Assignment on Regulatory Prespectives of Clinical Trials

ICH-GCP GUIDELINES
INTRODUCTION:
 Good Clinical Practice (GCP) is an international ethical
and scientific quality standard for designing, conducting,
recording and reporting trials that involve the
participation of human subjects.
 Compliance with this standard provides public assurance
that the rights, safety and well-being of trial subjects are
protected
 Objective: ICH GCP Guideline is to provide a unified
standard for the European Union (EU), Japan and the
United States to facilitate the mutual acceptance of
clinical data by the regulatory authorities

THE PRINCIPLES OF ICH GCP
 Clinical trials should be conducted in accordance
with the ethical principles
 The rights, safety, and well-being of the trial subjects
are the most important considerations
 Clinical trials should be scientifically sound, and
described in a clear, detailed protocol.
 The medical care given to, and medical decisions
made on behalf of, subjects should always be the
responsibility of a qualified physician

INVESTIGATOR
1)Investigator's Qualifications and Agreements
 The investigator should be qualified by
education(biostatisticians, clinical pharmacologists, and
physicians) training, and experience to assume
responsibility for the proper conduct of the trial,
should meet all the qualifications specified by the
applicable regulatory requirement
 The investigator should be aware of, and should
comply with, GCP and the applicable regulatory
requirements

2).Adequate Resources:
 The investigator should have sufficient time to properly
conduct and complete the trial within the agreed trial
period
 The investigator should have available an adequate
number of qualified staff and adequate facilities for the
foreseen duration of the trial to conduct the trial properly
and safely
 The investigator should ensure that all persons assisting
with the trial are adequately informed about the protocol,
the investigational product(s), and their trial-related
duties and functions

3).Medical Care of Trial Subjects:
 A qualified physician (or dentist, when appropriate), who
is an investigator or a sub investigator for the trial
 Investigator/institution should ensure that adequate
medical care is provided to a subject for any adverse
events
 4). Communication with IRB/IEC:
 Before initiating a trial, the investigator/institution
should have written and dated approval from the
IRB/IEC for the trial protocol, written informed consent
form, consent form updates, subject recruitment
procedures

5). Compliance with Protocol:
1) The investigator/institution should conduct the trial in
compliance with the protocol agreed to by the sponsor
and, if required, by the regulatory authorities and which
was given approval/favourable opinion by the IRB/IEC.
The investigator should not implement any deviation
from, or changes of the protocol without agreement by
the sponsor and prior review and documented
approval/favourable opinion from the IRB/IEC of an
amendment, except where necessary to eliminate an
immediate hazard to trial subjects

6.Investigational Product:
 The investigator should ensure that the investigational
products are used only in accordance with the approved
protocol
 The investigational products should be stored as
specified by the sponsor and in accordance with
applicable regulatory requirements.
 7.Randomization Procedures and Unblinding
 The investigator should follow the trial's randomization
procedures, and should ensure that the code is broken
only in accordance with the protocol.

8. Informed Consent of Trial Subjects:written
information to be provided to subjects
9. Records and Reports:
 The investigator should ensure the accuracy,
completeness, legibility, of the data reported to the
sponsor in the CRFs and in all required reports
 Sponsors should have written procedures to assure that
changes or corrections in CRFs made by sponsor's
designatedrepresentativesaredocumented

10.Safety Reporting:
 All serious adverse events (SAEs) should be reported immediately to
the sponsor except for those SAEs that identifies as not needing
immediate reporting
11. Premature Termination or Suspension of a Trial :
If the investigator terminates without prior agreement of the sponsor,
the investigator should inform the institution and should provide the
sponsor and the IRB/IEC a detailed written explanation of the
termination or suspension.
If the sponsor terminates investigator/institution should promptly
inform the IRB/IEC and provide the IRB/IEC a detailed written
explanation of the termination or suspension
If the IRB/IEC terminates or suspends its approval the
investigator/institution should promptly notify the sponsor and
provide the sponsor with a detailed written explanation of the
termination or suspension

 12). Final Report by Investigator:
 Upon completion of the trial investigator/institution
should provide the IRB/IEC with a summary of the
trial’s outcome, and the regulatory authority with
any reports required

sponsor
 A system to manage quality throughout all stages of
the trial process.
 The quality management system should use a risk-
based approach as described below
 Risk Identification:
 Risk Evaluation
 Risk Control
 Risk Communication

1. Quality Assurance and Quality Control:
QUALITTY ASSURANCE: To ensure that the trial is
performed and the data are generated, documented
(recorded), and reported in compliance with Good
Clinical Practice (GCP) and the applicable regulatory
requirement
QUALITY CONTROL: The operational techniques and
activities undertaken within the quality assurance
system to verify that the requirements for quality of
the trial-related activities have been fulfilled.

2. Contract Research Organization:
 A sponsor may transfer any or all of the sponsor's trial-
related duties and functions to a CRO, but the ultimate
responsibility for the quality and integrity of the trial
data always resides with the sponsor
3. Medical Expertise:
The sponsor should designate appropriately qualified
medical personnel who will be readily available to advise
on trial related medical questions or problems
4. Trial Design: The sponsor should utilize qualified
individuals(e.g. biostatisticians, clinical pharmacologists, and
physicians)

5.Trial Management, Data Handling, and
Record Keeping:
The sponsor should utilize appropriately qualified
individuals to supervise the overall conduct of the
trial, to handle the data, to verify the data, to conduct
the statistical analyses, and to prepare the trial
reports
If the sponsor discontinues the clinical development
of an investigational product, the sponsor should
notify all the trial investigators/institutions and all
the regulatory authorities

 6)CompensationtoSubjectsandInvestigators:
 The sponsor should provide insurance the
investigator/the institution against claims arising
from the trial
 The sponsor's policies and procedures should
address the costs of treatment of trial subjects in the
event of trial-related injuries

DUTIES
 (a) Ensure timely delivery of investigational product
to the investigator
 (b). Maintain a system for the disposition of unused
investigational product
 (c).Maintain records that document shipment,
receipt, disposition, return, and destruction of the
investigational product
 (d). Take steps to ensure that the investigational
product are stable over the period of use

CLINICAL TRIAL PROTOCOL AND PROTOCOL
AMENDMENT
1. General Information:
 Protocol title, protocol identifying number, and date
 Name and address of the sponsor
 Name and title of the person authorized to sign the
protocol
 Name, title, address, and telephone number of the
sponsor's medical expert (or dentist when appropriate)
for the trial
 Name and title of the investigator who is responsible for
conducting the trial
 Name, title, address, and telephone number(s) of the
qualified physician

2.Trial Objectives and Purpose
3.Trial Design: A description of the type/design of trial to be conducted
(e.g. double-blind, placebo-controlled, parallel design) and a schematic
diagram of trial design, procedures and stages.
A description of the trial treatment and the dosage and dosage regimen
of the investigational product
4. Selection and Withdrawal of Subjects:
Subject inclusion criteria
Subject exclusion criteria
Subject withdrawal criteria

 5. Treatment of Subjects:The treatment to be
administered, including the name of all the product,
the dose, the dosing schedule, the route/mode of
administration, and the treatment period
 6. Assessment of Efficacy: Recording, and
analysing of efficacy parameters.
 7. Assessment of Safety: The methods and timing
for assessing, recording, and analysing safety
parameters.

INVESTIGATOR’S BROCHURE
 The Investigator's Brochure is a compilation of the
clinical and nonclinical data on the investigational
product that are relevant to the study of the product
in human subjects
 1.Purpose: To facilitate their understanding of the
rationale for such as the dose, dose
frequency/interval, methods of administration and
safety monitoring procedures

2. General Considerations
 The IB should include:
 Title Page
 Confidentiality Statement
3. Contents of the Investigator’s Brochure:
a).Introduction:A brief introductory statement should be provided that
contains the chemical name of the investigational product, all active
ingredients, the investigational product pharmacological class
b).Physical, Chemical, and Pharmaceutical Properties and
Formulation:A description should be provided of the investigational
product substance(including the chemical and structural formula)

 C).Nonclinical Studies : The information provided may
include the following
• Number and sex of animals in each group
• Unit dose (e.g. (mg/kg))
• Dose interval
• Route of administration
• Duration of dosing
• Results including the following aspects:
− Time to onset of effects
− Reversibility of effects
− Duration of effects
− Dose response

(a).Nonclinical Pharmacology: potential therapeutic
activity, assess safety
(b).Pharmacokinetics and Product Metabolism in Animals:
biological transformation and disposition of the
investigational product in all species studied should be
given.
(c) Toxicology: − Single dose
− Repeated dose
− Carcinogenicity
− Special studies (e.g. irritancy and sensitisation)
− Reproductive toxicity
− Genotoxicity (mutagenicity)

d).Effects in Humans: pharmacokinetics, metabolism,
pharmacodynamics, dose response, safety, efficacy, and
other pharmacological activities
Pharmacokinetics and Product Metabolism in Humans:−
Bioavailability of the investigational product
− Interactions (e.g., product-product interactions and
effects of food).
Safety and Efficacy: The IB should provide a description of
the possible risks and adverse drug reactions
Marketing Experience: The IB should identify countries
where the investigational product has been marketed or
approved.

ESSENTIAL DOCUMENTS FOR THE CONDUCT
OF A CLINICAL TRIAL
 which individually and collectively permit evaluation of the
conduct of a trial and the quality of the data produced.
 These documents serve to demonstrate the compliance of
the investigator, sponsor and monitor with the standards of
Good Clinical Practice and with all applicable regulatory
requirements
 The minimum list of essential documents which has been
developed follows:
 Before the Clinical Phase of the Trial:
1).investigator’s brochure

2).Signed protocol and amendments
3).Financial aspects of the trial
4).Insurance statement
5).Signed agreement between involved parties
6).Institutional review board/independent ethics committee
composition
7).Curriculum vitae and other relevant documents evidencing
qualifications of investigator
8).Instructions for handling of investigational product and
trial-related materials
9). decoding procedures for blinded trials

 During the clinical conduct of the trial:
 Investigator’s brochure updates: any revision to
protocol/amendment,CRF, informed consent form
 curriculum vitae for new investigator
 signed, dated and completed case report forms (CRF)
 documentation of CRF corrections
 notification by originating investigator to sponsor of
serious adverse events and related reports

 After Completion or Termination of the Trial:
 Investigationalproductaccountabilityatsite
 Documentationofinvestigationalproductdestruction
 Final trial close-out monitoring report
 Treatment allocation and decoding documentation
 clinical study report

Introduction
 Designed primarily to increase scientific knowledge about
disease and condition(physical and socio-behavioural)
 It includes their detection, cause and strategies for health
promotion, prevention of disease

CONTENT
 ICMR
 SCHEDULE Y

INDIAN COUNCIL OF MEDICAL
RESEARCH

ICMR
 The Indian Council of Medical Research (ICMR), the
apex body in India for the formulation, coordination and
promotion of biomedical research, is one of the oldest and
largest medical research bodies in the world. The ICMR is
funded by the Government of India through the
Department of Health Research, Ministry of Health and
Family Welfare
 The Council's research priorities coincide with National
health priorities such as control and management of
communicable diseases

Background
 Second World War (1939-45) trial of German
medical practitioners accused of conducting
experiments on human participants without their
consent and exposing them to grave risk of death
 Thus, the first International Statement on the ethics of
medical research using human subjects namely, the
Nuremberg Code was formulated in 1947
 In 1948, Universal Declaration of Human Rights
(adopted by the General Assembly of the United
Nations) expressed concern about rights of human
beings being subjected to involuntary maltreatment.

 In 1966, the International Covenant on Civil and Political
Rights specifically stated, ‘No one shall be subjected to
torture or to cruel, inhuman or degrading treatment or
punishment. In particular, no one shall be subjected
without his consent to medical or scientific treatment.’
 In February 1980, the Indian Council of Medical
Research released a ‘Policy Statement on Ethical
Considerations involved in Research on Human Subjects’
for the benefit of all those involved in clinical research in
India

 In 1982, the World Health Organisation (WHO) and the
CIOMS issued the ‘Proposed International Guidelines for
Biomedical Research involving Human Subjects

Governing body
 The Governing Body of the Council is presided over by
the Union Health Minister
 Assisted by a series of Scientific Advisory Groups, Scientific
Advidsory Committees, Expert Groups, Task Forces,
Steering Committees etc. which evaluate and monitor
different research activities of the Council.

General consideration
1.The purpose of such research is that it should be directed
toward the increase of knowledge about the human
condition
2. Such research is conducted under conditions that no
person or persons become a mere
3.such research must be subjected to a regime of evaluation at
all stage of the proposal

GENERAL PRINCIPLE
1).Principle of essentiality : mean for the benefit of all
members of the human species
2).Principle of voluntariness ,informed consent and
community agreement:
Where any such research entails treating any community or
group of persons as a research participant, these principles
of voluntariness and informed consent shall apply

3.Principle of non expolitation: research participants
are remunerated for their involvement in the research or
experiment, each research shall include an in built
mechanism for compensation for the human participants
either through insurance cover or any other appropriate
means to cover all foreseeable and unforseeable risk
4. Principle of privacy and confidentiality: where the
identity and records of the human participants of the
research or experiment are confidential
5.Principle of precaution and risk minimization:
To ensure that the research participants and those affected
by it including community are put to the minimum risk

6).Principle of professional competence: The research
is conducted by qualified person who act with total integrity
7). Principle of accountability and transparancy:
Whereby the research or experiment will be conducted in a
fair, honest,impartial and transparent manner

ETHICAL REVIEW PROCEDURES
 It is mandatory that all proposals on biomedical research
involving human participants should be cleared by an
appropriately constituted Institutional Ethics Committee
(IEC), also referred to as Institutional Review Board (IRB),
Ethics Review Board (ERB) and Research Ethics Board
(REB) in other countries, to safeguard the welfare and the
rights of the participants
 They have the responsibility of regular monitoring of the
approved programmes to foresee the compliance of the
ethics during the period of the project

BASIC RESPONSIBILITIES
1.The IRB has the responsibility and the authority to
approve/reject or ask for modification in the trial
2. The investigator are required to forward to the IRB all
serious adverse event reports, which the IRB should evaluate
to check whether subjects are at undue risks
3.To protect the dignity, rights and well being of the potential
research participants.
4.Oversight the safety of the drug under trial
5.All suspected unexpected serious adverse reaction report
should also be forwarded to the IRB for review

COMPOSITION
1. Chairperson
2. Two persons from basic medical science area
3. Two clinicians from various Institutes
4. One legal expert or retired judge
5. One social scientist
6. One philosopher/ ethicist/ theologian
7. One lay person from the community
8. Member Secretary

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 IEC’s 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

1)Exemtion from review: Proposals which present less
than minimal risk fall under this category
2)Expedited Review: The proposals presenting no more
than minimal risk to research participants may be
subjected to expedited review.
3).Full Review: All research presenting with more than
minimal risk, proposals/ protocols which do not qualify for
exempted or expedited review and projects that involve
vulnerable population and special groups shall be subjected
to full review by all the members

IRB MEETINGS
 Meeting should be held periodically
 Member secretary of the IRB convenes the meeting
at a suitable location and time and informs all the
members of the same
 During IRB meeting free discussion should be
allowed
 If a member wishes his or her point to be specifically
mentioned, the member is allowed to do so

IRB DECISION
 The IRB may take a decision on the basis of majority
opinion
 There is a standard format in which the approval has
to be conveyed
 In case the IRB has some suggestion to make
regarding any aspect of the trial ,they are free to
record them in their letter of approval
 If the IRB is rejecting the proposal then reasons for
rejection should be included in the letter

IRB DOCUMENATION
 The IRB files must contain an updated list of
members serving on the board, which states their
names, qualifications, affiliations and even their
gender
 The IRB must have written standard operation
procedures regarding its functioning. This would
generally include method for invitation of members,
fees of the IRB, meeting schedule, documents to be
submitted. SOPs are generally considered
confidential document

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*
1.The title with signature of Principal Investigator (PI) and Co
investigators as attestation for conducting the study.
2. Research objectives
3. Recent curriculum vitae of the Investigators indicating
qualification and experience.
4.Inclusion and exclusion criteria for entry of participants

5. Description of methodology of the proposed research
6.Plan to withdraw or withhold standard therapies in the
course of research
7.Plan for statistical analysis of study
8.Procedure for seeking and obtaining informed consent with
sample of patient information sheet and informed consent
forms in English and local languages
9.Safety of proposed intervention and any drug or vaccine to
be tested, including results of relevant laboratory, animal
and human research
10. For research involving more than minimal risk, an
account of management of such risk or injury

11.Proposed compensation and reimbursement of incidental
expenses and management
12. An account of storage and maintenance of all data
collected during the trial.
13. Plans for publication of results - positive or negative -
while maintaining the privacy and confidentiality of the
study participants
14.Agreement to comply with national and international
Good Clinical Practices (GCP) protocols for clinical trials.
15. Details of Funding agency/ Sponsors and fund allocation

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

General ethical issue
 Alltheresearchinvolvinghumanparticipantsshouldbeconductedin
accordance with the four basic ethical principles, namely autonomy
(respect for person / participant) beneficence, non-maleficence (do
noharm)andjustice
 The Principal Investigator is the person responsible for not only
undertakingresearchbutalsoforobservanceoftherights,healthand
welfareoftheparticipants

 INFORMED CONCENT PROCESS
 Informed consent protects the individual’s freedom of
choiceandrespectforindividual
 Adequate information about the research is given in a
simple and easily understandable unambiguous language
in a document known as the Informed Consent Form
withParticipant/PatientInformationSheet

COMPENSATION FOR PARTICIPATION
 During the period of research if the participant requires
treatment for complaints other than the one being studied
necessary free ancillary care or appropriate referrals may
be provided
 All payments, reimbursement and medical services to be
provided to research participants should be approved by
the IEC
 Care should be taken:
 when a participant is withdrawn from research for medical
reasons related to the study the participant should get the
benefit for full participation

SELECTION OF SPECIAL GROUPS AS RESEARCH
PARTICIPANTS
 Pregnant or nursing women:
 Pregnant or nursing women should in no circumstances be
the participant of any research unless the research carries
no more than minimal risk to the fetus or nursing infant
and the object of the research is to obtain new knowledge
about the foetus, pregnancy and lactation.
 As a general rule, pregnant or nursing women should not
be participants of any clinical trial except such trials as are
designed to protect or advance the health of pregnant or
nursing women or foetuses or nursing infants, and for
which women who are not pregnant or nursing would not
be suitable participants.

 Children: Before undertaking trial in children the
investigator must ensure that:
A. children will not be involved in research that could be
carried out equally well with adults;
B. The purpose of the research is to obtain knowledge
relevant to health needs of children. For clinical evaluation
of a new drug the study in children should always be carried
out after the phase III clinical trials in adults. It can be
studied earlier only if the drug has a therapeutic value in a
primary disease of the children;
C. a parent or legal guardian of each child has given proxy
consent

 Vulnerable groups: Effort may be made to ensure that
individuals or communities invited for research be selected
in such a way that the burdens and benefits of the research
are equally distributed.
 Persons who are economically or socially disadvantaged
should not be used to benefit those who are better off than
them

ESSENTIAL INFORMATION ON CONFIDENTIALITY FOR
PROSPECTIVE RESEARCH PARTICIPANTS
 Safeguarding confidentiality:
 Data of individual participants can be disclosed under the
following circumstances :
 a. only in a court of law under the orders of the presiding
judge
 b. there is threat to a person’s life or
 c. in cases of severe adverse reaction may be required to
communicate to drug registration authority

COMPENSATION FOR ACCIDENTAL INJURY
 Obligation of the sponsor to pay: The sponsor whether
a pharmaceutical company, a government, or an institution,
should agree, before the research begins, in the prior
agreement to provide compensation for any physical or
psychological injury for which participants are entitled or
agree to provide insurance coverage for an unforeseen
injury whenever possible

SCHEDULE Y
 REQUIREMENTS AND GUIDELINES FOR PERMISSION TO
IMPORT OR MANUFACTURE OF NEW DRUGS FOR SALE OR
TO UNDERTAKE CLINICAL TRIALS:
Application for permission: following data in accordance
with the appendices, namely
a) chemical and pharmaceutical information
b) Animal pharmacology data
1.Specific pharmacological actions and demonstrating,
therapeutic potential for humans shall be described according to
the animal models and species used. Wherever possible, dose-
response relationships and ED50 shall be submitted. Special
studies conducted to elucidate mode of action

2.pharmacokinetic data related to the absorption,
distribution, metabolism and excretion of the test
substance
4.animal toxicology data
5.human Clinical Pharmacology:
(a) for new drug substances discovered in India, clinical trials
are required to be carried out in India right from Phase I
(b) for new drug substances discovered in countries other
than India, Phase I data should be submitted along with
the application

After submission of Phase I data generated outside India to the
Licensing Authority, permission may be granted to repeat Phase
I trials and/or to conduct Phase II trials and subsequently Phase
III trials concurrently with other global trials for that drug. Phase
III trials are required to be conducted in India before permission
to market the drug in India is granted
(c).The data required will depend upon the purpose of the new
drug application. The number of study subjects and sites to be
involved in the conduct of clinical trial will depend upon the
nature and objective of the study
(d).Application for permission to initiate specific phase of clinical
trial should also accompany Investigator's brochure, proposed
protocol, case record form, study subject's informed consent
document(s), investigator's undertaking and ethics committee
clearance, if available

5.Regulatory status in other countries, including Information
in respect of restrictions imposed, if any, on the use of the
drug in other countries, e.g. dosage limits, exclusion of
certain age groups, warning about adverse drug reactions
6.The full prescribing information should be submitted as
part of the new drug application for marketing
7.complete testing protocol/s for quality "control testing
together with a complete impurity profile

CLINICAL TRIAL
(1) Approval for clinical trial:
A. Clinical trial on a new drug shall be initiated only after the
permission has been granted by the Licensing Authority and
the approval obtained from the respective ethics committee
B. All trial Investigator should possess appropriate qualifications,
training and experience and should have access to such
investigational and treatment facilities as are relevant to the
proposed trial protocol
C. A qualified physician (or dentist, when appropriate) who is an
investigator or a sub-investigator for the trial, should be
responsible for all trial-related medical (or dental) decisions.
Laboratories used for generating data for clinical trials should
be compliant with Good Laboratory Practices

D. Protocol amendments if become necessary before
initiation or during the course of a clinical trial, all such
amendments should be notified to the Licensing Authority
in writing along with the approval by the ethics committee
which has granted the approval for the study.
Administrative and/or logistic changes in the protocol
should be notified to the Licensing Authority within 30
days

Responsibilities of Sponsor:
(i).The clinical trial Sponsor is responsible for:
implementing and maintaining quality assurance systems
to ensure that the clinical trial is conducted and data
generated, documented and reported in compliance with
the protocol and Good Clinical Practice (GCP) Guidelines
issued by the Central Drugs Standard Control Organization,
Directorate General of Health Services, Government of
India as well as with all applicable statutory provisions
(ii) Sponsors are required to submit :a status report on
the clinical trial to the Licensing Authority at the prescribed
periodicity.

iii) Any unexpected serious adverse event (SAE) (as defined
in GCP Guidelines) occurring during a clinical trial should
be communicated promptly (within 14 calendar days) by
the Sponsor to the Licensing Authority and to the other
Investigator(s) participating in the study

Responsibilities of the Investigator
 The Investigator(s) shall be responsible for the conduct of
the trial according to the protocol and the GCP Guidelines
 During and following a subject's participation in a trial, the
investigator should ensure that adequate medical care is
provided to the participant for any adverse events.
Investigatons) shall report all serious and unexpected
adverse events to the Sponsor within 24 hours and to the
Ethics Committee that accorded approval to the study
protocol within 7 working days of their occurrence

Informed Consent
 In all trials, informed, written consent is required to be
obtained from each study subject. The Investigator must
provide information about the study verbally as well as
using a patient information sheet, in a language that is non-
technical and understandable by the study subject. The
Subject's consent must be obtained in writing using an
'Informed Consent Form
 A checklist of essential elements to be included in the study
subject's informed consent document as well as a format for
the Informed Consent Form for study Subjects

Responsibilities of the Ethics Committee:
 It is the responsibility of the ethics committee that reviews
and its approval to a trial protocol to safeguard the rights,
safety and well being of all trial subjects.
 The ethics committee should exercise particular care to
protect the rights, safety and well being of all vulnerable
subjects participating in the study, e.g., members of a group
with hierarchical structure (e.g, prisoners, armed forces
personnel, staff and students of medical, nursing and
pharmacy academic institutions), patients with incurable
diseases,

Human Pharmacology (Phase I):
 The objective of studies in this Phase is the estimation of
safety and tolerability with the initial administration of an
investigational new drug into humans Studies in this Phase
of development usually have non-therapeutic objectives
and may be conducted in healthy volunteers subjects or
certain types of patients
 Phase I trials should preferably be carried out by
Investigators trained in clinical pharmacology with access
to the necessary facilities to closely observe and monitor the
Subjects.

Studies conducted in phase 1
maximum tolerated
dose Pharmacokinetic
Pharmacodynamic
Early measurement of drug
toxicity

Therapeutic exploratory trials (Phase II)
 The primary objective of Phase II trials is to evaluate the
effectiveness of a drug for a particular indication or
indications in patients with the condition under study and
to determine the common short-term side-effects and risks
associated with the drug
 These studies should be closely monitored.
 Doses used in Phase II are usually (but not always) less
than the highest doses used in Phase 1
 If the application is for conduct of clinical trials as a part of
multi-national clinical development of the drug, the
number of sites and the patients as well as the justification
for undertaking such trials in India shall be provided to the
Licensing Authority

Therapeutic confirmatory trials (Phase III):
 Studies in Phase III are designed to confirm the
preliminary evidence accumulated in Phase II that a drug is
safe and effective for use in the intended indication and
recipient population
 Studies in Phase III may also further explore the dose-
response relationships(relationships among dose, drug
concentration in blood and clinical response), use of the
drug in wider populations, in different stages of disease, or
the safety and efficacy of the drug in combination with
other drug

 For new drugs approved outside India,:
Phase III studies need to be carried out primarily to
generate evidence of efficacy and safety of the drug in
Indian patients when used as recommended in the
prescribing information.
Prior to conduct of Phase III studies in Indian subjects,
Licensing Authority may require pharmacokinetic studies
to be undertaken to verify that the data generated in Indian
population is in conformity with the data already generated
abroad

Post Marketing Trials (Phase IV):
 Post Marketing trials are studies (other than routine
surveillance) performed after drug approval are related to
the approved indication
 These trials go beyond the prior demonstration of the
drug's safety, efficacy and dose definition
 Phase IV trials include additional drug-drug interaction(s),
dose-response or safety studies and trials designed to
support use under the approved indication, e.g.
mortality/morbidity studies, epidemiological studies etc

Studies in special populations:
 Geriatrics: Geriatric patients should be included in
Phase III clinical trials
 (a) the disease intended to be treated is
characteristically a disease of aging
 (b) when there is specific reason to expect that
conditions common in the elderly
 (c) when the new drug is likely to alter the geriatric
patient's response (with regard to safety or efficacy)
compared with that of the non-geriatric patient.

 Paediatrics:
 For a drug expected to be used in children, evaluations
should be made in the appropriate age group
 If the new drug is intended to treat serious or life-
threatening diseases,lack of data should be justified in
detail.
 In cases where there is limited paediatric data at the time of
submission of application - more data in paediatric patients
would be expected after marketing authorisation for use in
children is granted.

 Pregnant or nursing women: (i).Pregnant or
nursing women should be included in clinical trials only
when the drug is intended for use by pregnant/nursing
women or foetuses/nursing infants and where the data
generated from women who are not pregnant or nursing,
is not suitable.
(ii) For new drugs intended for use during pregnancy,
follow-up data (pertaining to a period appropriate for
that drug) 'on the pregnancy, foetus and child will be
required. Where applicable, excretion of the drug or its
metabolites into human milk should be examined and
the infant should be monitored for predicted
pharmacological effects of the drug.

Post Marketing Surveillance
 Subsequent to approval of the product, new drugs should
be closely monitored for their clinical safety once they are
marketed.
(a) report all the relevant new information from appropriate
sources
(b) relate these data to patient exposure
(c) summarize the market authorization status 1U different
countries and any significant variations related to safety
(d) indicate whether changes should be made to product
information in order to optimize the use of the product.

REFERENCES
1).ICH Harmonized tripartite guideline guideline for good
clinical practice E6(R1) ,Current Step 4 version dated 10
June 1996
 2).Ethical guidelines for biomedical research on human
participants, Published by: Director-General Indian
Council of Medical Research New Delhi 110029, October,
2006
 3).http://cdsco.nic.in/html/D&C_Rules_Schedule_Y.pd
f
 4)https://www.fda.gov/downloads/regulatoryinformatio
n/guidances/ucm512761.pd

 5).Ghooi .B.R Principle of clinical research,first
edition; publised by nirali prakashan page no 3.19-
3.24

Assignment on Regulatory Prespectives of Clinical Trials

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