Introduction

Clinical

trial

experiments

Such prospective biomedical

or

are

behavioral

done

in

clinical

research.

research

studies

on human

participants are designed to answer specific questions about biomedical or

behavioral

interventions,

including

new treatments (such

as

novel vaccines, drugs, dietary choices, dietary supplements, and medical devices)
and known interventions that warrant further study and comparison. Clinical trials
generate data on safety and efficacy.
An institutional review board (IRB), also known as an independent ethics
committee (IEC), ethical review board(ERB), or research ethics board (REB), is a
type of committee used in research in the United States. They often conduct some
form of risk-benefit analysis in an attempt to determine whether or not research
should be done.[1] The purpose of the IRB is to assure that appropriate steps are
taken to protect the rights and welfare of humans participating as subjects in a
research study.
The first appearance of need of ethics committee (EC) was made in Declaration of
Helsinki in 1964, while in India it appeared in 1980 in the ICMR Policy Statement.
EC also called as the Institutional Review Board or the Ethics Review Board
stands as the bridge between the researcher and the ethical guidelines of the
country. ECs are responsible for carrying out the review of proposed research
before the commencement of the research. The basic responsibility of EC is to
ensure an independent, competent and timely review of all ethical aspects of the
project proposals received in order to safeguard the dignity, rights, safety and wellbeing of all actual or potential research participants.

ETHICS AND BIOETHICS

Ethics also known as moral philosophy seeks to address philosophical
questions about morality. Its history goes back to philosophy and religious
writings. Bioethics is the philosophical study of ethical controversies brought about
by advances in biology and medicine. Bioethics concerns ethical issues that arise in
relationships among life sciences, biotechnology, medicine, politics, law,
philosophy and theology. The modern field of bioethics first emerged as an
academic discipline in the 1960

Ethical Codes The Declaration of Helsinki

The first set of ethics rules for research in humans formulated by the
international medical community was established in 1964 by the World Medical
Association (WMA), in the Declaration of Helsinki (Declaration). The WMA is an
international organization representing physicians and was founded in 1947. The
organisation was created to ensure the independence of physicians and to work for
the highest possible standards of ethical behaviour and care among them, at all
times. The Declaration includes a number of important human research ethics
codes of practice. However, the Declaration is still a very short document, covering
only five pages. It defines ethical principles, but provides little guidance on the
governance, operation and responsibilities of a human ethics committee (Ethics
Committee, EC). The Declaration is not a legally binding instrument in
international law. Rather, its authority is drawn from the degree to which it is
codified or influences national or regional legislation and regulations. The
Declaration should be seen as an important human research guidance document,

but it cannot overrule local regulations and laws. There have been several updated
versions with the last accepted at the 59th WMA General Assembly in Seoul,
South Korea in 2008.

Ethics Committee
An EC reviews and subsequently approves or rejects research protocols
submitted by investigators/researchers (investigators). There are different kinds of
ECs. Some review protocols for animal studies, some for human studies in social
sciences such as psychology and education, and others for clinical trials in patients
or healthy volunteers. In this Guide, we address only the principles of ethics review
of protocols involving interventional studies or clinical trials in humans. Many
countries require and legally enforce approval by an EC before clinical trials can
be initiated for testing new drugs or vaccines, medical devices, diagnostics and
medical procedures referred to as test article in this Guide.
As stated in the Declaration of Helsinki: The research protocol must be
submitted for consideration, comment, guidance and approval to a research ethics
committee before the study begins. The ICH GCP states: A trial should be
conducted in compliance with the protocol that has received prior institutional
review board (IRB)/independent ethics committee (IEC) approval/favorable
opinion.
Different names are used for ethics committees reviewing human clinical
trial protocols, such as ethics committee (EC), research ethics committee (REC) or
institutional review board (IRB). For simplicity in this Guide, we use the term
Ethics Committee and the corresponding abbreviation EC. Regardless of the term

chosen for an individual EC, each operates in accordance with applicable laws and
regulations. We also need to clarify that most ECs review study protocols for a
single institution, such as a hospital, with or without academic affiliation, while
some are centralised, and review protocols from more than one institution/clinic.
Central ECs are designed to help reduce administrative burdens on local
ECs and investigators, while maintaining a high level of protection for human
research participants. This arrangement is especially useful when the investigator
works from a single physicians private practice or when multiple sites are
involved in the same geographical or judicial region. However, whether local or
centralised, ECs should all operate at the same standard.
A human research ethics committee EC should not be confused with any
hospital ethics committee (HEC) reviewing ethical or moral questions that may
arise during a patient's standard care. The EC reviews clinical research protocols,
while the HEC acts as the patients advocate, defining the ethical principles of
clinical procedures and management within a hospital.

Why do we need Research Ethics Committees (RECs)?

The Department of Health requires that research is reviewed independently
to ensure it meets the required ethical standards
RECs review research proposals in order to:
1. Protect research participants
2. Facilitate and promote good quality research

3. Protect researchers
4. Enable researchers to obtain funding
5. Enable research to be published

An example of the composition of a Research Ethics Committee

Hospital Consultants
General Practitioner
Nurse/Midwife
Clinical Psychologist
Pharmacist
Public Health Physician
Social Scientist
Statistician
Lay members

Roles of Ethics Committee

Ethics as much talked about, is arduous to understand and interpret. One

always tries to interpret ethics in his or her own way. So how can we justify as to
what is ethical and what not? Seems like a real googly, isnt it? In similar sense,
think about how ethics committees justify their decisions with regards to new
clinical trials, subject safety etc. To understand the role of ethics committee (EC),
we need to step in its shoes. However, still the question remains, how do they do
it?
There is a normal way, which is to follow the guidelines, the regulations and may
be as a matter of fact, Standard operation procedures (SOPs). Well inspite of all
righteous compliance we may be far from achieving an ethical outcome.

Arduous role of Ethics Committee

According to Mark P. Aulisio and Robert M. Arnol in their article on Role of the
Ethics Committee they quoted Ethics committees arose in response to a clinical
need for a formal mechanism to address some of the value conflicts and
uncertainties that arise in contemporary health-care settings

Basic role of Ethic Committee can be summed as:

To

protect

the

rights,

safety

and

well

being

of

patients;

by

Prevent studies that pose an unacceptable risk of harm to participants

 Ensure that all participants in research are aware about the pros and cons for their
participation and have given appropriate Informed Consent.

To promote fair ethical policies and procedures which will maximize the
likelihood of achieving good and patient-oriented outcomes;

To enhance the ethical tenor between health care professionals and organisations
conducting clinical trials.

Overview and monitor thoroughly, compliance of sites with Standard Operating

Procedures (SOPs), regulations, guidelines and ETHICS.

Offering due consideration to community views.

Responsibilities
Review of proposed research before the commencement of the research
Independent, competent and timely review of all ethical aspects of the
project proposals received.
Safeguard the dignity, rights, safety and well- being of all actual or potential
research participants

 The appropriateness of the study design in relation to the objectives of the

study.
The statistical methodology (including sample size calculation).
The potential for reaching sound conclusions with the smallest number of
research participants should be assessed. Responsibilities
The EC should also look into matters like Informed consent process
Qualifications of Principal investigator and supporting staff, adequacy of
infrastructure and facilities,
Risk benefit ratio, plans to maintain confidentiality and plans for post trial
access and compensations.
They also need to ensure that there is regular evaluation of the ongoing
studies
EC is the most important check point for promoting ethical research in the
country

Ethical Considerations
Basic Ethical Principles in Human Research
The Belmont Report (1974) summarizes three basic ethical principles relevant to
research involving human subjects.

 Respect for persons

Beneficence
Justice

Respect for Persons

Individuals should be treated as autonomous agents
The investigator must ensure that the subject has received a full disclosure of the
nature of the study, the risks, benefits and alternatives, with an extended
opportunity to ask questions.
Persons with diminished autonomy are entitled to protection Persons with
diminished autonomy (e.g., prisoners, students, children, etc) should not be
coerced to participate in a research

Beneficence
Maximize possible benefits and minimize possible harms
The investigator should give forethought to the maximization of benefits and the
reduction of risk that might occur from the research

Justice
Fairness in distribution

 Justice occurs when some benefit to which a person is entitled is denied without
good reason or when some burden is imposed unduly
Equitable selection of participants

Clinical Trials in the Context of Biomedical Research

Biomedical research can be sub-classified as basic/pre-clinical research and
clinical research (see illustration). Pre-clinical biomedical research is important for
expanding the knowledge of basic biological mechanisms. Studies are commonly
conducted in pre-clinical departments or institutions in fields such as anatomy,
biochemistry, cellular biology, immunology, microbiology, molecular biology,
neuroscience, pharmacology and physiology. Pre-clinical research can contribute to
the discovery of new medical treatments. Clinical research ranges from clinical
laboratory or investigational studies to testing of new clinical procedures, new
clinical diagnostic tools and new medicinal products in humans.

Low and High Risk Clinical Trials

Three essential factors echo the risk of harm level of a clinical trial:
cumulative clinical experiences of the test article, targeted participant population
and biological characteristics of the test article. As clinical testing proceeds, more
and more participants are exposed to the test article. The information gathered is
used to evaluate the effects negative as well as positive of the product in
humans. Accordingly, it follows that risk of harm in general is much higher during
the initial clinical testing phase, i.e., human pharmacology, than during later stages.
Thus early phase clinical trials often need more oversight than later phase trials.

The highest level of risk arises when the product is first tested in humans (firstintohuman trials), followed by trials with dose escalation and multiple dosing.
Most of these trials are conducted in healthy volunteers, not participants with the
target disease. Initial human pharmacology clinical trials, conducted mostly on
healthy volunteers, are followed by exploratory trials where the test article is
administered on target participant groups for the first time. The reactions from
these participants may differ from those in healthy volunteers, so first-into-human
trials are also often regarded as having a higher risk of harm and therefore need
extra oversight
Clinical testing of medicinal products that are ineffective and/or have
unreasonable side-effects is terminated early. This means that late exploratory and
confirmatory clinical trials are performed on a subsample of products confidently
expected to have a reasonably low risk of inducing side-effects in relation to the
treatment effect, since the safety profile is acceptable. The targeted patient
population may also influence the degree of risk of a medicinal product. For
instance, life-threatening diseases such as cancer usually call for stronger and thus
potentially more toxic drugs with a different risk of harm acceptance from, for
instance, anti-flu drugs. Likewise, young children may have a higher risk of sideeffects than adults, due to their ongoing organ growth and the bodys functional
development in early life. Participants in need of multiple drug treatments, such as
psychiatric patients or drug abusers, have a risk of harm from drug-to-drug
interaction, which may be higher than for participants given the test drug who have
no other significant medical conditions. Proper risk assessment of a trial can be
made only with detailed access to the results of previous testing of the product, in
animals and humans, as well as details of the target population and knowledge
about the characteristics of the test article. Such information should be included in

any trial protocol. For trials overseen by a regulatory authority, additional details
are documented in a mandatory investigators brochure. Both the trial protocol and
the investigators brochure for a trial, if present, should be submitted to an EC for
review

Sponsors of Clinical Trials

Sponsors of a clinical trial can be either a commercial company (industrysponsored trial) or a clinical investigator/physician (non-industry trial). The former
comprises pharmaceutical and biotechnology companies, while the latter comprises
medical schools, biomedical research institutes, government institutions or clinical
trial networks. Depending on the body, non-industry trials are referred to as nonprofit, nonindustrial-sponsored, investigator-initiated, or institutional-initiated
trials. The large majority of industry-sponsored clinical trials are registered with
the US national clinical trials registry (http://www.ClinicalTrials.gov), because
registration is a mandatory requirement by the US government for filing a new
drug application in the US. The US trials registry includes more investigatorinitiated than industry-sponsored trials, although the former are registered
predominantly by US investigators. Globally, there are many more investigatorinitiated than industry-sponsored clinical trials. The overall objective of a
commercial life-science company in conducting clinical trials on a medicinal
product is to collect information about the safety and efficacy of the product in
human participants, i.e., to take the test article from pre-clinical discovery and
testing to usage.

The data collected and analyzed from trials eventually represent an

important and mandatory body of information for the application to a government
drug regulatory authority for market acceptance of the product. The commercial
company is therefore concerned that the trial follows international and local
regulations from scientific, ethical and quality assurance viewpoints so
government market approval can be achieved in a timely and undisputed manner.
The main objective here is thus primarily commercial. In contrast, an investigator
acting as sponsor of a clinical trial may primarily be involved for scholarly
reasons, rather than to bring a new medicinal product to the market. Often, the
investigators motive is scientific achievement, leading to published findings,
advancing knowledge among peers, and many times also improvement of patient
care, health care or population health. Such trials may compare new surgical
procedures, health interventional programmes or clinical diagnostic tools. They
may also test combination therapies or new indications of already approved
commercial medicinal products. A smaller number of investigator-initiated trials
test new medical products that an investigator or institution has invented, with the
primary objective being commercial. Whether the sponsor of a clinical trial is a
commercial or non-commercial body, the same scientific, ethical and quality
standards should apply, and the EC review process should be identical. Industrysponsored trial protocols have commonly been subject to third-party review
because the clinical development plan of products is continuously monitored by
drug regulatory authorities. Investigator-initiated trials, on the other hand, may lack
the review of an independent third party before they are submitted to the EC. The
EC may request details of the third-party review and details of the protocol
development team. Regardless of who the sponsor may be, the clinical trial
protocol should detail the same aspects: the scientific rationale behind the protocol,

the rationale behind the trial design and sample size, treatment blinding, the riskbenefit balance, participant compensation, informed consent, insurance/indemnity,
any conflicts of interest that may influence the collection of data or results, and
essential quality assurance measures.

Issues of Ethics of Clinical Trials:

Informed consent process.

Vulnerable participants.
Privacy and confidentiality.
Data safety monitoring.
Participant recruitment procedures
Qualification of investigators
Conflict of interest.
Clinical trial insurance and indemnity.
Essential clinical trial documents.
Clinical trial registration
Dissemination of trial results.
Issues of EC Procedures: Local laws and institutional guidelines.

 Proportionate EC review.
Expedited/full board review.
Continuing review.
Acceptability of trial.
Trial amendments.
Adverse event reporting.
Anticipated problems.
Suspension or termination of a trial.
Complaints.
Appeals.
Non-compliance

Qualification of Investigator Scenarios

Qualification of Investigator - Scenario 1
Dr. Yu Lung Wong is a certified traditional medicine practitioner in Clear
Water Bay in Hong Kong. His clinic is very popular among the local residential
population, so popular that he has not been able to take a break for a single day

during the past year. His nickname among the locals is in fact Seven to Eleven.
Despite this heavy workload, he has agreed to be the investigator of an herbal
extract oncology trial sponsored by a local herbal medicine company, Golden
Trust. He will recruit the cancer patients through his own clinic. Dr. Wong has
finally completed the EC application and will now send it to the EC of a local
medical teaching institution where he is a temporary lecturer.

Qualification of Investigator - Scenario 2

Mr. Christopher Lindbergh is the chief pharmacist at a university-affiliated
hospital, and he is fascinated with vaccines and their development. He has
previously been involved in several vaccine trials but only as the co investigator.
During the past year, he has written a trial protocol himself, aiming to study the
effect of an oral flu vaccine in combination with an injectable flu vaccine. One is
produced by a US company and the other by a UK company, and both companies
have decided to provide their vaccines free of charge. Mr. Lindbergh has also been
fortunate to get enough financial support from the local airline company, Spirit
Space. Two pediatricians in his hospital are willing to act as co-investigators. Mr.
Lindbergh is of course very pleased when he drops his EC application into the
application mailbox at the local EC office, thinking: I will become the principal
investigator. YES!

Investigator Qualification - Scenario 3

Dr. Susanna Black is the head of the department of nursing at an Australian

medical school. She is a nurse by training and she acquired her PhD degree five
years ago in the UK. Dr. Black has been able to secure a research grant from the
Health Promotion Research Fund for an interventional quit smoking randomized
clinical trial. The trial will have two groups of current smokers; one group will be
followed without intervention, and the other will be given educational information
by means of lectures, videos and brochures. Dr. Black enters her office and finds a
brown envelope on her desk. She opens it. Dr. Black is very surprised when she
reads: The ethics committee has after much consideration not approved your
application as it stands

Institutional Ethics Committee

It is mandatory, as per the Chapter II of the ICMR Ethical Guidelines for
Biomedical Research on Human Participants that all proposals on biomedical
research in IIT Madras involving human participants should be cleared by an
appropriate the Institutional Ethics Committee, in this case, the IEC - IITM to
safeguard the welfare and the rights of the participants. The IEC is 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.
The basic responsibility of the IEC is to ensure a competent review of all
ethical aspects of the project proposals received by it in an objective manner. IEC
will 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 Technical Review Committee.

The major aspects that IITM-IEC focusses on are as follows:

1. To protect the dignity, rights and well-being of the potential research
participants.
2. To ensure that universal ethical values and international scientific standards are
expressed in terms of local community values and customs.
3. To assist in the development and the education of a research community
responsive to local health care requirements
.
TERMS OF REFERENCE
The Terms of References should include Terms of Appointment with
reference to the duration of the term, the policy for removal, replacement,
resignation procedure, frequency of meetings, and payment of processing fee to the
IEC for review, honorarium / consultancy to the members/ invited experts etc. and
these should be specified in the SOP which should be made available to each
member. Every IEC should have its own written SOPs according to which the
Committee should function.

The SOPs should be updated periodically based on the changing requirements. The
term of appointment of members could be extended for another term and a defined
percentage of members could be changed on regular basis. It would be preferable
to appoint persons trained in bioethics or persons conversant with ethical
guidelines and laws of the country. Substitute member may be nominated if
meetings have been continuously missed by a member due to illness or other
unforeseen circumstances. For this the criteria for number of missed meetings may
be defined in the SOP.

TRAINING
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 responsibilities. 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

REGULATION
Once the legislation of guidelines occurs which is currently under active
consideration by the Ministry of Health, a Biomedical Research Authority will be
set up under the proposed Bill on Biomedical Research on Human

Participants(Promotion and Regulation) which would require that all IECs register
with this Authority. It will also evaluate and monitor functioning of the IECs, and
develop mechanisms for enforcing accountability and transparency by the
institutions.

REVIEW PROCEDURES
The IEC should review every research proposal on human participants
before the research is initiated. It should ensure that a scientific evaluation has
been completed before ethical review is taken up. The Committee should evaluate
the possible risks to the participants with proper justification, the expected benefits
and adequacy of documentation for ensuring privacy, confidentiality and the justice
issues.
The IECs member-secretary or secretariat shall screen the proposals for their
completeness and depending on the risk involved categorise them into three types,
namely, exemption from review, expedited review and full review (see below for
explanation). Minimal risk would be defined as one which may be anticipated as
harm or discomfort not greater than that encountered in routine daily life activities
of general population or during the performance of routine physical or
psychological examinations or tests. However, in some cases like surgery,
chemotherapy or radiation therapy, great risk would be inherent in the treatment
itself, but this may be within the range of minimal risk for the research participant
undergoing these interventions since it would be undertaken as part of current
everyday life. An investigator cannot decide that her/his protocol falls in the
exempted category without approval from the IEC. All proposals will be

scrutinized to decide under which of the following three categories it will be

considered:

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
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 c.),

intended intervention, dosages of drugs, route of

administration, duration of treatment and details of invasive procedures if any.

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.
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.
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.
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.(Format for JNU
provided)

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

DECISION MAKING PROCESS

The IEC should be able to provide complete and adequate review of the
research proposals submitted to them. It should meet periodically at frequent
intervals to review new proposals, evaluate annual progress of ongoing ones,
review serious adverse event (SAE) reports and assess final reports of all research
activities involving human beings through a previously scheduled agenda,
amended wherever appropriate. The following points should be considered while
doing so:
1. The decision must be taken by a broad consensus after the quorum requirements
are fulfilled to recommend / reject / suggest modification for a repeat review or
advice appropriate steps. The Member Secretary should communicate the decision
in writing to the PI.
2. If a member has conflict-of-interest (COI) involving a project then s/he should
submit this in writing to the chairperson before the review meeting, and it should
also be recorded in the minutes.,
3. If one of the members has her/his own proposal for review or has any COI then
s/he should withdraw from the IEC while the project is being discussed
4. A negative decision should always be supported by clearly defined reason

5. An IEC may decide to reverse its positive decision on a study if it receives

information that may adversely affect the risk/ benefit ratio.
6. The discontinuation of a trial should be ordered if the IEC finds that the goals of
the trial have already been achieved midway or unequivocal results are obtained.
7. In case of premature termination of study, notification should include the
reasons for termination along with the summary of results conducted till date.
8. The following circumstances require the matter to be brought to the attention of
IEC:
a. any amendment to the protocol from the originally approved protocol with
proper justification;
b. serious and unexpected adverse events and remedial steps taken to tackle
them;
c. any new information that may influence the conduct of the study.
9. If necessary, the applicant/investigator may be invited to present the protocol or
offer clarifications in the meeting. Representative of the patient groups or interest
groups can be invited during deliberations to offer their viewpoint.
10. Subject experts may be invited to offer their views, but should not take part in
the decision making process. However, her / his opinion must be recorded.
11. Meetings are to be minuted which should be approved and signed by the
Chairperson/ alternate Chairperson/ designated member of the committee.

REVIEW PROCESS
The method of review should be stated in the SOP whether the review
should be done by all reviewers or by primary reviewer(s) in which case a brief
summary of the project with informed consent and patient information sheet,
advertisements or brochures, if any, should be circulated to all the other members.
The ethical review should be done in formal meetings and EC should not take
decisions through circulation of proposals. The committee should meet at regular
intervals and should not keep a decision pending for more than 3 - 6 months, which
may be defined in the SOP.
PERIODIC REVIEW
The ongoing research may be reviewed at regular intervals of six months to one
year as may be specified in the SOP of the ethics committee.

CONTINUING REVIEW
The IEC has the responsibility to continue reviewing approved projects for
continuation, new information, adverse event monitoring, follow-up and later after
completion if need be.
INTERIM REVIEW

Each IEC should decide the special circumstances and the mechanism when an
interim review can be resorted to by a sub-committee instead of waiting for the
scheduled time of the meeting like re-examination of a proposal already examined
by the IEC or any other matter which should be brought to the attention of the IEC.
However, decisions taken should be brought to the notice of the main committee.

MONITORING
Once IEC gives a certificate of approval it is the duty of the IEC to monitor the
approved studies, therefore an oversight mechanism should be in place. Actual site
visits can be made especially in the event of reporting of adverse events or
violations of human rights. Additionally, periodic status reports must be asked for
at appropriate intervals based on the safety concerns and this should be specified in
the SOP of the IEC. SAE reports from the site as well as other sites are reviewed
by EC and appropriate action taken when required. In case the IEC desires so,
reports of monitoring done by the sponsor and the recommendations of the DSMB
may also be sought.

RECORD KEEPING
All documentation and communication of an IEC are to be dated, filed and
preserved according to written procedures. Strict confidentiality is to be maintained
during access and retrieval procedures. The following records should be
maintained for the following:
i. The Constitution and composition of the IEC;

ii. Signed and dated copies of the latest the curriculum vitae of all IEC members
with records of training if any;
iii. Standing operating procedures of the IEC;
iv. National and International guidelines;
v. Copies of protocols submitted for review;
vi. All correspondence with IEC members and investigators regarding application,
decision and follow up;
vii. Agenda of all IEC meetings;
viii. Minutes of all IEC meetings with signature of the Chairperson;
ix. Copies of decisions communicated to the applicants;
x. Record of all notification issued for premature termination of a study with a
summary of the reasons;
xi. Final report of the study including microfilms, CDs and Video recordings.
It is recommended that all records must be safely maintained after the
completion/termination of the study for a period of 3 years if it is not possible to

maintain the same for more than that due to resource crunch and lack of
infrastructure.

Documentation
For a thorough and complete review, all research proposals should be
submitted
with the following documents :
1.Name of the applicant with designation.
2.Name of the Institute/ Hospital / Field area where research will be conducted
3. Approval of the Head of the Department / Institution

4.Protocol of the proposed research

5. Ethical issues in the study and plans to address these issues.

6. Proposal should be submitted with all relevant enclosures like proformae, case
report forms, questionnaires, follow - up cards, etc.
7. Informed consent process, including patient information sheet and informed
consent form in local language(s).
8. For any drug / device trial, all relevant pre-clinical animal data and clinical

trial data from other centres within the country / countries, if available.
9. Curriculum vitae of all the investigators with relevant publications in last five
years.
10. Any regulatory clearances required.
11. Source of funding and financial requirements for the project
.
12. Other financial issues including those related to insurance
13. An agreement to report only Serious Adverse Events (SAE) to IEC.
14. Statement of conflicts of interest, if any.
15. Agreement to comply with the relevant national and applicable international
guidelines.
16. A statement describing any compensation for study participation (including
expenses and access to medical care) to be given to research participants; a
description of the arrangements for indemnity, if applicable (in study-related
injuries); a description of the arrangements for insurance coverage for
research participants, if applicable; all significant previous decisions(e.g.,
those leading to a negative decision or modified protocol) by other ECs or
regulatory authorities for the proposed study (whether in the same location or
elsewhere) and an indication of the modification(s) to the protocol made on

that account. The reasons for negative decisions should be provided.

17. Plans for publication of results positive or negative- while maintaining the
privacy and confidentiality of the study participants.
18. Any other information relevant to the study

Essential Clinical Trial EC Review Topics

Several important ethical issues have to be correctly addressed for EC

approval, including the risk-benefit balance, vulnerable participants, sensitive
privacy concerns contents of informed consent, advertising for recruitment of
participants, the investigators qualifications, conflicts of interest and tissue/blood
sampling. Each EC has its own operational framework, while views on ethical
matters vary among EC members and different ECs.
Both the Declaration of Helsinki and the ICH GCP Guideline clearly define
aspects of the

scientific requirements of a clinical trial. For instance, medical

research involving

participants must conform to generally accepted scientific

principles, conducted in an adequate laboratory, and be based on thorough

knowledge of the scientific literature and other relevant sources of information
including, when appropriate, animal experimentation. Clinical trials should be
described in a clear, detailed protocol. When an EC reviews a trial protocol, it
should discuss the scientific soundness of the protocol. To enable an informed,
detailed discussion, EC members must be able to understand the scientific and

clinical rationale behind the protocol. This is why EC members should be provided
with a detailed trial protocol. A protocol that is unsound from either a scientific
and/or clinical viewpoint should not be conducted and thus not be approved by
the EC.
A clinical trial that will not advance knowledge about a certain medical test
article should not be conducted, since the risk-benefit balance for participants will
be unacceptably high. With any trial there comes a certain risk of harm e.g.,
expected adverse events ranging from accidents when traveling to the study site,
to catching an infectious disease in a health care setting or encountering an adverse
event during a routine practice that is an unnecessary, rather than standard,
treatment-related medical procedure. But even if the results are negative
ultimately showing no beneficial effect of the test article the trial still advances
our knowledge. All data collected during a clinical trial must be free of errors. It is
intended for use as an important body of evidence when a new medicinal product
is reviewed by the government drug regulatory authority. Before a product can be
used in medical care ,the regulatory authority reviews the results from all trials of
the product. After approval is granted, the product will be given to a large patient
population. For this reason, the regulatory authority must be sure that all
supporting data included in the new drug application file are trustworthy and
reliable, so the efficacy and safety profile of the product can be accurately
established. This is why quality assurance is an important issue in clinical trials

Issues of EC Procedures

Local Laws and Institutional Guideline

International human protection research guidelines, such as the Declaration of
Helsinki and the ICH GCP Guideline, unfold the basic concepts and principles of
research ethics of clinical trials. However, the interpretation and implementation of
those and other guidelines are highly dependent on local laws and guidance. The
EC and its members must therefore be well-versed and know the applicable local
laws and guidance
All human research projects must be reviewed sufficiently, but ethics review
should be proportionate to the level and nature of the risks. A balanced ethics
review approach starts with assessment of the risk of harm and potential benefits
associated with the research (see
illustration).The concept of minimal risk provides the foundation for a balanced
review, and in deciding whether a full board review,conducted by the convened
EC, or an expedited review using expedited procedures should be adopted. A
minimal risk situation is where the probability and magnitude of harm or
discomfort anticipated in the research are not greater than those ordinarily
encountered in daily life or during the performance of routine physical or
psychological examinations or tests.
The decision to conduct an expedited review may be made by the chair of the EC.
The chair is required to adopt a method of keeping all members advised of research
studies that have been approved by expedited review. Virtually all clinical trials are
at least initially subject to a full EC review, and usually the continuing review of
trials must be conducted by the full EC. Views differ among ECs whether, for
instance, scheduled continuing reviews, safety reports or protocol amendments are

acceptable for expedited review or not, and this is driven by local laws and
institutional guidelines.

Acceptability of Trial
The EC should deem that all clinical trials are subject to scientific review, and thus
avoid putting participants at unnecessary risk of harm. A scientific review judges
the importance of the research question and validity of the methodology; this can
only be assessed by those familiar with the disciplines and methods of the
proposed research. Traditionally, clinical trials undergo scientific review as part of
the EC review process, using appropriate expertise among EC members. Clinical
trials overseen by regulatory authorities will have already been subject to scientific
review prior to the EC review. It is thus good practice to collect information from
the EC application about the types of scientific reviews a particular trial has been
subject to prior to the EC review, for instance, by regulatory authorities or granting
agencies. Any protocol raising many minor concerns or a few major concerns
should either be rejected or subject to revision and subsequently re-assessed.
Results from a trial not based on or adhering to current scientific knowledge,
lacking important pre-clinical information and/or using substandard trial design
will, in most cases, not be conclusive and therefore not be useful. Such trials could
also put participants at risk of harm without any scientific reason, while also
consuming financial and human resources that might be more purposefully
directed to other more important research projects.

ABBREVIATIONS

ADR

Adverse Drug Reaction

AE

Adverse Event

CRA

Clinical Research Associate

CRC

Clinical Research Coordinator

CRFs
CRO

Case Report Forms

Clinical Research Organisation

DSMC

Data Safety and Monitoring Committee

EC

Ethics Committee

EMEA

European Medicines Agency

ERB

Ethics Review Board

FDA

Food and Drug Administration

GCP

Good Clinical Practice

GLP

Good Laboratory Practice

GMP

Good Manufacturing Practice

HRPP

Human Research Protection Programmes

ICH

International Conference on Harmonisation

ICMJE

International Committee of Medical Journal

IDMC

Independent Data Monitoring Committee

IEC

Independent Ethics Committee

IND

Investigational New Drug Application

IRB

Institutional Review Board

NDA

New Drug Application

QoL

Quality of Life

REC

Research Ethics Committee

SAE

Serious Adverse Event

SOPs

Standard Operating Procedures

WMA

World Medical Association

Conclusion
In summary, research is commonplace in short-term training programs in
global health. This is true in medicine, public health, engineering, and many other
disciplines.

By exploring this case, we have learned several important lessons regarding

the ethical issues arising when trainees in short-term training programs conduct
research.
1. Collaboration in advance of the research can help ensure it is scientifically
valid, responsive to local needs, and ethically designed and conducted.
Many times, research needs many months of advanced preparation for a
successful collaboration.

2. This case involved several potentially competing aims: Bryces career goals,
the interests of his home advisor, the sponsors funding choice, and the local
priorities. In general, local priorities should take priority when designing a
research project.

3. Lastly, trainees, sending and host institutions, and sponsors should all be
aware that research is subject to IRB and local ethics committee oversight.
When questions arise or changes to the research occur, it is imperative to
contact these oversight bodies for advice and approval.