Institutional ethics committee & informed consent

Drowning in Seawater, Hypothermia & High Altitude
Experiments at Dachau

Tuskegee Study
28 deaths
100 cases of disability
19 cases of congenital Syphilis

HISTORY 1000 BC : Charaka Samhita
to 1-2 AD
 1947 : Nuremberg Code
 1956 : Code of Medical Ethics, MCI
 1964 : Helsinki Declaration
 1979 : Belmont Report
 1980 : Policy Statement on Ethical Considerations
involved in research on Human Subject (ICMR)

 1982/1992 : Proposed International Guidelines
(WHO/CIOMS)
 1988 : Schedule Y
 1997 : Guidelines for Exchange of Human Biological
Material for Biomedical Research Purposes
 2000 : Revised ICMR Ethical guidelines
 2001 : Indian GCP Guidelines

INTRODUCTION
GENERAL STATEMENT
Medical and related research using human beings as research participants must
necessarily ensure
1. PURPOSE - should be directed towards increase of knowledge about the condition
and for betterment of all human beings.
2. CONDUCT - under conditions of professional fair treatment and transparency, in a
manner consistent with dignity and well being of human subjects.
3. EVALUATION - research must be subjected to evaluation at all stages of the study.

GENERAL PRINCIPLES
1. Principles of essentiality
2. Principles of voluntariness, informed consent and community agreement.
3. Principles of non-exploitation.
4. Principles of privacy and confidentiality.
5. Principles of precaution and risk minimisation.
6. Principles of professional competence.
7. Principles of accountability and transparency.
8. Principles of the maximisation of the public interest and of distributive justice.
9. Principles of institutional arrangements.
10. Principles of public domain.
11. Principles of totality of responsibility.
12. Principles of compliance.

 The need for evaluation of research proposals has been emphasized
under the principle of precaution & risk minimisation.
 It is mandatory that all proposals on biomedical research involving human
participants should be cleared by an appropriately constituted Institutional
Ethics Committee (IEC), also referred to as Institutional Review Board
(IRB), Ethics Review Board (ERB) and Research Ethics Board (REB) in
other countries, to safeguard the welfare and the rights of the participants.
 The Ethics Committees are entrusted not only with the initial review of the
proposed research protocols prior to initiation of the projects but also have
a continuing responsibility of regular monitoring of the approved
programmes to foresee the compliance of the ethics during the period of the
project.

INSTITUTIONAL ETHICS COMMITTEE
(IEC)
 Committee comprising of medical, non-medical, scientific and
non-scientific members whose responsibility is to ensure the
protection of the rights, safety and well-being of human
subjects involved in the trial and it shall be responsible for
reviewing & approving the protocol, the suitability of the
investigators, facilities, methods & adequacy of information to
be used for obtaining and documenting informed consent of
the study subjects and adequacy of confidentiality safeguards.

STRUCTURE OF IEC
 Composition:
 Multidisciplinary and multi sectorial in composition
 Number of persons- 8-12 (not less than 7)
 Specific members of IECs:
 Chair person should preferably be from outside the
Institution to maintain the independence of the
Committee.
 Member secretary, from same institution should conduct
the business of the Committee

MEMBERS OF IEC
 Chair person
 1-2 basic medical scientists
 1-2 clinicians from various institutes
 One legal expert or retired judge
 One social scientist/representative of NG voluntary
agency
 One philosopher/ethicist/theologian
 One lay person
 Member Secretary

 As per revised Schedule Y of Drugs & Cosmetics Act, 1940, quorum should
consist of:
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.
 (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. 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.

MEMBERSHIP REQUIREMENTS
 The members representing medical scientists & clinicians should have post
graduate qualifications.
 The duration of appointment is initially for a period of 2-3 years
 At the end of 2-3 years, as the case may be, the committee is reconstituted, and
50% of the members will be replaced by a defined procedure.
 A member can be replaced in the event of death or long-term nonavailability
 A member can tender resignation from the committee with proper reasons to do
so.
 All members should maintain absolute confidentiality of all discussions during the
meeting and sign a confidentiality form.
 Conflict of interest should be declared by members of the IEC

REGISTRATION OF ETHICS COMMITTEE
 According to rule 122DD of the recent amendments of Schedule Y – “No ethics
committee shall review and accord its approval to a clinical trial protocol
without prior registration with the licensing authority.”
 The registration unless it is suspended or cancelled shall be valid for a period of
three years from the date of issue.
 If the ethics committee fails to comply with any of the conditions of registration,
the licensing authority may, after giving an opportunity to show cause, by an
order in writing stating the reasons there for, suspend or cancel the registration
of the ethics committee.
 The EC whose registration has been cancelled may within 90 days, appeal to
central govt and central govt after giving an opportunity of being heard, confirm,
reverse or modify such order.

FUNCTIONS OF IEC
 To provide competent review of all ethical aspects of the research project
 Undertake review free from bias and influence
 Provide advice to the researchers on all aspects of welfare and safety of
research participants
 To protect dignity, rights and well-being of the potential research
participants.
 To report all SAE (serious adverse events) to licensing authority.
 To provide an opinion on the compensation to research participants, if
any, in case of injury or death during clinical trial

DEATH/ SAE REPORTED BY PI LICENSING AUTHORITY
within 24 hr SPONSOR, EC
DEATH
detail report by SPONSOR/ PI (10 DAYS)
EXPERT COMMITTEE Copy to Licensing authority, Head of institution
ETHICS COMMITTEE
detail report by ethics committee (21 days)
CHAIRMAN OF EXPERT COMMITTEE Copy to licensing authority
expert committee recommendations (30 days)
LICENSING AUTHORITY
(3 months)
decides quantum of compensation
to be paid & pass necessary orders

SAE other than death
detail report by sponsor/PI (10 days)
LICENSING AUTHORITY, EC
HEAD OF INSTITUTION
detail report by Ethics committee (21 days)
LICENSING AUTHORITY
(may constitute independent expert committee)
within 3 months
decides quantum of compensation
to be paid & pass necessary orders
 Sponsor shall pay the compensation as per the order of Licensing authority within
30 days of receipt of such order.

IECs should establish standard operating procedures which should include
 Functions and duties of the IEC
 Determining its composition, quorum requirements.
 Scheduling & conducting meetings
 Conducting initial & continuing review of trials
 Providing according to regulatory requirements, expedited review
and approval of minor changes in ongoing trials that have the
approval of IEC
 Specifying that no subject should be admitted to a trial before the
approval of IEC

 Specifying that no deviation from or changes of the protocol should
be initiated without prior written IEC approval.
 Specifying that the investigator should promptly report to IEC
- deviations from the protocol to eliminate the risk to subjects
- changes increasing the risks to subjects
- all ADRs
- new information that may affect the safety of the subjects or
conduct of
the trial
 Ensuring that the IEC notifies the investigator concerning
- trial related decision
- reason for its decision

SUBMISSION OF APPLICATION FOR RESEARCH TO
IEC
 The following documents must be submitted:
- Trial Protocol (in prescribed format)
- Patient Information Sheet and Informed Consent Form and its
translations
- Investigators brochure
- Principal Investigator’s current C.V.
- Insurance policy/ compensation for participation
- Investigators Agreement with the sponsor

REVIEW OF PROJECT
 Scientific evaluation should be completed before ethical evaluation
 Evaluate possible risks to the subjects with proper justification
 Expected benefits
 Adequacy of documentation for ensuring privacy, confidentiality
and justice issues
 The ethical review should be done through formal meetings and
should not resort to decisions through circulation of proposals
 Decisions are preferably arrived at by consensus

 The IEC’s member secretary shall screen the proposals for their
completeness and depending on the risk involved categorize them
into:
- Full review
- Expedited review
- Exempted from review

FULL REVIEW
All research proposals presenting with more than minimal risk.
Projects that involve vulnerable population (children, psychiatric
patients etc.,)
Full review is carried out in cases involving
(a) collection of blood samples
(b) Prospective collection of biological specimens eg. Skin
appendages, excreta, saliva, placenta, amniotic fluid, sputum etc.

EXPEDITED REVIEW
 Those with no more than minimal risk to research participants
may be subjected to this review
1. Minor deviations from originally approved research.
2. Revised proposal previously approved through full review by the IEC
or continuing review of approved proposals
3. Clinical studies of drugs and medical devices only when -
- research is on already approved drugs except when studying drug
interaction or conducting trial on vulnerable population
- adverse Event (AE) or unexpected Adverse Drug Reaction
(ADR) of minor nature is reported.

EXEMPTED FROM REVIEW
 Proposals with less than minimal risk
 Research on educational practices such as instructional
strategies or effectiveness of or the comparison among
instructional techniques, curricula, or classroom management
methods.

Following are considered for ethical review
 Scientific design and conduct of study
 Recruitment of Research Participants
 Care and Protection of Research Participants
 Protection of research participant confidentiality
 Informed Consent Process

SCIENTIFIC DESIGN AND CONDUCT OF
STUDY
 Appropriateness of study design
 Statistical methodology including sample size
calculation
 Risk vs anticipated benefits for research participants.
 Justification for Controls used
 Withdrawal criteria of participants
 Criteria for termination of trial
 Adequacy of monitoring and auditing the conduct of
research.
 Site facilities for handling emergencies.
 Reporting and Publication issues

RECRUITMENT OF RESEARCH PARTICIPANTS
 Study population – demographic characteristics
 Means by which participants are contacted and
recruited.
 Means by which full information is conveyed to
research participants or their representatives
 Criteria for recruitment
Inclusion criteria
Exclusion criteria

CARE AND PROTECTION OF RESEARCH
PARTICIPANTS
 Suitability of investigator qualifications and experience for
proposed study.
 Medical care to be provided to participants during and
after research.
 Adequacy of medical supervision
 Steps taken if participants voluntarily withdraw from study
 Informed consent
 Insurance and indemnity arrangements

PROTECTION OF RESEARCH PARTICIPANT
CONFIDENTIALITY
 Description of persons who will have access to personal data
of research participants, including medical records and
biological samples.
 Measures taken to ensure the confidentiality and security of
personal information concerning research participants.

INFORMED CONSENT PROCESS
 Adequacy, completeness and understandability of written and
oral information given to participants or their legal
representatives
 Clear justification for intention to include research
individuals who cannot consent
 Assurance that participants will receive any new information
that becomes available
 Contact details of persons whom the participants need to
contact for any complaints or queries.

DECISION
 Out right approval (at most, only very minor changes are
suggested. The application contained all necessary
information.)
 Approval with modifications (there is enough
information to judge the study, but clarification or
changes are needed)
 Resubmit with more information (there is not enough
information to judge the application appropriately
 Outright disapproval (there is no way the researcher can
ethically do study)

RECORDS
○ Constitution & composition of IEC
○ CV of all members & records of training
○ SOPs of the IEC
○ National & International guidelines
○ Copies of protocol submitted for review
○ All correspondence with IEC members and Investigators
regarding application, decision and follow up.
○ Agenda of all IEC meetings and Minutes signed by chairperson
○ Copies of decisions communicated to applicants
○ Notifications issued for premature termination of study
○ Final report of the study
○ All records must be safely maintained after
completion/termination of study for 3 years.

REVIEW PROCESS
Periodic Review:
 Ongoing research may be reviewed at regular intervals of six months
to one year
Continuing Review:
 The IEC has the responsibility to continue reviewing approved
projects for continuation, new information, adverse event monitoring,
follow up.
Interim Review:
 Interim Review – decide special circumstances for review by sub-
committee – re-examination of proposal already examined by IEC.

IEC : CHALLENGES
 Inadequate or no standard operating procedures (SOPs)
 Noncompliance with the Schedule Y recommendations
 Lack of trained manpower
 Heavy workload.
 Inadequate space allocated for EC operations
 Lack of administrative support, and inadequate remuneration offered
to members serving on EC boards.
 No legal experts.
 Poor record keeping.
 Many EC members are ambiguous about their roles and
responsibilities, during a review process
 The failure to conduct internal audits
 Absence of accreditation

ACCREDITATION AGENCIES
 AAHRPP
 SIDCER
 The Association for the Accreditation of Human Research
Protection Programs (AAHRPP) is an independent accrediting body
that works to protect the rights and welfare of research participants
and promote scientifically meritorious and ethically sound research.
 The Strategic Initiative for Developing Capacity in Ethical Review
(SIDCER) is a network of independently established regional fora
for ethical review committees, health researchers and invited
partner organizations with an interest in the development of ethical
review.

SIDCER- It has developed out of the capacity-building activities of WHO/TDR in
cooperation with the national and international research organizations
SIDCER formally began through the formation of these fora.
 FECCIS
 FERCAP
 FLACEIS
 FOCUS
 PABIN
Partner organizations
 MFES
 GCPA
 ICMR
 WHO/TDR
 PATH

FERCI
 Forum for Ethics Review Committees in India
 National chapter of FERCAP
 Constituted in 2002
 Registered in 2006
 Accounts set up in 2007
 FERCI operates in close collaboration with important
institutions like the World Health Organization (WHO), Indian
Council of Medical Research (ICMR), Central Drugs Standard
Control Organization (CDSCO), FERCAP, SIDCER

INFORMED CONSENT
 The concept of “Informed Consent” for participation in research was first
recorded in 1900 but it was Nuremberg code in 1947 that first highlighted the
essentiality of voluntariness of this consent.
 Declaration of Helsinki further stated it as being essential but it also allows
physicians under special circumstances to use subjects without giving informed
consent.
 Various clinical research guidelines require that every adult volunteer must agree
to participate in writing before enrollment in a trial.
 Key elements of informed consent : Information, Comprehension,
Voluntariness, Decision making capacity.

INFORMED CONSENT
 Written consent is required from each study subject.
 Information should be given verbally as well as using a ‘patient information sheet’.
 Consent must be obtained in writing using ‘Informed Consent Form’.
 Both should have been approved by the ethics committee and furnished to the
Licensing Authority.
 Any changes in the informed consent documents should be approved by the ethics
committee and submitted to the Licensing Authority.
 Where a subject is not able to give informed consent, the same may be obtained from
a legally acceptable representative
 If the Subject or his/her legally acceptable representative is unable to read/write – an
impartial witness should be present during the entire informed consent process.

Checklist for study Subject’s informed consent documents
Essential Elements:
 Statement that the study involves research and explanation of the purpose
of the research
 Expected duration of the Subject's participation
 Description of the procedures to be followed
 Description of any risks or discomforts to the Subject
 Description of any benefits to the Subject
 Disclosure of specific appropriate alternative procedures or therapies
available to the Subject.
 Statement describing the extent to which confidentiality of records
identifying the Subject will be maintained and who will have access to
Subject’s medical records

 Trial treatment schedule(s) and the probability for random assignment to
each treatment (for randomized trials)
 Compensation and/or treatment(s) available to the Subject in the event of a
trial-related injury
 An explanation about whom to contact for trial related queries, rights of
Subjects and in the event of any injury the anticipated prorated payment, if
any, to the Subject for participating in the trial
 Subject's responsibilities on participation in the trial
 Statement that participation is voluntary, that the subject can withdraw from
the study at any time and that refusal to participate will not involve any
penalty or loss of benefits to which the Subject is otherwise entitled

Additional elements
 a. circumstances under which the Subject's participation may be terminated by
the Investigator without the Subject's consent.
 b. Additional costs to the Subject
 c. The consequences of a Subject’s decision to withdraw from the research and
procedures for orderly termination of participation by Subject.
 d. Statement that the Subject or Subject's representative will be notified in a timely
manner if significant new findings develop during the course of the research which
may affect the Subject's willingness to continue participation will be provided.
 e. A statement that the particular treatment or procedure may involve risks to the
Subject (or to the embryo or fetus, if the Subject is or may become pregnant)
 f. Approximate number of Subjects enrolled in the study

Informed Consent Form
Study Title:
Study Number:
Subject’s Initials: _______________ Subject’s Name:_______________
Date of Birth / Age: _________________
(Subject)
(i) I confirm that I have read and understood the information sheet
dated ___ for the above study and have had the opportunity to
ask questions. [ ]
(ii) I understand that my participation in the study is voluntary and
that I am free to withdraw at any time, without giving any
reason, without my medical care or legal rights being affected. [ ]
(iii) I understand that the Sponsor of the clinical trial, others
working on the Sponsor’s behalf, the Ethics Committee and the
regulatory authorities will not need my permission to look at
my health records both in respect of the current study and any
further research that may be conducted in relation to it, even if
I withdraw from the trial. I agree to this access. However, I
understand that my identity will not be revealed in any
information released to third parties or published. [ ]
(iv) I agree not to restrict the use of any data or results that arise
from this study provided such a use is only for scientific
purpose(s) [ ]
(v) I agree to take part in the above study. [ ]
Signature (or Thumb impression) of the Subject/Legally Acceptable Representative:_____________
Date: _____/_____/______
Signatory’s Name: ______________________________________________________
Signature of the Investigator: ____________________________ Date: _____/_____/______
Study Investigator’s Name: __________________________________________________
Signature of the Witness ______________________ Date:_____/_____/_______
Name of the Witness: _______________________________________________________

CONCLUSION
 ECs continue to play an important role in the ethical conduct of
clinical research. However, ECs as a system are facing challenges
with paucity of trained experts and lack of supervising national
body. This calls for a strong need to focus on capacity building and
establishment of an efficient central body to include all ECs under
its umbrella to bring transparency and accountability in their
functioning. Combined efforts by DCGI, ICMR and individual
ECs will definitely promote a sound culture of clinical research.

Institutional ethics committee & informed consent

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