From history and with case studies

1. INSTITUTIONAL REVIEW BOARD
(IRB)
(OR)
INDEPENDENT ETHICS COMMITTE
(IEC)
Presented by,
BALADATTA SAI. CHINTAM
17AB1R0019
VIGNAN PHARMACY COLLEGE
GUNTUR, ANDHRAPRADESH.

2. INTRODUCTION
 Experimentation on human being is subject to ethical
standards that promote respect for all and protect their
health and rights.
 The “Institutional Review Board” (IRB) is a local
administrative body established to protect the rights, safety
and well-being of human research subjects recruited to
participate in a clinical research.
 The IRB has the authority to approve, require modification
in, or disapprove all research activities that fall within its
jurisdiction.
 The IRB provides assurances to research subjects that every
reasonable attempt has been made to protect their rights and
safety as subjects.

3. WHY DO WE NEED IRB?
 The IRB is in place to uphold the three principles of the
Belmont report :
 PRINCIPLE 1: Respect for persons.
 voluntary participation.
 Privacy and confidentiality protected.
 PRINCIPLE 2: Beneficence
 Risks are minimized.
 Conflicts of interest managed adequately.
 PRINCIPLE 3: Justice
 Vulnerable subjects not targeted because of convenience.
 People likely to benefit from research are not systematically
excluded.

4. HISTORY
 Formal review procedures for institutional human subjects
studies wre orginally developed in direct reponse to
research abuses in the 20th century.
 Among the most notorious of these abuses were the
experiments of nazi physcians during world war-II.

5. HISTORY
 The Tuskegee syphilis study , a long term project
conducted between 1932 to 1972 by the U.S. public
health service.

6.  Numerous human radiation
experiments conducted during the
cold war, one of them is Stanford
prison experiment.
 Project MKULTRA is a code
given to the experiments
conducted by CIA.

7. DECLARATION OF HELSINKI
 The result of these abuses was the National Research Act
of 1974 has developed the Declaration of helsinki as a
statement of ethical priciples to provide guidance to
physcians and other participants in medical research
involving human subjects.
PRINCIPLES:
1. It is the duty of the phyiscian in medical research to
protect the life, health, privacy and dignity of the human
subject.
2. Medical research involving human subjects must conform
to generally accepted scientific principles.

8. DECLARATION OF HELSINKI
 The design and performance of each experimental procedure
involving human subjects should be clearly formulated in an
experimental protocol.
 Independent committee should be in conformity with the
laws and regulations of the country in which the research
experiment is performed. the committee has the right to
monitor ongoing trials.
 Medical research involving human subjects should be
conducted only by scientifically qualified persons under the
supervision of a clinically competent medical person.
 Physcians should cease any investigation if the risks are
found to outweigh the potential benefits or if there is
conclusive proof of positive and benificial results.

9. CONSTITUTION OF IRB
 The IRB should consist at least seven members, who
collectively have the qualifications and experience to
review and evaluate the science, medical aspects, and
ethics of the proposed trial. Viz;
a) Chairperson-Appointed (from outside the institution)
b) 1-2 basic medical scientists
c) 1-2 clinicians from various institutes
d) One legal expert or retired judge
e) One social scientist
f) One philosopher or ethicist
g) Secretary member

10. QUORUM OF IRB
 For reviewing and making decision on each protocol the
quorum of IRB should be atleast five members with the
following representations;
1) Basic medical scientists (preferably one pharmacologist)
2) Clinicians
3) Legal expert
4) Social scientist/Representative of non-governmental
voluntary agency/philosopher/ethicist/theologian
5) Lay person from the community
6) Further, based on the requirement of research area (AIDS,
genetic disorders etc…) specific patient groups may also
be represented in the IRB

11. FUNCTIONS AND OPERATIONS OF IRB
 Only those IRB members who are independent of the
clinical trial and the sponsor of the trial should vote/provide
opinion in matters related to the study.
 Only members who participate in the IRB/IEC review and
discussion should vote/provide their opinion and advice.
 The IRB should perform its functions according to written
records of its activities and minutes of its meetings, and
should comply with GCP and with the applicable regulatory
requirements.
 The investigator may provide information on any aspect of
the trial, but should not participate in the deliberations of
the IRB or in the vote/opinion of the IRB.

12. FUNCTIONS AND OPERATIONS OF IRB
 The IRB should establish, document in writing, and
follow its procedures, which should include
 Determining its composition (names and qualifications of
the members)
 Scheduling, notifying its members of, and conducting its
meetings
 Conducting initial and continuing review of trials
 Determining the frequency of continuing review, as
approprite

13. FUNCTIONS AND OPERATIONS OF IRB
 Specifying that no subject should be admitted to a trial
before the IRB issues its written approval/favorable
opinion of the trial.
 Specifying that no deviations from, or changes of the
protocol should be initiated without prior written IRB
approval/favorable opinion of an appropriate amendment,
except when necessary to eliminate immediate hazards to
the subjects or when the changes involves only logistical
or administrative aspects of the trial.
 specifying that the investigator should promptly report to
the IRB.

14. FUNCTIONS AND OPERATIONS OF IRB
 Deviations from, or changes of the protocol to eliminate
immediate hazards to the trial subjects.
 Changes increasing the risk to subjects and affecting
significantly the conduct of the trial.
 All adverse drug reactions that are both serious and
unexpected.
 New information that may effect adversely the safety of
the subjects or the conduct of the trial.

15. RESPONSIBILTIES OF IRB
 An IRB should safeguard the rights, safety and well-being
of all trial subjects.
 The IRB should obtain the following documents.
a) Subject recruirtment procedures (eg: Advertise).
b) Written information to be provided to subjects.
c) Investigator’s Brochure (IRB).
d) Available safety information.
e) Information about payments and compensation.
f) Investigator’s current curriculum vitae.
g) Any other may need to fulfill its responsibilities.

16. RESPONSIBILITIES OF IRB
 The IRB/IEC should continuing review of each ongoing
trial at intervals appropriate to the degree of risk to human
subjects, but at least once per year.
 The IRB may request more information than is given to
study subjects when, in the judgement of the IRB the
additional information would add meaning to the
protection of the rights, safety and/or well-being of the
subjects.
 The IRB should review both the amount and method of
payment to subjects to assure neither compulsion nor
undue influence on the trial subjects.

17. RESPONSIBILTIES OF IRB
 Payments to a subject should be prorated (day basis) and
not wholly contingent on completion of the trial by the
subject.
 The IRB should ensure that information regarding payment
to sujects, including the methods, amounts, and schedule
of payment to trial subjects, is set forth in the written
informed consent from an any other written information to
be provided to subjects

18. TYPES OF REVIEWS IN IRB
 The IRB’s member secretary shall screen te proposals for
their completeness and depending on the risk involved
categorize them into;
 EXEMPT REVIEW
Includes anonymous surveys.
 EXPEDITED REVIEW
Includes interviews and surveys.
 FULL BOARD REVIEW
Includes any work with vulnerable populations,
involving sensitive questions etc........

19. EXEMPT REVIEW
 If the proposed research inolves less than minimal risk to
participants and involves any of the following, it may qualify
for exempt status.
a) Research conducted in established or commonly accepted
educational institutions that specifically involves normal
education practices that are not likely to adversely impact
students opportunity to learn required educational content.
b) Research that only includes interactions involving
educatinal tests, survey procedures, interview procedures or
observation of public behaviour.
c) Taste and food quality evaluation and consumer acceptance
studies.

20. EXPEDITED REVIEW
 If the proposed research presents no more than minimal risk,
does not involve any vulnerable populations like children,
prisoners, individuals with impaired decision making
capacity and economically or educationally disadvantaged
persons. and involves any of the following, it may qualify for
Expedited review.
a) Collection of data from voice, video, digital or image
recordings made for research purposes.
b) Collection of data through noninvasive procedures routinely
employed in clinical practice (X-rays).
c) Research involving already approved drugs.
d) When an adverse event or unexpected adverse reaction is
reported.

21. FULL BOARD REVIEW
 All research proposals presenting with more than minimal
risk requires full board review.
a) Projects that involves vulnerable population.
b) Collection of blood samples.
c) Prospective collection of biological specimens like sputum,
skin appendages, excreta, saliva, amniotic fluid.
d) Procedures that might cause significant psychological or
emotional distress.
e) Collection of information about highly sensitive topics.
f) Collection of information that could seriously harm the
participant legally, socially, financially etc...

22. DECISIONS OF IRB
 Out right approval ( at most, only very minor changes are
suggested. The application contained all necessary
information)
 Approval with modification ( 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 to study)

23. INFORMED CONSENT FORM
 A major component of GCP is the method by which the
researchs will obtain voluntary and informed consent from
subjects.
 Informed consent is a process, not just a form.
 Information must be presented to enable persons to
voluntarily decide whether or not to participate as a
research subject.
 The procedures used in obtaining informed consent should
be designed to educate the subjects population in terms that
they can understand.

24. INFORMED CONSENT FORM
 In seeking informed consent the following information
should be provided to the subject.
 Statement that the study involves research and explanation
of the purpose of the research.
 Expected duration of the subjects participation.
 Description of the procedures to be followed, including all
invasive procedures and,
 Description of any reasonably risks or discomforts to the
subject.
 Description of any benefits to the subject or others
reasonably expected from research. if no benefit expected
subject should be made aware of this.

25. INFORMED CONSENT FORM
 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 subjects medical records.
 Trial treatment schedule and the probability for random
assignment to each treatment (for randomized trials).
 Compensation and or treatments 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.

26. INFORMED CONSENT FORM
 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.

27. INFORMED CONSENT FORM
 Any other pertinent information which may be required, viz;
a) Statement of foreseeable circumstances under which the
subjects participation may be terminated by the investigator
without the subject’s consent.
b) Additional costs to the subject that may result from
participation in the study.
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 by subject.
e) Approximate number of subjects enrolled in the study.

28. INDIAN SCENARIO
 The DCGI is responsible for regulatory approvals for the
conduct of clinical trials in India which is governed by the
rules in Amended in Schedule Y. Standard operating
procedures for IRB’s are prepared by ICMR.
 ICMR codes-general principles
1. Essentialiy.
2. Non-Exploitation.
3. Privacy and Confidentiality.
4. Accountability and Transparency.
5. Precaution and Risk minimization.
6. Professional Competence.

29. EC’S IN INDIA-PAST
 The requirement for an EC to oversee clinical research was
first made in the ICMR policy statement for ethics published
in 1980.
 Several challenges including inadequate formal training,
contribution from non-tehnical members, administrative
support as well as no SOP’s and a heavy workload were
identified.
 In the absence of regulatory oversight of EC’s the
introduction of the clinical trial registry India (CTRI) and self
reguation through voulntary accreditation programmes
brought a measure of accountability and transparency.

30. EC’S IN INDIA-PRESENT
 The years after 2013 brought much transparency and some
contol over the constitution and functioning of EC’s which
were also entrusted with increasing responsibilty in
regulatory trials.
 The major milestone in the history of EC’s in India was the
requirement of registration with Central Drugs Standard
Control Organizaton (CDSCO).
 As on august 1, 2016, there were 1083 Registered EC’s of
which 841 were institutional and 242 were independent.
 Maharashtra has the highest number of EC’s (259) and the
least is 1 in sikkim. AP and telangana has 69 EC’s.

31. CASE STUDY-1
 The first case concerned with the widely publicised
demonstration project of the human papilloma virus (HPV)
vaccine in 2009.
 Participants in this large project were teenage girls from
urban and rural backgrounds living in hostels.
 A major concern with this study as that informed consent was
provided by school heads and hostel wardens in place of
assent from the girls and consent from their parents or legally
authorized representatives.
 Parents of the non-resident students could not understand the
contents of the brochures and assumed the project as a
government intiative.
 The final result of the study is death of six girls.

32. CASE STUDY-2
 Case described a patient who had been taking a low cost standard
treatment for a chronic condition before being enrolled in a study.
 Because he was feeling better he requested that he be kept on the
study drug for a longer period of time but the investigator told him
this was not possible. The patient died shortly afterwards.
 The main concern arising from this study was about post-study
access to treatments and whether the participants should have
longer access to the study drug when the drug is not yet licensed
and has not passed all safety tests for long term use.
 Alternatively should such patients be provided with a given
standard of care for a specified period of time ? should that be a
strandard part of a study protocol ?

33. CASE STUDY-3
 Bhopal gas tragedy survivors in covaxin clinical trials.
 Many of these participants were not aware that they are
participating in a drug trail. and atleast tn serious adverse
reactions were noted.No informed consent was sought.

34. CONCLUSION
 There has been a clear spurt in the number of clinical trials
being conducted in India.
 The number of applications recieved by DCGI and IRB’s
makes it evident that the clinical trial industry is growing in
India.
 India’s advantages over it’s counterparts are the availability of
large multi-ethnic and drug-native patient population, rapid
patient recruitment, cost-effective location when compared to
western countries.
 Keeping in mind the rapid growth in clinical trials, EC’s and
regulatory bodies in India have been streamlining the
processess to protect the well being and the rights of the
research participants.

35. CONCLUSION
 Keeping the future and the stringent quality requirements in
mind the Indian regulatory bodies work in par with other
governing bodies in par with other governing bodies like
ICMR, DBT and AERB in association with agencies like
FICCI, FERCAP and SIDCER
 India is today identified as a major resource centre for
conducting trials due to its increased regulatory control.
 Further investments in the ethical review system and training
of clinical invsetigators may assist in improving the level of
quality in India’s clinical trial system and build the capacity
needed for India to participate in the growing international
clinical resarch bussiness.