Introduction to Clinical trial

1. Presented by,
Ms. Sonali B. Diwate
Guided by,
Prof. R. Chanshetti
MODERN COLLEGE OF PHARMACY(FOR WOMEN),
MOSHI, PUNE

2. 1. Introduction to Clinical Trials
2. To understand the importance of Clinical Trials
3. To review and study Phase-I of Clinical Trials
4. To review and study Phase-II of Clinical Trials
5. To review and study Phase-III of Clinical Trials
6. To review and study Phase-IV of Clinical Trials
7. To Summarise the information
To review and study Phases of Clinical Trials
OBJECTIVES

3. Sr No. Particulars
1 Aim and Objectives
2 Introduction to Clinical Trials
3 To understand the importance of
Clinical Trials
4 To review and study Phase-I of Clinical
Trials
5 To review and study Phase-II of Clinical
Trials
6 To review and study Phase-III of Clinical
Trials
7 To review and study Phase-IV of Clinical
Trials
8 To Summarise the information
C
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T
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4. Introduction to Clinical Trial
Trial is from the Anglo–French trier, meaning to try. Broadly, it
refers to the action or process of putting something to a test or
proof.
Clinical is from clinic, from the French cliniqu´e and from the
Greek klinike, and refers to the practice of caring for the sick at
the bedside.
Hence, narrowly, a clinical trial is the action or process of
putting something to a test or proof at the bedside of the sick.
However, broadly it refers to any testing done on human
beings for the sake of determining the value of a treatment for
the sick or for preventing disease or sickness.
The clinical trial, in its simplest form, involves
the application of the experimental variable-
treatment to a person or group of persons and
Observation during or following application of
treatment to measures its effect.

5. Importance to Clinical Trial
Drug input,
Pharmacokinetics,
Pharmacodyanamics,
Pharmacogenetics,
Pharmacogenomics,
Factors affecting Drug response and finally
the toxicity and side effects
It deals with

6. Phase I : First in man  safety
Phase II : First in patient dose, dosage form
Phase III : Efficacy, ADRs
Post marketing surveillance or Phase IV :
Evaluation in the real clinical setting
Assessment of a New Drug in man
can be divided into 4 phases

7. Objectives
1. To assess safe & tolerated dose
2. To see if pharmacokinetics differ much from animal to
man
3. To see if kinetics show proper absorption, bioavailability
4. To detect effects unrelated to the expected action
5. To detect any predictable toxicity
– Inclusion criteria
◦ Healthy volunteers : Uniformity of subjects: age, sex,
nutritional status [Informed consent a must]
◦ Exception: Patients only for toxic drugs Eg AntiHIV,
Anticancer
– Exclusion criteria
◦ Women of child bearing age, children,
Phase I
Preclinical
testing by
clinical
Pharmaco
logist

8. Methods:
◦ First in Man : Small number of healthy volunteers
◦ First in a small group of 20 to 25
◦ Start with a dose of about 1/10 to 1/5 tolerated animal dose
◦ Slowly increase the dose to find a safe tolerated dose
◦ If safe  in a larger group of up to about 50 –75
◦ No blinding
◦ Performed by clinical pharmacologists
◦ Centre has emergency care & facility for kinetics study
◦ Performed in a single centre
◦ Takes 3 – 6 months [ 70% success rate]
Phase I contd

9. First in patient [ different from healthy volunteer]
Early phase [20 – 200 patients with relevant disease]
◦ Therapeutic benefits & ADRs evaluated
◦ Establish a dose range to be used in late phase
◦ Single blind [Only patient knows] comparison with standard drug
Late phase [ 50 – 500]
◦ Double blind
◦ Compared with a placebo or standard drug
Outcomes
◦ Assesses efficacy against a defined therapeutic endpoint
◦ Detailed P.kinetic & P.dynamic data
◦ Establishes a dose & a dosage form for future trials
Takes 6 months to 2 years [ 35% success rate]
Phase II
Clinical
testing by
clinical
Pharmaco
logist

10. Large scale, Randomised, Controlled trials
Target population: 250 – 1000 patients
Performed by Clinicians in the hospital
Minimises errors of phases I and II
Methods
◦ Multicentric  Ensures geographic & ethnic variations
◦ Diff patient subgroups Eg pediatric, geriatric, renal impaired
◦ Randomised allocation of test drug /placebo / standard drug
◦ Double blinded:
◦ Cross over design
◦ Vigilant recording of all adverse drug reactions
◦ Rigorous statistical evaluation of all clinical data
Takes a long time: up to 5 years [25% success]
Phase III
Clinical
Trials by
clinical
Investigators

11. No fixed duration / patient population
Starts immediately after marketing
Report all ADRs
Helps to detect
◦ rare ADRs
◦ Drug interactions
◦ Also new uses for drugs [Sometimes
called Phase V]
Phase IV or Post marketing Surveillance
Post marketing
Surveillance by
Practicing
Clinicians

13. Summary of clinical trial phases
phase primary goal dose patient monitor
typical
number of
participants
notes
Preclinical
Nonhuman efficacy,
toxicity and
pharmacokinetic
information
unrestricted
A graduate level
researcher (Ph.D.)
in vitro and in
vivo animal
Phase 0
Pharmacodynamics and
Pharmacokinetics
particularly oral
bioavailability and half-
life
very small,
subtherapeutic
clinical researcher 10 people
often skipped for
phase I
Phase I
Testing of drug on
healthy volunteers for
dose-ranging
often
subtherapeutic,
but with
ascending doses
clinical researcher 20-100
determines whether
drug is safe to check
for efficacy
Phase II
Testing of drug on
patients to assess
efficacy and safety
therapeutic dose clinical researcher 100-300
determines whether
drug can have any
efficacy; at this point,
the drug is not
presumed to have any
therapeutic effect
whatsoever

14. Phase III
Testing of drug on
patients to assess
efficacy and safety
therapeutic dose
clinical
researcher and
personal
physician
1000-2000
determines a
drug's
therapeutic
effect; at this
point, the drug
is presumed to
have some
effect
Phase IV
Postmarketing
surveillance -
watching drug use
in public
therapeutic dose
personal
physician
anyone seeking
treatment from
their physician
watch drug's
long term
effects
Phase V
translational
research
no dosing none all reported use
research on data
collected
phase primary goal dose patient monitor
typical
number of
participants
notes

15. Informed consent form:
◦ Voluntary
◦ Explained in simple nontechnical language
◦ Translated in the native language of the subject
◦ Comprehensive information regarding the trials
Benefit of new therapy over existing ones
Alternative treatments available
◦ All possible adverse reactions
◦ Freedom to withdraw from the trial
at any time,
without giving any reason

16. Compensation in drug related injuries
◦ Mild and Severe
Patient Rights
◦ Confidentiality of data
◦ Right to withdraw
Collection procedures & amount of biological material taken
Compensation & Insurance claims
Sending bio-material abroad
Selection of Patients
Problem areas

17. Conclusion
Clinical trial is the scientific study of drugs in man.
Based on the results obtained from the animal experiments, the
mechanism of action, potential therapeutic application, approximate
dose range and possible toxicities are first established for a compound
under investigations.
These results are then translated in the humans in a cautious manner
that form the basis of clinical pharmacology which deals with Drug input,
Pharmacokinetics, Pharmacodyanamics, Pharmacogenetics,
Pharmacogenomics, Factors affecting Drug response and finally the
toxicity and side effects

18. Bibliography
1. M.N. Gosh, (2008) Fundamentals of Experimental Pharmacology,4th Edition,
Hilton and Company, Kolkata.
2. S.K. Kulkarni, (2012) Handbook of Experimental Pharmacology, 4th Edition,
Vallabh Prakashan, Delhi.
3. Breckenridge, A.M. (1980) Br. Med. J. 280,1303.
4. Greenwood, D.T. and Todd, A.H.(1977) In Clinical Trials.Johnson, F.N. and Johnson,
S., eds.,Blackwell Scientific Publications, Oxfords.
5. Guidelines for Clinical Trials on Pharmaceutical Products in India(2201) Published
by the Ministry of health and Family Welfare, Government of India, New Delhi.
6. Melmon, K.L. and Morrelli, H.F.(1978) Clinical Pharmacology: Basic Principles in
Therapeutics, 2nd Edition, Macmillan Publishing Company Inc. N.Y.

19. THANK YOU ALL
THANK
YOU ALL
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YOU ALL
THANK
YOU ALL