Dr.T.V.Rao MD 1

MEDICAL ETHICS INRESEARCH PROPOSALS

( Indian contest ) Adopted by

Dr.T.V.Rao MD

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Dr.T.V.Rao MD 2

Why Program on Medical ethics

• I wish to state this not a complete program on Medical ethics, however it is made with many observations of the researchers and postgraduate students who present the Thesis, research proposals for PhD and application for ICMR

projects, I wish this program can be searched faster to make a basic idea when choosing the topic presenting the work before the ethical committee,

• Dr.T.V.Rao MD• Email doctortvrao@gmail.com

• Mob 9961785124

•

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Dr.T.V.Rao MD 3

Ethical guidelines •The “Ethical guidelines for biomedical research on human participants” prepared by the Indian Council of Medical Research in 2006 came as a welcome step in the process of regulation of search on human subjects, since clear cut Indian guidelines were absent earlier

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Dr.T.V.Rao MD 4

Research Ethics and Integrity• Research, in all domains, is an

important activity of every human society and represents a major commitment on the part of the various people involved, whether in the public or private sector. Research results constitute the basis for political and technical decisions, it is essential that the research itself be conducted with integrity, in a responsible manner and in accordance with high ethical standards.

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Dr.T.V.Rao MD 5

History of Ethical Codes in Human Research

• The first International Statement on the ethics of medical research using human subjects namely, the Nuremberg Code was formulated in 1947. Although informed consent for participation in research was recorded in 1900, the Nuremberg Code highlighted the essentiality of voluntariness of this consent.

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Dr.T.V.Rao MD 6

Ethics incorporate Human rights

•Declaration of Human Rights (adopted by the General Assembly of the United Nations) expressed concern about rights of human beings being subjected to involuntary maltreatment19-06-2016

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Rights of Humans Redefined• In 1966, the International

Covenant on Civil and Political• As states - • Rights specifically stated,

‘No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment. In particular, no one shall be subjected without his consent to medical or scientific treatment.’

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Helsinki Declaration• Based on the preliminary efforts

of the Council for International Organisations of Medical Sciences (CIOMS) in 1964 at Helsinki, the World Medical Association formulated general principles and specific guidelines on use of human subjects in medical research, known as the Helsinki Declaration, which was revised from time to time.

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Dr.T.V.Rao MD 9

NEW EDITION OF THE DECLARATION OF HELSINKI

• In June 1964, the World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.

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Proposed guidelines by WHO• In 1982,the World Health Organisation (WHO) and the CIOMS issued the ‘Proposed International Guidelines for Biomedical Research involving Human Subjects.’ B -Subsequently the CIOMS brought out the ‘International Guidelines for Ethical Review in Epidemiological studies’ in 1991 and ‘International Ethical Guidelines for Biomedical Research involving Human Subjects19-06-2016

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ICMR FORMULATES ITS OWN GUIDLIENS

• In February 1980, the Indian Council of Medical Research released a ‘Policy Statement on Ethical Considerations involved in Research on Human• Subjects’ for the benefit of

all those involved in clinical research in India.

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Most recent guidelines on Human Research

The most recent documents on ethics are• Those of UNESCO’s “The Universal

Declaration on Human Genome and Human Rights” (1997), “The International Declaration on Human Gene Data” (2003)and “Universal Declaration on Bioethics and Human Rights” (2005).

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ICMR GUIDELINES BECOMES SOP’S

• "Ethical guidelines for biomedical research on human participants" prepared by the Indian Council of Medical Research in 2006 came as a welcome step in the process of regulation of research on human subjects, since clear cut Indian guidelines were absent earlier

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ICMR guidelines accepted as SOP’s

• The guidelines have been accepted as the standard operating manual by Institutional Ethics Committees (IEC) in India

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Purpose of Research to be Defined

• The PURPOSE, of such research is that it should be directed towards the increase of knowledge about the human condition in relation to its social and natural environment, mindful that the human species is one of the many species in a planet in which the well being of all species is under threat, no less from the human species as any other, and and that such research is for the betterment of all, especially the least advantaged.

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GENERAL ETHICAL PRINCIPLES•General ethical principles of respect for persons, duty to maximize possible benefits and minimise possible harm are important considerations in ethical guidelines. At the same time it is essential that all individuals in an epidemiological research are treated alike keeping in mind the rules of distributive justice19-06-2016

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GENERAL PRINCIPLES•The welfare of the individual has to be balanced against the welfare of the community and society at large. The C.I.O.M.S / W.H.O Guidelines for Epidemiological Research assume that the individuals or populations being studied are capable of giving informed consent understanding the implications of the study.

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CONDUCTED under conditions• Such research is CONDUCTED under conditions that no

person or persons become a mere means for the betterment of others and that human beings who are subject to any medical research or scientific experimentation are dealt with in a manner conducive to and consistent with their dignity and well being, under conditions of professional fair treatment and transparency; and after ensuring that the participant is placed at no greater risk other than such risk commensurate with the well being of the participant in question in the light of the object to the achieved.19-06-2016

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Regime of EVALUATION • Such research must be subjected to a regime of

EVALUATION at all stages of the proposal i.e., research design and experimentation, declaration of results and use of the results thereof, and that each such evaluation shall bear in mind the objects to be achieved, the means by which they are sought to be achieved, the anticipated benefits and dangers, the potential uses and abuses of the experiment and its results, and above all, the premium that civilised society places on saving and ensuring the safety of each human life as an end in itself.

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Dr.T.V.Rao MD 20

STATEMENT OF GENERAL PRINCIPLES IN BIOMEDICALRESEARCH INVOLVING HUMAN PARTICIPANTS

• Statement of Ethical Guidelines for Biomedical Research on Human Participants shall be known as the ICMR Code and shall consist of the following:- (a) Statement of General Principles on Research using Human Participants in Biomedical Research• (b) Statement of Specific Principles on Research

using Human Participants in specific areas of Biomedical Research

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BASIC RESPONSIBILITIES of Ethical Committee

• The basic responsibility of an Institutional Ethics Committee (IEC) is to ensure a competent review of all ethical aspects of the project proposals received by it in an objective manner. IECs should provide advice to the researchers on all aspects of the welfare and safety of the research participants after ensuring the scientific soundness of the proposed research through appropriate Scientific Review Committee

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Always assess the Technical Appropriateness

•The scientific evaluation should ensure technical appropriateness of the proposed study. The IECs should specify in writing the authority under which the Committee is established.

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COMPOSITION of Ethical Committee

• The IECs should be multidisciplinary and multi sectorial in composition. Independence and competence are the two hallmarks of an IEC. The number of persons in an ethics committee should be kept fairly small (8 - 12 members).

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All decisions are subject to Quorum

• It is generally accepted that a minimum of five persons is required to form the quorum without which a decision regarding the research should not be taken. The IEC should appoint from among its members a Chairman who should be from outside the Institution and not head of the same

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Eligible to be a Chairman The IEC should appoint from among its members a Chairman who should be from outside the Institution and not head of the same members or Institute not head of the same Institution to maintain the independence of the Committee.

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Ethical Committee is composed of mixed group of

people •Other members should be a mix of medical/ non-medical, scientific and non-scientific persons including lay persons to represent the differed points of view.• :19-06-2016

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The composition may be as follows

• 1. Chairperson• 2. One - two persons from basic medical science area• 3. One - two clinicians from various Institutes• 4. One legal expert or retired judge• 5. One social scientist/ representative of non-governmental

voluntary agency• 6. One philosopher/ ethicist/ theologian• 7. One lay person from the community• 8. Member Secretary19-06-2016

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As per revised Schedule Y of Drugs & Cosmetics Act, 1940, amended in 2005,

• As per revised Schedule Y of Drugs & Cosmetics Act, 1940, amended in 2005, the ethics committee approving drug trials should have in the quorum at least one• representative from the following groups:• 1. One basic medical scientist (preferably one pharmacologist).• 2. One clinician• 3. One legal expert or retired judge• 4. One social scientist/ representative of non-governmental organisation/• philosopher/ ethicist/ theologian or a similar person• 5. One lay person from the community.

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The Members can from other Institutes too

• The Ethics Committee (EC) can have as its members, individuals from other institutions or communities with adequate representation of age and gender to safeguard the interests and welfare of all sections of the community/society. If required, subject experts could be invited to offer their views, for instance, a paediatrician for paediatric conditions, a cardiologist for cardiac disorders etc. Similarly, based on the requirement of research area, for example HIV, genetic disorders etc. it is desirable to include a member from specific patient groups in the Committee.19-06-2016

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Training Ethical Committee Members

• The EC members should be encouraged to keep abreast of all national and international developments in ethics through orientation courses on related topics by its own members or regular training organized by constituted body(ies), so that they become aware of their role and responsibilities19-06-2016

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Members to be trained on Good Clinical Practice

• For drug trial review it is preferable to train the IEC members in Good Clinical Practice. Any change in the regulatory requirements should be brought to their attention and they should be aware of local, social and cultural norms, as this is the most important social control mechanism. .19-06-2016

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SUBMISSION OF APPLICATION• The researcher should submit an application in a prescribed

format along with the study protocol as prescribed in SOP of IEC concerned. The protocol should include the following : -• 1. The title with signature of Principal Investigator (PI) and

Co-• investigators as attestation for conducting the study.• 2. Clear research objectives and rationale for undertaking the

investigation in human participants in the light of existing knowledge

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SUBMISSION OF APPLICATION• 3. Recent curriculum vitae of the Investigators indicating qualification

and experience.• 4. Participant recruitment procedures and brochures, if any.• 5. Inclusion and exclusion criteria for entry of participants.• 6. Precise description of methodology of the proposed research,

including sample size (with justification), type of study design (observational, experimental, pilot, randomized, blinded etc.), intended intervention, dosages of drugs, route of administration, duration of treatment anddetails of invasive procedures if any.

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SUBMISSION OF APPLICATION• 7.Plan to withdraw or withhold standard therapies in the course of

research.• 8.Plan for statistical analysis of the study.• 9.Procedure for seeking and obtaining informed consent with sample

of patient information sheet and informed consent forms in English and local languages.• 10. Safety of proposed intervention and any drug or vaccine to be

tested, including results of relevant laboratory, animal and human research.

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SUBMISSION OF APPLICATION• 11. For research involving more than minimal risk, an

account of•management of such risk or injury.• 12. Proposed compensation and reimbursement of incidental

expenses and management of research related and unrelated injury/ illness during and after research period.• 13. An account of storage and maintenance of all data

collected during the trial

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SUBMISSION OF APPLICATION• 14. Plans for publication of results - positive or negative - while

maintaining• the privacy and confidentiality of the study participants.• 15. A statement on probable ethical issues and steps taken to tackle the• same like justification for washout of standard drug, or the use of placebo• control..• 16. All other relevant documents related to the study protocol

like investigator's brochure for trial on drugs/ devices/ vaccines/ herbal remedies and statement of relevant regulatory clearances.

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SUBMISSION OF APPLICATION• 17.Agreement to comply with national and international Good Clinical

Practices (GCP) protocols for clinical trials.• 18. Details of Funding agency/ Sponsors and fund allocation.• 19. For international collaborative study details about foreign

collaborators and documents for review of Health Ministry's Screening Committee(HMSC) or appropriate Committees under other agencies/authority like Drug Controller General of India (DCGI)• 20. For exchange of biological material in international collaborative study

aMoU/ Material Transfer Agreement between the collaborating partners.• 21.A statement on conflict-of-interest (COI), if any.

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Standard Operating Procedures for Ethics

Committee • The guidelines have been accepted as the standard operating manual by Institutional Ethics Committees (IEC) in India.

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All participants to be educated and oriented on Ethics

before Starting the Research Work

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Need for Educating many participants and ethical

committee Member • At present, ethical issues in research in India do not get the attention they deserve, particularly outside major full-time research organisations. Utmost clarity is required to avoid difficulties in interpretation, or shades of opinion not intended by the ICMR.

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Trials on as yet non-approved drug

• The guidelines state “The proposed trial should be carried out, only after approval of the Drugs Controller General of India (DCGI), as is necessary under the Schedule Y of Drugs and Cosmetics• Act, 1940. The investigator should

also get the approval of Ethical Committee of the Institution before submitting the proposal to DCGI.”

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Have knowledge on Trails going on in the

Community

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Access to benefits of therapy

IT IS THE PART OF THE ETHICS • The Helsinki Declaration of the World

Medical Assembly, 2008(2), states that “at the conclusion of the study, patients entered in to the study are entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits.”

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The ICMR guidelines• “After the clinical trial is over, if

indeed the drug is found effective, it should be made mandatory that the sponsoring agency should provide the drug to the patient till it is marketed in the country and thereafter at a reduced rate for the participants whenever possible. A suitable a priori agreement should be reached on post-trial benefits

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Informed Consent means • Informed consent is a process for

getting permission before conducting a healthcare intervention on a person. A health care provider may ask a patient to consent to receive therapy before providing it, or a clinical researcher may ask a research participant before enrolling that person into a clinical trial. Informed consent is collected according to guidelines from the fields of medical ethics and research ethics.

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All the Informed Consents to be Free, Frank and

Understandable to be Patients

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Getting Informed consent can be challenging

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Consent and assent for epidemiological studies onminors and school children

• ICMR guidelines also say: "the assent of the child should be obtained to the extent of the child’s capabilities such as in the case of mature minors from the age of seven years up to the age of 18 years.”

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Right of Participants to withdraw from the Research

assessments • The right of participants in

research to decline to participate, or withdraw, or abstain from further participation, has been repeatedly emphasised by the ICMR guidelines. It has been clearly stated that the patients can “withdraw without penalty or loss of benefits which the participant would otherwise be entitled to.”

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In-house monitoring and ongoing review process

• The greatest problem with the working of the IEC in any institute is the lack of an ongoing monitoring process to ensure that the guidelines have been followed, that there is no deviation from the protocol, and that any adverse effects are reported. In actual practice,

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Cohort Studies• These are longitudinal or prospective studies of a group of

individuals with differing exposure levels to suspected risk factors. They are observed over a long period usually several years. The rate of occurrence of the condition of interest is measured and compared in relation to identified risk factors.• It requires a study of large number of participants for a long time

and involves asking questions, checking of records, routine medical examination and sometimes laboratory investigations. Individuals are being followed up as the cohort and it is essential to identify precisely every individual to be studied.

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Follow the Principals of Cohort Studies

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Research on archived ( retrospective} specimens

• The guidelines permit an expedited review on “research involving clinical materials (data, documents, records or specimens) that have been collected for non-research (clinical) purposes.” No further instructions are provided as to how this information is to be dealt

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Waiver of consentICMR guidelines mentions that “voluntary informed consent … “can be waived if it is justified that the research involves not more than minimal risk or when the participant and the researcher do not come into contact or when it is necessitated in emergency situations.”19-06-2016

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Consent Forms to be Simple and Understandable in local language and familiar to the participants

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Trial on non-allopathic drugs and herbal remedies

• These have become more numerous in recent times, particularly in medical colleges. The guidelines are quite clear on this issue: “when clinical trials of herbal drugs used in recognised Indian Systems of Medicine and Homeopathy are to be undertaken in Allopathic hospitals, association of physicians from the concerned system as co-investigators/collaborators / members of the expert group is desirable

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Ethics of live operative workshops

•Operative workshops call for a situation where a visiting surgeon performs a procedure, which may be major, on a patient whom s/he has not seen before, or perhaps not interacted with in any detail or any length of time before. It also involves circumstances where's/he has no responsibility for preoperative or postoperative care; this is left to the parent institution conducting the workshop. 19-06-2016

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Support, guidance and reportingWe the Committee members have responsibility • Providing information, support and guidance to staff and students;• Administrative support for the Animal Research and Human Research

Ethics Committees;• liaising between Committees and applicants;• preliminary reviews of applications and provision of feedback to

applicants;• monitoring approved research projects;• developing, implementing, reviewing and updating policies and

procedures; and• reporting to the University, the National Health and Medical Research

Council, and other organisations.19-06-2016

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Look at the Matters with Human perception and just for pure Research

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I am thankful to ……..• Iam thankful to The Principal, Vice

principal, Medical Director, the great efforts of Dr Sudha and Dr Vivek and all the members of the Ethical committee of Azezia Medical College Kollam Kerala for making my job easier, and inspires me to do work ethically

Dr.T.V.Rao MD Chairman Intuitional Ethical Committee Azezia Medical College Kollam Kerala

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References • Ref 1 ETHICAL GUIDELINES FOR BIOMEDICAL RESEARCHON HUMAN

PARTICIPANTS, NDIAN COUNCIL OF MEDICAL RESEARCH NEW DELHI2006 ; M. S. Valiathan Chairman Central Ethics Committee on Human Research ICMR, New Delhi• 2 ICMR’s Ethical guidelines for biomedical research on human participants: need

for clarification N Ananthakrishnan, Shanthi AK ETHICS OF ETHICS COMMITTE. Indian Journal of Medical Ethics Vol IX No 3 July - September 2012

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•Program Created by Dr.T.V.Rao MD on Basics to understand the Human Ethics

to Initiate the Medical research •Email

•doctortvrao@gmail.com

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