In these slides you can get the information of clinical trials which have four phase I,II,III, IV. before clinical trials, Pre-clinical studies should be completed.

1. Introduction to
Clinical Trial
Submitted By :
Abu Bakr Ansari
Pharm. D 5th Year
Roll No. 1601096001
Enroll No. 1600100627
Submitted To :
Dr. Mohd Ajmal Sir
Assistant Professor
Integral University, Lucknow
Faculty of Pharmacy
PRY – 501 Clinical Research

2. Table of Content
 Definition and Importance
 Role of Clinical trials in Clinical Product Development
Different types of Clinical trials and their phases
Important Regulations and Guidelines – ICH & GCP
Design of a Clinical Trial

3. What is Clinical Trials
• Clinical trials are scientific investigations that
examine and evaluate safety and efficacy of
different therapies in human subjects. There are
various definitions available as different individuals
have tried to which try to capture the essence of
clinical trials at different times, e.g.
 Meinert (1986) indicates that a clinical trial is a
research activity that involves administration of a
test treatment to some experimental unit in order
to evaluate the treatment.
 Piantadosi (1997) simply defined a clinical trial
as an experimental testing o
f medical treatment
on human subject.

4. • The Code of Federal Regulations (CFR) defines a
clinical trial as the clinical investigation of a drug
that is administered or dispensed to, or used
involving one or more human subjects (21 CFR ).
• Three important key words in these definitions
of clinical trials are experimental unit, treatment,
and evaluation of the treatment.

5. Experimental Unit
• An experimental unit is usually referred to
as a subject from a targeted population
under study. Therefore the experimental
unit is usually used to specify the intended
study population to which the results of
the study are inferred. For example, the
intended population could be patients
with certain diseases at certain stages or
healthy human subjects.

6. Treatment
• identity (e.g., a compound or drug), a new
diet, a surgical procedure, a diagnostic test,
a medial device, a health education
program, or no treatment. Other examples
include surgical excision, radiotherapy, and
chemotherapy as a combination of surgical
procedure and drug therapy for breast
cancer; magnetic resonance imaging (MRI)
with a contrast imaging agent as a
combination of diagnostic test and a drug for
enhancement of the efficacy of a diagnostic
test.

7. Evaluation
• In addition to the traditional evaluation of
effectiveness and safety of a test treatment,
clinical trials are also designed to assess
quality of life, pharmacogenomics, and
pharmacoeconomics such as cost-
minimization, cost-effectiveness, and cost-
benefit analyses to human subjects
associated with the treatment under study. It
is therefore recommended that clinical trials
should not only evaluate the effectiveness
and safety of the treatment but also assess
quality of life, impact of genetic factors,
pharmacoeconomics, and outcomes
research associated with the treatment.

8. Differnet Phases of Clinical Trials
• Clinical trials involving new drugs are
commonly classified into four phases (I, II,
III and IV). Each phase of the drug approval
process is treated as a separate clinical trial.
If the drug successfully passes through
Phases I, II, and III, it will usually be
approved by the national regulatory authority
for use in the general population. Phase IV
are 'post-approval' studies. Before
pharmaceutical companies start clinical
trials on a drug, they conduct extensive pre-
clinical studies.

9. • Clinical Product Development - Phases

10. The Phases
 PRE-CLINICAL - It involves in vitro (test tube or cell
culture) and in vivo (animal) experiments using wide-
ranging doses of the study drug to obtain preliminary
efficacy, toxicity and pharmacokinetic information. Such
tests assist pharmaceutical companies to decide whether
a drug candidate has scientific merit for further
development as an investigational new drug (IND).
 PHASE I TRIALS: Initial studies to determine the
metabolism and pharmacologic actions of drugs in
humans, the side effects associated with increasing
doses, and to gain early evidence of effectiveness; may
include healthy participants and/or patients.
 PHASE II TRIALS: Controlled clinical studies conducted
to evaluate the effectiveness of the drug for a particular
indication or indications in patients with the disease or
condition under study and to determine the common
short-term side effects and risks.

11.  PHASE III TRIALS: Expanded controlled and
uncontrolled trials after preliminary evidence
suggesting effectiveness of the drug has been
obtained, and are intended to gather additional
information to evaluate the overall benefit-risk
relationship of the drug and provide and adequate
basis for physician labelling.
 PHASE IV TRIALS: Post-marketing studies to
delineate additional information including the drug's
risks, benefits, and optimal use.

12. • Important Terms
INVESTIGATIONAL NEW DRUG (IND): A new drug, antibiotic
drug, or biological drug that is used in a clinical investigation. It
also includes a biological product used in vitro for diagnostic
purposes.
INSTITUTIONAL REVIEW BOARD (IRB): 1. A committee of
physicians, statisticians, researchers, community advocates,
and others that ensures that a clinical trial is ethical and that the
rights of study participants are protected. All clinical trials in the
U.S. must be approved by an IRB before they begin. 2. Every
institution that conducts or supports biomedical or behavioral
research involving human participants must, by federal
regulation, have an IRB that initially approves and periodically
reviews the research in order to protect the rights of human
participants. It is similar to the Independent Ethics Committee
(IEC) outside the United States.

13. NEW DRUG APPLICATION (NDA): An application submitted by
the manufacturer of a drug to the FDA - after clinical trials have
been completed - for a license to market the drug for a
specified indication.
TREATMENT IND: IND stands for Investigational New Drug
application, which is part of the process to get approval from
the FDA for marketing a new prescription drug in the
U.S. It makes promising new drugs available to desperately ill
participants as early in the drug development process as
possible. Treatment INDs are made available to participants
before general marketing begins, typically during Phase III
studies. To be considered for a treatment IND a participant
cannot be eligible to be in the definitive clinical trial.

14. Important Guidelines - ICH
• ICH (International Conference on Harmonisation of Technical
Requirements for Pharmaceuticals for Human use) is a unique
undertaking that brings together the drug regulatory authorities
and the pharmaceutical industry of Europe, Japan and the United
States.
• Regulatory harmonisation offers many direct benefits to both
regulatory authorities and the pharmaceutical industry with
beneficial impact for the protection of public health. Key benefits
include:
 Preventing duplication of clinical trials in humans and minimising
the use of animal testing without compromising safety and
effectiveness;
 Streamlining the regulatory assessment process for new drug
applications;
 Reducing the development times and resources for drug
development.

15.  Q – Quality Guidelines: Defining relevant thresholds for
impurities testing and a more flexible approach to
pharmaceutical quality based on Good Manufacturing
Practice (GMP) risk management.
 S – Safety Guidelines: ICH has produced a comprehensive
set of safety guidelines to uncover potential risks like
carcinogenicity, genotoxicity and reproductive toxicity.
 E – Efficacy Guidelines: The work carried out by ICH
under the Efficacy heading is concerned with the design,
conduct, safety and reporting of clinical trials.
 M – Multidisciplinary Guidelines: Those are the cross-
cutting topics which do not fit uniquely into one of the
Quality, Safety and Efficacy categories. It includes the ICH
medical terminology (MedDRA) and the Common Technical
Document (CTD)

16. Principles of GCP (Good Clinical Practice)
 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).
 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.
 The rights, safety, and well-being of the trial subjects are the
most important considerations and should prevail over
interests of science and society.

17.  The available nonclinical and clinical information on an
investigational product should be adequate to support the
proposed clinical trial.
 Clinical trials should be scientifically sound, and described in
a clear, detailed protocol.
 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.
 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.

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