreement to comply with the relevant national and applicable international guidelines. • A statement describing any compensation for study participation (including expenses and

13. Review procedures: • Proposals sent to members at least 2 wks in advance • Meetings on scheduled intervals • Minimum 5 member for decision • Decision by meeting not by circulation • Researchers will be invited to offer clarifications if need • Minute & notification by member secretary • Communicating decision • Record keeping & Archiving • Updating IEC members

14. Selection of as research participants • be completely voluntary • should give informed written consent • no inducement but compensation( risk benefits, out of pocket expenses) • No unjustifiable assurance • Anonymity & confidentiality • Selection of special groups as research participants • Pregnant or nursing women • Children - after phase III • Vulnerable groups

15. Rights of participants Informed Consent 1. Patient information sheet---Nature and purpose of study 2. Duration of participation with number of participants 3. Procedures to be followed 4. Investigations, if any 5. Foreseeable risks and discomforts 6. Benefits to participant/ community /medical profession 7. Policy on compensation 8. Medical treatment for injuries or risk 9. Alternative treatments if available 10. Steps taken for confidentiality 11. No loss of benefits on withdrawal 12. Benefit sharing in event of commercialization 13. Contact details of PI or local PI/Co-PI in Multicentric 14. Contact details of Chairman of IEC for appeal against violation of rights 15. Voluntary participation 16. If test for genetics & HIV, counseling for consent for testing must be given as per national guidelines 17. Storage period of biological sample and related data 18. Copy to participant

16. Written consent not possible? Third person, audio-visual but needs approval of IEC • Age?

17. Fresh or re-consent • Deviation of protocol • Regains consciousness from unconscious • Change in treatment modality, procedures, site, visits • Before publication Waiver of consent • Not more than minimal risk • Do not come into contact • When it is necessitated in emergency situations • Research on anonymised biological samples from deceased individuals

18. Relationship among researchers Principal researchers are responsible • Ethical conduct but juniors, assistants, students & trainees have an equally responsibility • Training to junior, assistants • No discrimination • Researchers should not mislead or force other researchers • Co-operative, responsive, honest and respectful about the interest, opinion/view, capability and work of other researchers

19. Ethical issues in various research setting • Epidemiological studies • Drug trials • Vaccine trial • Herbal extracts/ Unani/ Siddha • Medical device/diagnostic devices • Tissue/organ transplants

20. Ethical issues in epidemiological studies • Consent from community &Community participation • Inducements are not permissible • All risks involved – explained to individual & community • Maintaining confidentiality • Minimize harm, maximum benefit for individuals and communities taking part in study • Committees -- epidemiologists, clinicians, statisticians, social scientists, philosophers, legal experts and representatives from community/ voluntary groups • Should not raise false hopes.

21. Ethical principles for drug trial • Drugs Controller General of India (DCGI), (Drugs and Cosmetics Act, 1940) • Approval of IEC • All guiding principles -irrespective of place of discovery of drug • Risk-benefit should be favorable. • It should registered as per International standard RCT • Should be carried out in equipped center, m/m ASE • Preferably clinical pharmacologist involved. • Use of a placebo in drug trials/ sham surgery i. self limited disease; ii. where no proven prophylactic, diagnostic or therapeutic method exists

22. Drug trial ……. • Post trial benefit • Criteria of termination • Breaking of code • Partner notification -HIV/ AIDS related trial New drug (India)- Phase I to IV New drug (outside India)- Phase I data required

23. Drug trial…………. Phase I Change in protocol -approval of IEC must Started from lowest dose Sub-populations Duration between 2 trials in same volunteer - 3 mths Compensation is given by the sponsors or insurance Phase II The dose used is lesser than the highest dose used in phase I Phase III • Drug in Indian patients • Open non-comparative trials are unethical. Phase IV • doesn’t require approval from DCGI

24. Multicentric Trials • Acceptance of the protocol • Approval IECs • Meetings at initial & intermediary stages – Central monitoring committee • Training – uniformity procedures, data entry in the case record forms, ethics & GCP Trial involving contraceptive • Information about alternatives available • Implant- proper follow & removal • Failure of contraceptives Monitoring and reporting adverse reactions or events • unexpected AE/ADR & all SAE (Indian Good Clinical Practice(GCP) Guidelines) Investigator to sponsers -24 hrs Investigator to EC - < 7 days Death information to Ec – 24 hrs Sponsor to Licensing Authority &Investigator(s) of other site -14 calendar days • Evaluated and discussed • Medical management of adverse event • financial plan for trial related injury

25. Vaccine trials • Contain active or live – attenuated • Standard vaccine -if no – community involvement • Control groups- Post trial access • Certification of vaccination

26. Clinical trials with surgical procedures / medical devices • Safe procedures • Indian Medical Devices Regulatory Authority (IMDRA)- Health Ministry • Indian Standard Institute, Board of Indian Standards, Drug Controller General of India, and Nuclear Medicine Board of the BARC • Informed consent as in drug trials • Patient information sheet- information on follow-up if withdraw from trial.

27. Diagnostic agents - use of radio- active materials and X-rays • Participants & investigators are exposed • Bhabha Atomic Research Centre, Mumbai • Informed consent must- possible genetic damage to offspring & other risk • Safety measures • Event of death of a participant with radiological implant • Done on patients undergoing diagnostic or therapeutic purposes. • Substitute Ultrasound • Non-radioactive diagnostic agents considered as drugs

28. Clinical evaluation of traditional ayurveda, siddha, unani(asu) remedies & medicinal plants “Operational Guidance: Information needed to support clinical trials of herbal products (2005)” ---WHO • Drugs Controller General of India • Categories of drugs • Cat I – No Phase I • Cat II & III – Phase I -IV

29. Ethical issue organ transplantation research • Institutional Committee for Stem Cell Research and Therapy (IC-SCRT) & National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) • Centers registration with NAC-SCRT & Equipped institutions • No deliberate conception and /or subsequent abortion • No research is permitted on the live aborted foetus. • Voluntary, informed, written consent from mother 2 stages – 1st for the abortion 2nd for donation of tissue from the foetus. • Termination of pregnancy for financial or therapeutic benefits • Intact embryos or foetuses will not be kept alive artificially • Cells obtained from fetuses will not be patented for commercial

30. Reporting of results of research • support ?or contradict ? • Cource(s) of funding and sponsors • Report explain methodology, how ethical guidelines followed, ethical dilemmas encountered and resolved, etc. • No any keep secrete results. • Who will? Investigators? Institution? Sponser? • Ensure easy availability & accessibility • Conflict of interest

31. Interacting with media • Avoid dissemination till published • No false hopes or expectations or unnecessarily scare raise

32. Rights and Responsibilities of Peer Reviewers/Referees • Encouraged to improve and advance research • Peer reviewer in expertise field • Undertaking objectively, impartially and constructively • Actual or potential conflicts of personal or professional interest • Malpractices in research or violation of ethics

33. Publication in scientific journal • Clear consent for publication from participants • Confidentiality • Authorship - International Committee of Medical Journal Editors (ICJME) • Consolidated standards of reporting trials (CONSORT) guidelines

34. Rights & Responsibilities of Editors & Publishers • Ensure that such material is, duly reviewed by referees • As journalists & as researcher • Fabricated, falsified or plagiarized information - not be entertained • After publication - doubt is raised about its ethical status or ethical conduct of the study • Misconduct

35. Rights and Responsibilities of Funders and Sponsors • Right to expect progress of work & final report • Right to get a copy of ethical guidelines for research • Respect ethical guidelines for research & should not expect researchers and institutions to undertake research or conduct it in any way contrary to ethical guidelines.

36. Challenges • Use of placebo or standard? • Paying researcher: Motivation Or Inducement? • Training of IEC members

37. References: • World medical association. Medical ethics manual. 2nd Ed. UK: The World Medical Association Inc; 2009. • World Medical Association. Declaration of Helsinki: 2008. Seoul: TheWorld Medical Association Inc; 2008. • ICMR. Ethical guidelines For Biomedical research On Human participants. New Delhi: ICMR; 2006. • WHO. Operational Guidelines for Ethics Committees That Review Biomedical Research. Geneva: World health organization; 2000. • Amnesty International. Ethical codes & declarations relevant to the health professions. 4th Ed. London: Amnesty international; 2000. • CM Francis. Medical Ethics. 2nded . New Delhi: Jaypee brothers, 2004. • Ravindran GD. Medical ethics education in India. Indian journal of medical ethics 2008 Jan-Mar;5(1):18-26.