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.