GCP and EC Training (2).ppt

Institutional Ethics committee
Training
On
GCP & Schedule Y

BASICS OF CLINICAL RESEARCH
REGULATORY OVERVIEW
INTRODUCTION TO GCP
INTRODUCTION TO SCHEDULE Y
INSTITUTIONAL ETHICS COMMITTEE

Clinical research
Organized research on human beings
A systematic study of new drug(s) in
human subject(s) to generate data for
discovering and verifying the clinical,
pharmacological and adverse effects
with the objective of determining
safety and efficacy of the new drug

Phases of Clinical Trials
Phase I - Is the treatment safe?
Human Pharmacology
Phase II - Does the treatment work?
Therapeutic Exploratory
Phase III - Does the new treatment
work better than the standard treatment?
Therapeutic Confirmatory
Phase IV - Is the treatment safe over
time?
Therapeutic Use

Drug development at
large discovery to clinical
usage over an average of
12 to 15 years

Declaration of Helsinki – 1964 -
by WMA
WHO and ICH Guidelines for
Good Clinical Practice. -1996
- by EU, US and Japan (E6
GCP - Globally accepted
guideline for conducting
clinical research)
ICMR – Ethical guidelines
for biomedical research
on human participants.
 Indian GCP Guidelines
 Schedule Y
(Law for clinical
Research In India)
 Drug Controller General of
India – Regulatory Authority
of India
Global Guidelines National Guidelines
The ethical and scientific standards for carrying out biomedical research
on human subjects have been developed and established in
guidelines, including

 Nazis war medical experiments in 1945
during second world war
Injecting people with gasoline and live viruses
 Immersing people in ice water
 Forcing people to ingest poisons
Thalidomide disaster in 1950 – 1960
 Thalidomide was a widely used drug in treatment of
nausea in pregnant women
 It became apparent in the 1960s that thalidomide
treatment resulted in severe birth defects in thousands
of children leading to the ban of thalidomide in most
countries in 1961
HISTORICAL
OVERVIEW
TheTuskegee Syphilis Study
 Almost 400 Black males with syphilis recruited with out consent to study
the natural history of untreated syphilis
The Will Brook Study
In order to gain an understanding of the natural history of infectious
hepatitis under controlled circumstances, newly admitted children were
deliberately infected with the hepatitis virus

 Nuremberg Code (1947).
 W.M.A’s Declaration of Helsinki (1964).
 Belmont Report (USA) (1979)
 Council for International Organizations of
Medical Sciences (CIOMS) 1993.
 International Conference on Harmonization of
Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH), in 1996,
Guideline on Good Clinical Practice,E6 (GCP).
Evolution of ICH GCP
HISTORICAL
OVERVIEW

of technical requirements for
registrations of pharmaceuticals for
human use
ICH Overview

Idea of ICH Established in 1989
First Steering Group Meeting in July 1990
6 Principal Participants: Regulatory Agencies &
Pharmaceutical Manufacturers
Observers: World Health Organization, Australia, Canada,
European Free Trade Association (EFTA)
ICH – History & Participants

• Efficacy:
– Clinical trials ( E6 Stands for GCP Guidelines)
• Safety:
– Pharmacovigilance, adverse drug reaction reporting
• Quality:
– Raw materials, impurities, residual solvents etc
• Multidisciplinary:
– Common technical document, electronic submission,
coding systems
ICH Guidelines

A standard for the design, conduct,
performance, monitoring, auditing,
recording, analyses and reporting
of clinical trials that provides
assurance that the data and
reported results are credible and
accurate, and that the rights,
integrity and confidentiality of the
subjects are protected.
ICH Definition of GCP

• Ensure rights of
subjects
• Ensure quality,
efficacy, safety
• Eliminate delays in
the development
and availability of
new drugs
Good Clinical Practice
(GCP)
GCP Objectives
• Poor quality data
• Subject safety at
risk
• Study data rejected
by competent
authorities
GCP Non-
compliance
results in...

The Principles of ICH GCP
2.1 Clinical trials should be conducted in accordance with the ethical
principles that have their origin in the Declaration of Helsinki, and
that are consistent with GCP and the applicable regulatory
requirement(s)
2.2 Before a trial is initiated, foreseeable risks and inconveniences
should be weighed against the anticipated benefit for the individual
trial subject and society. A trial should be initiated and continued only
if the anticipated benefits justify the risks.
2.3 The rights, safety, and well-being of the trial subjects
are the most important considerations and should prevail over
interests of science and society.
2.4 The available nonclinical and clinical information on
an investigational product should be adequate to support the
proposed clinical trial.
2.5 Clinical trials should be scientifically sound, and
described in a clear, detailed protocol.

2.6 A trial should be conducted in compliance with the protocol
that has received prior institutional review board
(IRB)/independent ethics committee (IEC) approval/favourable
opinion.
2.7 The medical care given to, and medical decisions made
on behalf of, subjects should always be the responsibility of a
qualified physician or, when appropriate, of a qualified dentist
2.8 Each individual involved in conducting a trial should be qualified
by education, training, and experience to perform his or her
respective task(s).
2.9 Freely given informed consent should be obtained from
every subject prior to clinical trial participation.
2.10 All clinical trial information should be recorded,
handled, and stored in a way that allows its accurate reporting,
interpretation and verification.

2.11 The confidentiality of records that could
identify subjects should be protected,
respecting the privacy and confidentiality rules in
accordance with the applicable regulatory requirement(s)
2.12 Investigational products should be
manufactured, handled, and stored in
accordance with applicable good
manufacturing practice (GMP). They should
be used in accordance with the approved
protocol.
2.13 Systems with procedures that assure the
quality of every aspect of the trial should be
implemented.”

Parties Involved in Clinical
Trial Conduct

S
U
B J E
C
T
S
Who are Involved in Clinical Trials?

Reviewing and approving clinical trial
protocols.
Ensuring that clinical trials comply with
national regulations of a country and
international guidelines.
 Make sure the compensation will be
paid to the subjects
Responsibilities of the regulatory authority

Who is Sponsor?
An individual, company, institution, or
organisation which takes responsibility
for the initiation, management, and/or
financing of a clinical trial

Sponsor Responsibilities
• Quality Assurance and Quality Control
• Trial Management, Data Handling, and Record
Keeping
• CRO selection
• Investigator Selection
• Compensation to Subjects and Investigators
• Financing
• Notification/Submission to Regulatory
Authority(ies)

Sponsor Responsibilities
• Manufacturing, Packaging, Labelling, and
Coding Investigational Product(s)
• Supplying and Handling Investigational
Product(s)
• Monitoring
• Audit
• Clinical Trial/Study Reports

ICH GCP - Investigator Obligations

 Protecting the rights and well-being of the
participants.
 Following GCP and other guidelines.
 Having access to all necessary facilities.
 Following the protocol.
 Ensuring the clinical trial is reviewed by an EC.
 Informing the EC of any adverse events.
 Ensuring an ongoing informed consent process
for the participants.
 Protecting participants’ identity.
 Proper handling of all trial medications/supplies.
 Reviewing and reporting adverse events during
the trial.
Responsibilities of The Investigator

PROTOCOL
 Document that describes objective, design,
methodology, statistical considerations , back
ground, rationale and organization of the
study
INVESTIGATIONAL BROCHURE
 A compilation of clinical and non clinical
data on Investigational product
ESSENTIAL DOCUMENTS
 Documents individually and collectively
evaluation of conduct of study

The main regulatory law operating in India is Drug and
cosmetic Act (1940) and Drug and cosmetic act rules(1945)
Drug regulatory process come under Drug Controller
General of India who is the head of Central Drug Standard
Control Organization
Schedule Y
Requirements of guideline for permission to
import and manufacture new drugs for sale or to
undertake clinical trials

SUMMARY OF SCHEDULE Y
1.Application for permission
2.Clinical Trial
Approval for clinical trials
Responsibilities of sponsor
Responsibilities of Investigator
Informed Consent
Responsibility of Ethics Committee
Phases of Clinical trials
3. Studies in Special Population –
Geriatrics, Paediatrics, Pregnant Woman
4. Special studies BA/BE
5. 11 Appendices

INSTITUTIONAL ETHICS
COMMITTEE

Definition
 Independent body constituted 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
by, among other things, reviewing, approving &
providing continuing review of trial protocol &
amendments.

Structure of IEC
The IRB/IEC should consist of a reasonable
number of members, who collectively have
the qualifications and experience to review
and evaluate the science, medial aspects
and ethics of the proposed trial.
Composition:
• Multidisciplinary and multisectorial in
composition
• Number of persons minimum 7 maximum 15

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
Other members should be a mix of medical/non-
medical, scientific & non-scientific persons,
including lay public to reflect the different
viewpoints

Roles and
Responsibilities of
Ethics Committee

Responsibilities of the EC :
Safeguard the rights, safety and well-being of all
trial participants; special attention should be
paid to trials that may include vulnerable
participants.
Review the protocol and associated documents and
provide opinions within a reasonable time,
documenting its views in writing in a timely manner.
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 EC requests.

Conduct continuing review of each
ongoing trial at intervals appropriate to
the degree of risk to human participants,
but at least once a year.
 Reviewing certain types of adverse
events and any harm that happens as a
result of the trial.
Responsibilities of the EC

Quorum requirement
For review of each protocol the quorum of Ethics
Committee should be at least 5 members with
the following representations:
(a) basic medical scientists (preferably one
pharmacologist).
(b) clinicians
(c) legal expert
(d) social scientist / representative of non-
governmental voluntary agency /philosopher / ethicist
/ theologian or a similar person
(e) lay person from the community.

What does an EC do?
Before the study begins:
• Collecting the essential/ study related
documents
• Review of proposal
• Decision making process
1. approval/ favorable opinion;
2. modifications required prior to its approval/
favorable opinion;
3. termination/suspension of any prior approval/
favorable opinion.

During the study:
 Review of amendments ( Protocol, ICD)
 Review of Serious Adverse Events
 Protocol deviations
 Monitoring the study status , collecting study
progress report from site
 Record keeping
What does an EC do?

After the study:
 Final Study report
 Post trial management
 Record keeping
What does an EC do?

Overall Responsibility
 Before start of research
Review
Approval
 While research is in progress
Monitor
 After completion of research
Archiving
NO clinical trial should be initiated at
any investigator site without a written
approval from the respective EC

• Study Protocol
• Translations of ICD in vernacular language
• IB
• Investigator CV
• Undertaking by the investigator
• Insurance
• Subject recruitment procedures
• Regulatory approval for the trial/ Submission status
• Insurance Policy / Compensation for participation and for
unexpected serious adverse events occurring during the study
participation.
• Any other written information to be provided to the subjects
Documents to be submitted to ethics
committee by investigator

How to perform an Ethical Review?
I. Scientific design and conduct of study
II. Recruitment of Research Participants
III. Care and Protection of Research Participants
IV. Protection of research participant
confidentiality
V. Informed Consent Process
Points to be considered

I. Scientific Design and Conduct of Study
 Appropriateness of study design
 Statistical methodology including sample size
calculation
 Risk v/s 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

II. 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

III. 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
 Insurance and indemnity arrangements

IV. 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.

V. 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.
 To Ensure Audio Video recording is followed
for Vulnerable subjects

Basic Documents of
Ethics Committee

 EC Registration Letter from DCGI
 National and International Guidelines
Standard Operating Procedure
1.Introduction
2.Responsibilities of IEC
3.Composition and Membership requirements of Ethics
Committee
4.Independent consultants
5.Quorum Requirements
6.Authority and Administrative office of IEC
Basic Documents of Ethics Committee

7. Meeting Procedures
8. Minimum required documents for submission of
research project for approval.
9. Element of review
10.Decision-making
11.Communicating the decision
12.Follow up review procedures
13.Expedited / Interim review
14.Archiving/Record keeping
15.Training and Updating IEC members
16.The committee expects from the investigators

 EC Membership list
 CV of EC Members
 Consent to be member of EC
 Confidentiality Agreement of Members
 Training Records
 Copy of documents submitted to DCGI for Registration
 Agenda and EC Meeting Minutes approved by
Chairperson
 EC Meeting Attendee List
 All correspondence with IEC members and Investigators
regarding application, decision and follow up.

 Copies of Documents submitted for review
 Submission letters of the studies
 Copies of decisions communicated to applicants
 EC Notification letters
 Notifications issued for premature termination of
study
 Progress/ status reports of every studies
 Close out report, Final Report and CSR Report
 Letters of communication with DCGI

Meeting Procedures of EC
 Meeting Frequency as per SOP
 Member Secretary is the coordinating person
 Study documents must be submitted/Collected
as per the SOP before the meeting
 Acknowledgment Must be given before the
meeting.

 Invitation for the Meeting
 Agenda for the Meeting
 Distribution of study dossiers to all
members in the EC
Before the meeting :
During the meeting:
 Ensure the quorum requirement
 Attendance of all the members
attending
 Investigator presents the study
proposal
 Discussion
 Voting for the study
 Record Minutes of meeting
After the Meeting :
 Issue of Approval/ Query letter
 Minutes of meeting prepared by
Member Secretary
 Minutes of meeting approval by
chairperson
Meeting Procedures of EC

EC Registration
and
Renewal Procedures

 Gazette Notification GSR 72 (E) Effective
08th Feb 2013
 Documents to be submitted as per check list
issued by DCGI
 EC registration should renew every 3 years
 EC has to update in writing in case of
change in EC Members
EC Registration and Renewal Procedures

Audit can occur from Regulatory Authorities
to Ensure the following:
 Verification of Name and Address of EC with
various documents
 All EC documents are up to date
 Functioning of EC according to SOP
 SAE analyzed report and recommendation for
compensation and other notifications to the
Regulatory on timely manner
 All the studies are properly reviewed and Approved
 Verification of persisting review of study progress
 Safety and well being of study subjects by EC

 The IRB/IEC should retain all relevant records (e.g.,
written procedures, membership lists, lists of
occupations/affiliations of members, submitted
documents, minutes of meetings, and
correspondence) for a period of at least 5 years in
India after completion of the trial and make them
available upon request from the regulatory
authority(ies).
 The IRB/IEC may be asked by investigators,
sponsors or regulatory authorities to provide its
written procedures and membership lists.
Record Keeping

Report To Whom - Regulatory
What to report:
 EC administrative changes
 In case of SAE,
1. EC must get initial report from investigator
with in 24 Hrs
2. EC must get follow report after analysis from
investigator and sponsor with in 14 days
3. EC must send SAE Analyzed report and opinion
about Compensation to DCGI with in 30 days
of the occurrence of the event

Conclusion
An Institutional Ethics Committee is a mandatory
requirement as per the ICMR which is the over –
seeing body of medical research in India
It is an Independent body constituted 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

Regulations
Ethics
Science
Economics
Agreements
Responsibility
Collaboration
Hard work

GCP and EC Training (2).ppt

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