2. Company Logo History /Back ground
James Lind is seen as the father of clinical trials. As the first to
introduce control groups in 1747, he documented that citrus fruits
in diet could prevent scurvy.
From 1800 onwards, clinical trials became more and more
common, with more attention paid to trial design.
Placebos were first used in 1863.
The idea of randomisation was introduced in 1923.
The first trial using properly randomised treatment and control
groups was carried out in 1948 by the Medical Research Council,
UK. This trial also adopted blind assessment enabling unbiased
analysis of the results.
3. Company Logo Why clinical trials are important
There is a persistent demand and a great need, to develop
new medical treatments that are effective and safe than the
treatments already available in the market.
To enter the market new medicinal products commonly
discovered by means of laboratory research goes into animal
studies followed by clinical trials and then eventually used in
medical care.
4. Company Logo Clinical Trials on Medicinal Products
Clinical trials are the mandatory
bridge between pre-clinical
discovery of new medicinal
products and their general
uses.
This means that clinical trials
must take place before new
research treatments can be
made available to the public,
whether for prescription, over-
the-counter sale or for use in a
clinic.
5. Company Logo Regulatory Authorities requirement
Pre-Clinical NME
File patent application; 17 years for those dated
before June 1995; 20 years for those dated after
June 1995
Pre-Clinical Testing
Assess, safety, biological activity and formulation,.
Duration 6.5 years
File IND application at FDA
Clinical Trials
Phase I
Determine safety and dosage- 1.5 years
Population 20-100
Phase II
Evaluate effectiveness, check side effects; duration
2 yrs
Population 100-500
Phase III
Confirm effectiveness, monitor adverse reactions;
duration 2 yrs; Population 1000-5000
Review and Approval
process
File New Drug Application
(NDA) at FDA
Review duration 1.5 years
Post Marketing Surveillance
Phase IV research Long term safety and effectiveness of treatment
Total # of years 13.5
Over riding principle
Permission by the regulatory authority to allow the
interstate shipment of a drug that, otherwise do not
have a NDA.
Goal is to obtain National Drug Code (NDC)
7. Company Logo Clinical Trial Players and Their
Responsibilities
There are four major players in the clinical trial arena:
Drug regulatory authority
The trial sponsor (sponsor)
Clinical researcher (investigator)
Ethics committee (EC).
8. Company Logo
Sponsors of Clinical Trials
Sponsors of a clinical trial can be either a commercial
company (industry-sponsored 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.
10. Company Logo
Objective of a Clinical Trial
The objective of clinical trials is to evaluate the efficacy
and safety of medicinal products or medical procedures
in humans so new medical treatments can be identified
for medical practice.
11. Company Logo
Definition of a Clinical Trial
A clinical trial is a study designed to answer scientific
questions
Advances in medical treatment have occurred largely due to
knowledge gained from numerous clinical trials that test new and
better ways to treat patients.
Some clinical trials
– Test new treatments,
– Investigate new ways of preventing disorders,
– Screen patients for earlier diagnoses, and
– Monitor the quality of life and/or
– Psychological impact of specific disorders, while others
– Detect disorders in their earlier/ nascent stages
12. Company Logo Clinical Trial (cont.)
The search for good treatments begins with carefully
controlled laboratory research.
The terms "clinical trial" and "clinical study" are
synonymous, but the term "clinical trial" refers to the
process of therapeutic product approval, while a "clinical
study" is related to studies with no particular aim of getting
product approval
13. Company Logo Phases of Clinical trials
The trial phase classification proposed by ICH – in the ICH E8
Guide – is based on the objective of the trial and not just a
sequential number ranging from I-IV:
Human pharmacology
Therapeutic exploratory
Therapeutic confirmatory
Therapeutic use.
14. Company Logo Phase 0 Trials
In recent years, a new trial
phase term has emerged – the
so-called phase 0 (zero) or
micro-dosing trials.
The concept of a phase 0 trial is
an interim step between pre-
clinical research and phase I
studies, where a small number
of human volunteers take small
doses of experimental test
article so there is little risk of
toxicity.
15. Company Logo Human Pharmacology/Phase I Clinical Trials
A human pharmacology trial is typically a phase I trial,
representing the first stage of testing in human participants.
Phase I trials are generally associated with a higher risk of harm
than any other trials, especially the so-called first-into-man trials
and dose escalating trials.
These studies are usually conducted on small populations of
healthy humans. (20-100 volunteers)
Phase I determine a drug's toxicity, absorption, distribution,
metabolism, excretion, duration of action, drug-to-drug interaction
and drug-to-food interaction.
16. Company Logo Phase I trials
Phase I trials are usually
carried out by investigators
trained in clinical
pharmacology and who have
the necessary facilities to
closely observe and monitor
the subjects.
These may be carried out at
one or two centers.
17. Company Logo Therapeutic Exploratory/Phase II
Clinical Trials
After the successful completion
of phase I, an experimental
drug is next tested for safety
and efficacy in a larger
population of individuals
afflicted with the disease or
condition for which the drug
was developed.
Phase II trials primarily aim to
explore therapeutic efficacy in
target patients.
18. Company Logo Therapeutic Confirmatory/Phase III
Clinical Trials
After a drug is shown to be
reasonably effective, it must be
compared with current standard
treatments for the relevant
condition in a large trial involving a
substantial number of participants.
Phase III trials – major
randomised controlled trials –
usually involve 500 to 3,000
participants.
There is usually more than one
phase III trial owing to different
indications. The duration can vary
from a week to many years.
19. Company Logo Therapeutic Use/Phase IV Clinical
Trials
Therapeutic use/phase IV trials begin after a drug has been
approved for distribution or marketing.
In phase IV trials or post-marketing surveillance trials, safety
surveillance – pharmacovigilance – is conducted and ongoing
technical support of that drug is provided.
Other phase IV trials aim to study the effectiveness of treatment
after approval.
20. Company Logo Therapeutic Use/Phase IV Clinical Trials
Therapeutic use trials are not
necessary for approval, but
are regarded as important for
optimizing usage of the drug.
Post-marketing trials can also
be critical for exploring new
uses for a therapy, as well as
acquiring a full understanding
of the capability and uses of a
drug.
22. Company Logo Studies on Women and Children
FDA determined that studies should include
– Women of child-bearing potential
– Pregnant women and
– Children
if the compounds would be used to treat them after
marketing
The rationale is that it is preferable to determine the effects
of the compound under the controlled conditions in clinical
trials as opposed to uncontrolled use of the drug after
marketing
23. Company Logo Studies on Women and Children
1. Conditions levied on trials involving women of child-bearing
potential:
a. Studies are to be carefully monitored and all precautions
taken to minimize exposure in utero
b. Pregnancy testing and establishment of highly effective
methods of birth control
c. May be carried out prior to completion of reproductive
toxicology studies
d. Informed consent process should clearly indicate the
possible risk associated with taking the investigational
drug, since potential risk to the embryo/fetus is unknown
(cont.)
24. Company Logo Studies on Women and Children
2. If pregnant women are to be enrolled in clinical trials, all
reproductive toxicity studies and genotoxicity tests must be
completed. Data from any previous experiences in humans will
also be required
3. If children are to be included in clinical trials,
a) repeated dose toxicity studies,
b) reproductive toxicity and
c) genotoxicity studies should be completed. In addition,
d) safety data from previous studies in human adult populations
should be available
