IRB - ICF - PROTOCOL

INSTITUTIONAL REVIEW
BOARD
Dr. Suman Baishnab

INTRODUCTION
 Experimentation on human being is subject to ethical
standards that promote respect for all and protect
their health and rights
Research requiring ethical review:
 Research involving living human subjects and use of
their medical records
 Research involving human remains, cadavers,
biological fluids, tissues, embryos, fetuses and etc.

INTRODUCTION…
 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

CONSTITUTION OF IRB
 The IRB should consist atleast SEVEN members, who
collectively have the qualifications and experience to
review and evaluate the science, medical aspects,
and ethics of the proposed trial. viz.
1. Chairperson – Appointed (who is from outside the
institution)
2. 1-2 basic medical scientists
3. 1-2 clinicians from various institutes
4. One legal expert or retired judge
5. One social scientist
6. One philosopher or ethicist
7. One lay person from community
8. Member secretary – Appointed

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 or
a similar person
5. Lay person from the community

QUORUM OF IRB…
In any case, the IRB must include
 at least one member whose primary area of
interest / specialization is nonscientific
 at least one member who is independent of the
institution / trial site
Besides, there should be appropriate gender
representation on the IRB
If required, Subject experts may be invited to offer
their views
Further, based on the requirement of research area,
e.g. AIDS, genetic disorders etc. specific patient groups
may also be represented in the IRB

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/or
advise
The IRB should perform its functions according to
written standard operating procedures, should maintain
written records of its activities and minutes of its
meetings, and should comply with GCP and with the
applicable regulatory requirement(s)

IRB…
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
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
appropriate

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
change(s) involves only logistical or administrative
aspects of the trial

IRB…
Specifying that the investigator should promptly report
to the IRB
Deviations from, or changes of, the protocol to
eliminate immediate hazards to the trial subjects
Changes increasing the risk to subjects and/or
affecting significantly the conduct of the trial
All adverse drug reactions (ADRs) that are both serious
and unexpected
New information that may affect adversely the safety
of the subjects or the conduct of the trial

IRB…
Ensuring that the IRB promptly notify in writing the
investigator/institution concerning
Its trial-related decisions/opinions
The reasons for its decisions/opinions
Procedures for appeal of its decisions/opinions

RESPONSIBILITIES OF IRB
An IRB should safeguard the rights, safety, and well-
being of all trial subjects
The IRB should obtain the following documents
Trial protocol(s)/amendment(s)
Written informed consent form(s)
Subject recruitment procedures (e.g.: Advertise)
Written information to be provided to subjects
Investigator’s Brochure (IB)
Available safety information
Information about payments and compensation
Investigator’s current curriculum vitae
Any other may need to fulfill its responsibilities

RESPONSIBILITIES OF IRB…
The IRB should review a proposed clinical trial within a
reasonable time and document its views in writing,
clearly identifying the trial, the documents reviewed
and the dates for the following
Approval / favourable opinion
modifications required prior to its approval /
favourable opinion;
disapproval / negative opinion
Termination / suspension of any prior approval /
favourable opinion
The IRB should consider the qualifications of the
investigator for the proposed trial, as documented by a
current curriculum vitae and / or by any other relevant
documentation the IRB requests

The IRB/IEC should conduct 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

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 subjects, including the methods, amounts,
and schedule of payment to trial subjects, is set forth in
the written informed consent form and any other
written information to be provided to subjects

IRB / IEC ?????
US FDA – use the term IRB
EMEA – use the term IEC
ICH-GCP: use the term IRB/IEC
Canada: use the term REC (Research Ethics
Committee)
IRB stands for ‘Institutional Review Board”
IEC stands for ‘Independent Ethics Committee’
IEC are generally established in regional or even
national level – can review protocol from anyone
IRB are generally established by an organization – will
review protocols of that institution / organization
Indian guidelines were developed mostly based on
ICH-GCP guidelines

INFORMED CONSENT FORM
A major component of GCP is the method by which the
researchers 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 subject population in
terms that they can understand

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 Subject's participation
Description of the procedures to be followed, including
all invasive procedures and
Description of any reasonably foreseeable risks or
discomforts to the Subject
Description of any benefits to the Subject or others
reasonably expected from research. If no benefit is
expected Subject should be made aware of this.

6.Disclosure of specific appropriate alternative
procedures or therapies available to the Subject
7.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
8.Trial treatment schedule(s) and the probability for
random assignment to each treatment (for randomized
trials)
9.Compensation and/or treatment(s) available to the
Subject in the event of a trial related injury

10. An explanation about whom to contact for trial
related queries, rights of Subjects and in the event of
any injury
11.The anticipated prorated payment, if any, to the
Subject for participating in the trial
12.Subject's responsibilities on participation in the trial
13.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

Any other pertinent information which may be
required, viz.
a.Statement of foreseeable circumstances under which
the subject's 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 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), which are currently unforeseeable
f.Approximate number of Subjects enrolled in the study

FORMAT OF INFORMED CONSENT
FORM
Informed Consent Form To Participate In A Clinical Trial
Study Title:
Study Number:
Subject's Initials: _____________
Subject's Name:_______________
Date of Birth / Age: _________________
Please initial
box (Subject)

FORM…
Please initial in boxes:
1.I am above 18 years old [ ]
2.I confirm that I have read and understood the
information sheet dated ___ for the above study and
have had the opportunity to ask questions [ ]
3.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 [ ]
4.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) [ ]

FORM…
Please initial in boxes:
………………………..
……………………
5.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: __/__/__

FORM…
Study Investigator's Name:_______________
Signature of the Witness________ Date:__ /__ /__
Name of the Witness:_______________________

CONTENTS OF THE PROTOCOL
Title Page
a. Full title of the clinical study
b. Protocol / Study number, and protocol version
number with date
c. The IND name / number of the investigational
drug / Drug Name
d. Complete name and address of the Sponsor and
contract research organization if any / Investigator
e. List of the Investigators who are conducting the
study, their respective institutional affiliations and site
locations
f. Name(s) of clinical laboratories and other
departments and/or facilities participating in the study

CONTENTS OF THE PROTOCOL
Table of Contents
A complete Table of Contents including all Appendices
1. Background and Introduction:
a. Preclinical experience
b. Clinical experience
2. Study Rationale
3. Study Objective(s) (primary as well as secondary)
4. Study Design
a. Overview of the Study Design: (i.e., double blind,
multicenter, placebo controlled, etc.), a detail of the specific
treatment groups and number of study Subjects in each
group and investigative site, Subject number assignment,
and the type, sequence and duration of study periods

CONTENTS OF THE PROTOCOL…
b. Flow chart of the study
c. A brief description of the methods and procedures
to be used during the study
d. Discussion of Study Design: This discussion details
the rationale for the design chosen for this study
5. Study Population
6. Subject Eligibility
a. Inclusion Criteria
b. Exclusion Criteria
7. Study Assessments plan, procedures and methods
Medical history, Types of physical examination, Blood or
Urine testing, ECG, PFT, symptom measurement,
Dispensation and Retrieval of medication, Subject cohort
assignment, adverse event review, etc.

Each visit should be described separately as Visit 1, Visit 2,
etc.
Discontinued Subjects: Describes the circumstances for
Subject withdrawal, dropouts, or other reasons for
discontinuation of subjects and how drop outs would be
managed and if they would be replaced should be stated
Describe the method of handling of protocol waivers, if any
The person(s) who approves all such waivers should be
identified and the criteria used for specific waivers should be
provided
Describes how protocol violations will be treated, including
conditions where the study will be terminated for non-
compliance with the protocol

8. Study Treatment
a. Dosing schedule ( dose, frequency, and duration of
the experimental treatment, Placebos and/or
dummy)
b. Study drug supplies and administration:
c. Dose modification for study drug toxicity:
d. Possible drug interactions
e. Concomitant therapy
f. Blinding procedures
g. Unblinding procedures
9. Adverse Events (Description of expected adverse events
should be given and procedures used to evaluate an adverse event
should be described)

10. Ethical Considerations: Give the summary of:
a. Risk/benefit assessment
b. IRB review and communications
c. Informed consent process
d. Statement of subject confidentiality
11. Study Monitoring and Supervision
 A description of study monitoring policies and
procedures along with the proposed frequency of site
monitoring visits, and who is expected to perform
monitoring
 Case Record Form (CRF) completion requirements, CRF
correction requirements, including who is authorized to
make corrections on the CRF and how queries about
study data are handled and how errors, if any, are to
be corrected

 Investigator study files, including what needs to be
stored following study completion should be described
12. Investigational Product Management
a. Give Investigational product / placebo description
and packaging
b. The precise dosing required during the study
c. Method of packaging, labeling, and blinding of
study substances
d. Method of assigning treatments to subjects and the
subject identification code numbering system
e. Storage conditions for study substances
f. Investigational product accountability
g. Describe policy and procedure for handling unused
investigational products

13. Data Analysis
Details of the statistical approach to be followed including
sample size
Efficacy endpoints (primary as well as secondary)
Safety endpoints
Statistical analysis (techniques, level of significance,
statistical tests to be used)
Methods used for missing data
Method of evaluation of the data for treatment failures
Noncompliance
Subject withdrawals, rationale and conditions for any
interim analysis if planned
Statistical considerations for Pharmacokinetic (PK) analysis,
if applicable

14. Undertaking by the Investigator
As described in the regulatory guidelines
15. Appendices:
Study synopsis
Copies of the informed consent documents with patient
information sheet
CRF and other data collection forms
Summary of relevant pre-clinical safety information and any
other documents referenced in the clinical protocol

IRB - ICF - PROTOCOL

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