Vels University, Chennai. I declare that, Made these slides - All information Web sources only.

1. Introduction
History
Clinical Trials (Different Phases)
Scope
CLINICAL RESEARCH
Dr. B. Sampath Kumar
Vels university, Chennai

2.  Is an organized research conducted on
human beings
 Intended to provide adequate information
on the use of drugs as a therapeutic
agent, with regard to
– Usefulness
– Safety
– Adverse effects
INTRODUCTION

5. The world's first clinical trial is recorded in the
“Book of Daniel” in The Bible.
Nebuchadnezzar ordered his people to eat
only meat and drink only wine, a diet he
believed would keep them in sound physical
condition.
But several young men of royal blood, who
preferred to eat vegetables, objected. The king
allowed these rebels to follow a diet of
legumes and water — but only for 10 days.
When Nebuchadnezzar's experiment ended,
the vegetarians appeared better nourished
than the meat-eaters,
so the king permitted the legume lovers to
continue their diet. This probably was the one
of the first times in evolution of human species
that an open uncontrolled human experiment
guided a decision about public health.
HISTORY 562 AD
King - Nebuchadnezzar
a resourceful military leader

6. Avicenna (1025 AD)
‘Canon of Medicine’ describes some
interesting rules for the testing of
drugs. He suggests that in the clinical trial
a remedy should be used in its natural
state in disease without complications. He
recommends that two cases of contrary
types be studied and that study be made
of the time of action and of the
reproducibility of the effects. These rules
suggest a contemporary approach for
clinical trials.
Clinical Trials physician - Described concepts
for experimental testing of drugs. Eg - quality
of the drug, species specific .
Avicenna

7. The first clinical trial of a novel therapy was conducted
accidentally by the famous surgeon Ambroise Pare in
1537. In 1537 while serving with the Mareschal de
Motegni he was responsible for the treatment of the
battlefield wounded soldiers. As the number of
wounded was high and the supply of conventional
treatment – oil was not adequate to treat all the
wounded, he had to resort to unconventional
treatment.
He describes,' at length my oil lacked and I was
constrained to apply in its place a digestive made of
yolks of eggs, oil of roses and turpentine. That night I
could not sleep at any ease, fearing that by lack of
cauterization I would find the wounded upon which I
had not used the said oil dead from the poison. I
raised myself early to visit them, when beyond my
hope I found those to whom I had applied the
digestive medicament feeling but little pain, their
wounds neither swollen nor inflamed, and having
slept through the night. The others to whom I had
applied the boiling oil were feverish with much pain
and swelling about their wounds. Then I determined
never again to burn thus so cruelly the poor wounded
by arquebuses’. However, it would take another 200
years before a planned controlled trial would be
organized.
Ambroise Pare - 1537

8. James Lind and Scurvy Trial - 1747
James Lind thought that acidic foods might
cure scurvy.
He assigned 12 sailors with scurvy into one of
six groups. All men then received the same
daily diet plus: 1.Group one - A quart of cider
daily 2.Group two – Twenty-five drops of elixir
of vitriol (sulfuric acid) 3.Group three - Six
spoonfuls of vinegar 4.Group four - Half a pint
of seawater 5.Group five - Two oranges and
one lemon 6.Group six - A spicy paste plus a
drink of barley water At the end of 6 days, one
sailor from group five was fit for duty and the
second had almost recovered. Other than
these two men, only the sailors from group
one showed some effect of their treatment

9. 1800: Arrival of Placebo
(a harmless pill, medicine, or
procedure prescribed more for the psychological benefit to the patient than for any physiological effect)
in 1863 that United States physician Austin Flint
planned the first clinical study comparing a dummy
remedy to an active treatment. He treated 13
patients suffering from rheumatism with an herbal
extract which was advised instead of an established
remedy.
In 1886, Flint described the study in his book A
Treatise on the Principles and Practice of Medicine.
“This was given regularly, and became well known
in my wards as the ‘placeboic remedy’ for
rheumatism. The favorable progress of the cases
was such as to secure for the remedy generally the
entire confidence of the patients.”

10. The Medical Research Council (MRC) UK carried out a trial in 1943 to investigate patulin
treatment for (an extract of Penicillium patulinum) the common cold.
This was the first double blind comparative trial with concurrent controls in the general
population in recent times.
The MRC Patulin Clinical Trials Committee (1943) was chaired by Sir Harold Himsworth, and its
statisticians were M Greenwood and W J Martin. This nationwide study enrolled over a thousand
British office and factory workers suffering from colds. This was quite a challenging endeavor in
wartime,
The study was rigorously controlled by keeping the physician and the patient blinded to the
treatment. The treatment allocation was done using an alternation procedure. A nurse allocated
the treatment in strict rotation in a separate room. The nurse filed the record counterfoil
separately, and detached the code label for the appropriate bottle before asking the patient to
visit the doctor.
The statisticians considered this an effective random concurrent allocation. .However, the
outcome of the trial was disappointing as the analysis of trial data did not show any protective
effect of patulin.
1943: The First Double blind Controlled Trial - Patulin for Common Cold

11. The idea of randomization was introduced in 1923. However, the first
randomized control trial of streptomycin in pulmonary tuberculosis
was carried out in 1946 by MRC of the UK.
The MRC Streptomycin in Tuberculosis Trials Committee (1946) was
chaired by Sir Geoffrey Marshall, and the statistician was Sir Austin
Bradford Hill and Philip Hart, who later directed the MRC's
tuberculosis research unit, served as secretary. Marc Daniels, as the
“registrar” coordinated the clinicians at the participating hospitals.
The trial began in 1947.
1946 First Randomized Curative Trial - The Randomized Controlled
Trial of Streptomycin

12. Evolution of Ethical and Regulatory Framework
Clinical trials started to become embodied in regulation as
government authorities began recognizing a need for
controlling medical therapies in the early 20th century.
The FDA was founded in 1862 as a scientific institution and
became a law enforcement organization after the US
Congress passed the Food and Drugs Act in 1906. After
that, legislation progressively demanded greater
accountability for marketing food and drugs and the need
for testing drugs in clinical trials increased.
The regulatory and ethical milieu will continue to evolve as
new scientific disciplines and technologies become part of
drug development.

13. India has recently been recognized as an attractive country
for clinical trials. But the country's journey in clinical
research field has a long history. India has a rich heritage of
traditional medicine – Ayurveda. The classic ayurvedic texts
contain detailed observations on diseases and in-depth
guidance on remedies. It is likely that these descriptions
are based on direct observations made by the ancient
ayurveda experts. However, there is no recorded
documentation in the ancient texts of any clinical
experiments.

14. The major historic milestones of the Indian Council of Medical Research reflect, in
many ways, the growth and development of medical research in the country over
the last nine decades.
First meeting of the Governing Body of the Indian Research Fund Association
(IRFA) was held on November 15, 1911 at the Plague Laboratory, Bombay, under
the Chairmanship of Sir Harcourt Butler.
At the 2nd meeting of the Governing Body in 1912, a historic decision was taken
to start a journal for Indian Medical research. Between 1918--20, several projects
on beriberi, malaria, kala azar and indigenous drugs were initiated.
In 1945, a Clinical Research Unit – the first research unit of IRFA attached to a
medical institution- was established at the Indian Cancer Research Centre,
Bombay.
In 1949, IRFA was redesignated as the Indian Council of Medical Research.
Over next 60 years, ICMR established many national research centers in the fields
of nutrition, tuberculosis, leprosy, viral disease, cholera, enteric disease,
reproductive disorders, toxicology, cancer, traditional medicine, gas disaster,
genetics, AIDS etc.

15. What is clinical trial ??
“A systematic study of pharmaceutical products on human subjects
(whether patients or non patients volunteers) in order or verify the
clinical, pharmacological (including pharmacodynamics and
pharmacokinetics) and or adverse effects, with the object of
determining their safety and efficacy”
Clinical Trials (Different Phases)

16. Why Are Clinical Trials Important?
Does the new treatment work in humans?
 Is the new treatment safe?
Clinical trials,
 Answer critical research questions
 Find better treatments and ways to prevent disease
 Translate results of basic scientific research into better ways to
prevent, diagnose, or treat disease.

17. Types of Clinical Trials:
Diagnostic Trials - determine better tests or
procedures for diagnosing a particular disease
or condition.
Screening Trials - test the best way to detect or
treat diseases.
Quality of Life Trials - explore and measure
ways to improve the comfort and quality of life
of people with a chronic illness.
Treatment Trials - test new treatments, new
combination of drugs or new approaches to
surgery or radiation.
Prevention Trials - look for better ways to
prevent diseases.

18. Clinical Trials are Done in Phases:
• First, a Pre-Clinical Trial must be done before the Clinical
Trial starts.
• Preclinical trial –
research on a new drug or a new medical device or
procedure, usually done on animals, to learn about
mechanisms of action, determine how well the treatment
works, and see if it is safe to test on humans.

19. Phase I
• Researchers test an experimental drug or treatment
in a small group of people (approximately 20-80) for
the first time. The purpose is to evaluate its safety
and identify side effects. If this is a veterinary study,
it is conducted in animals.

20. Phase II
• The experimental drug or treatment
is administered to a larger group of
people/animals (approximately100-
300) to determine its effectiveness
and to further evaluate its safety.

21. Phase III
• The experimental drug or treatment is administered to a large group
of people/animals (300-3,000 or more) to confirm its effectiveness,
monitor side effects, and compare it with standard or equivalent
treatments.

22. Phase IV
• After a drug is licensed (approved by the FDA) or treatment
is launched, researchers track its safety, seeking more
information about a drug or treatment’s risks, benefits, and
optimal use.
• These long-term studies involve large groups of participants
and are designed to reveal if any unexpected side effects
occur in a small percentage of individuals.

23. • Clinical trials are usually sponsored
or funded by companies that make
pharmaceuticals or medical devices.
• Trials can occur at sites as varied as
hospitals, universities, doctors’
offices, community clinics, or in the
offices of clinical-trial contractors.

24. PHARMACEUTICAL ENTERPRISE

25. Success rates

26. Pharmaceutical companies
R&D department
Clinical research managers
Research coordinators
Regulatory affairs managers
Data managers
Medical writers
 DCGI
Ethics committee
Hospitals
Accredited laboratories
 Doctors ( Clinicians)
Contract/ Clinical Research Organizations
STAKE HOLDERS IN CLINICAL RESEARCH

28. Why Career in Clinical Research?
Fastest growing segment in the healthcare / pharmaceutical
industry
Excellent Opportunity to Develop Combination of Technical and
Management Skill Development
Part of the Global Growth Opportunity
Wider Job Horizon
Rapidly Growing Opportunities… (internal and external)
Higher Job Satisfaction
Continuous Training Opportunities
Overseas Job Opportunities