Ethical issues in Research
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
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
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”
Human Rights & Health
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.”
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………….
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
RIGHTS AND RESPONSIBILITIES OF INSTITUTIONS
Respect autonomy of researchers
Support ethical guidelines
Should have Institutional Ethical committee
Observance of ethical guidelines for research
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
COMPOSITION OF IEC
7-9 members
1. Chairperson2. 1-2 basic medical scientists.3. 1-2 clinicians from various Institutes4. One legal expert or retired judge5. One social scientist / representative of NGO6. One philosopher / ethicist / theologian7. One lay person from the community8. Member-Secretary Subject expert/ Independent consultants
Duration of Membership – 2-3 years
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
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
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
RIGHTS OF PARTICIPANTS INFORMED CONSENT
1. Patient information sheet---Nature and purpose of study2. Duration of participation with number of participants3. Procedures to be followed4. Investigations, if any5. Foreseeable risks and discomforts 6. Benefits to participant/ community /medical profession 7. Policy on compensation8. Medical treatment for injuries or risk 9. Alternative treatments if available10. Steps taken for confidentiality11. No loss of benefits on withdrawal12. Benefit sharing in event of commercialization13. Contact details of PI or local PI/Co-PI in Multicentric14. Contact details of Chairman of IEC for appeal against violation of rights15. Voluntary participation16. If test for genetics & HIV, counseling for consent for testing must be
given as per national guidelines17. Storage period of biological sample and related data 18. Copy to participant
Written consent not possible? Third person, audio-visual but needs approval of IEC
Age?
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
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
Epidemiological studies
Drug trials
Vaccine trial
Herbal extracts/ Unani/ Siddha
Medical device/diagnostic devices
Tissue/organ transplants
Ethical issues in various research setting
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.
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
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
DRUG TRIAL………….
Phase IChange 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 IIThe 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
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
VACCINE TRIALS
Contain active or live – attenuated
Standard vaccine -if no – community involvement
Control groups- Post trial access
Certification of vaccination
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.
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
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
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
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
INTERACTING WITH MEDIA
Avoid dissemination till published
No false hopes or expectations or unnecessarily scare raise
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
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
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
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.
CHALLENGES
Use of placebo or standard?
Paying researcher: Motivation Or Inducement?
Training of IEC members
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. 2nd ed . New Delhi: Jaypee brothers, 2004.
Ravindran GD. Medical ethics education in India. Indian journal of medical ethics 2008 Jan-Mar;5(1):18-26.