Pharmacology PPT

1. Dr. Chintan Doshi

2. What is a Clinical trial?
• prospective ethically designed investigation in It
human subjects to objectively
discover/verify/compare the results of two or more
therapeutic measures (drugs)
• A clinical trial is a planned experiment that involves
volunteers/patients
• Aim to compare the response to new treatment with
that of an existing one or placebo
• Clinical trial is just a part of New Drug Discovery
Process.

3. Why are clinical trials important?
• Clinical trials translate results of basic
scientific research into better ways to
prevent, diagnose, or treat disease
• The more people take part, the faster we can:
 Answer critical research questions
 Find better treatments and ways to prevent disease

4. Types of clinical trial
• Randomized
• Blinded or open label
• Prospective or retrospective
• Placebo
• Pilot study.
• Cross-over study.

5. Randomized Clinical Trials
• Subjects have equal chance to be assigned to one of
two or more groups just like tossing of coin.
– One group gets the most widely accepted treatment
(standard treatment)
– The other gets the new treatment being tested
– All groups are as alike as possible; removes the probability of
bias.

6. Randomisation
1
3
7
9
10
8
2 4
5
6
2
4
5 6
1
3
7
9 10
8 Control Group
Investigational group

7. Why is randomization important?
• So all groups are as alike as possible
• Provides the best way to prove the effectiveness of a
new agent or intervention

8. Open label trial Blinded clinical trial
Doctor and patient know
which drug is given
Single Blind: the patient
doesn’t know which treatment
he/she is getting
Double Blind: neither doctor
nor patient knows

9. Prospective Retrospective
Patients are enrolled for
the study before any
treatment begins
Past case records & other
statistical data are used for
analysis
Progress of patients is
monitored during course
of treatment
Investigator has to rely on
methods employed & data
available.

10. Placebo study
• Placebo
 It is an inert medicament given in the garb of
medicine.
It resembles the active drug in physical properties
but does not have any pharmacological activity.
• The new treatment is tested against a placebo.

11. Pilot Study
• A small study that helps to develop a bigger study.
• Advantage :
 to find out possible difficulties
 to help with design of the bigger, more pivotal study.

12. Cross-over study
• Two types of treatment are studied in the same
group.
• Before giving 1st treatment baseline observations are
made for certain period – “Run-in period”.
• When one treatment is over, before starting 2nd
treatment some time is allowed for the effect of
treatment to completely wash out – “Wash-out
period”.

13. • Advantages
No. of subjects required is less.
Minimizes chances of subject variation.
Cross over design
Standard Placebo Test
Placebo Test Standard
Test Standard Placebo
* A wash out period of a week between two weeks of
therapy
Group Week 1 Week 2 Week 3
1 Standard Placebo Test
2 Placebo Test Standarad
3 Test Standard placebo

14. Phase I
25-100
healthy volunteers; exception are cytotoxic
drug and antiretroviral drug.
Done by trained clinical pharmacologist
Non blinded or open labeled

15.  Determines
• SAFETY
• PHARMACOKINETICS
• PHARMACODYNAMICS
• DETERMINE MAXIMUM TOLERATED DOSE AND
ADVERSE EFFECTS OF THIS DOSE

16. Phase II
First time in patient with target disease
Requirements – phase I trial results & IRB
(Institutional review boards) approval
100-300 patients
Randomised & controlled, may be blinded
Carried out by clinicians

17. Determines
Therapeutic efficacy.
 Effective dose range
 Safety re-evalution
 Further Pharmacokinetic data

18. Phase III
• 1000-3000 patients
• Multicentric trial
• Double-blind randomized trials
• Large scale controlled trials
• Costly, difficult to organize

19. • Determines
How the new treatment compares with the
current standard or how it compares with placebo
Long term effectiveness & safety
• Then drug will be submitted to the relevant
regulatory authorities for licensing.

20. • It takes 5-7 years normally to complete phase 1, 2, 3
trials.
• On completion of three phases ‘NEW DRUG
APPLICATION’ is submitted to drug controlling authority.
• It includes complete detailed monographs of product,
results of the trial, the proposed name of this product,
and package insert.
• Then data are reviewed by drug controlling authorities. (
DCGI, FDA ).
• If acceptable then it can allow the drug to enter the
market with ‘NEW DRUG STATUS’.

21. Phase IV
 Post marketing survilance
To know rare and long-term adverse
effects
Special groups like children, pregnancy
etc can be tested

23. End point in clinical trial
 Defination : Objective measures use to assess
impact of intervention and prove or disprove a
hypothesis.
 Primary end point :
 Measures outcome that will answer the primary
question asked by trial.
 Secondary end point :
 ask other relevant question about the study
 e.g. reduction in cost

24. How Are Patients’ Rights
Protected?
 Ethical and legal codes that govern medical practice
also apply to clinical trials
 Approval of protocol by ethics committee.
 Informed consent
 Review boards
Scientific review
Institutional review boards (IRBs)
Data safety and monitoring boards

25. INFORMED CONSENT
• Informed Consent: A Process by which a
subject voluntarily confirms his or her
willingness to participate in a particular trial,
after having been informed of all aspects of
the trial that are relevant to the subject’s
decision to participate.

26. BIAS
• Definition: Bias is a systematic error in estimation
which is not reduced by increasing the study sample
size
 To avoid BIAS Clinical trial should be ;
 CONTROLLED [comparison of A with B, rather than study
of A alone]
 RANDOMISED[ assignment of subject to A or B on
randomly]
 DOUBLE BLIND [ neither subject nor assessor knows
whether A or B is being used.]

27.  TYPES OF ERRORS
• TYPE-1: occur if a difference is found between A and
B when none actually exists [false positive]
• TYPE-2: occurs if no difference is found though A and
B do actually differ [false negative]

28. Potential drug candidate
Preclinical testing
IND application form
Clinical trial phases 1 - 3
New drug application
Post marketing surveillance

29. Problem areas
• 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
• Selection of Patients

30. Drug discovery can cost up to 800
million to a billion dollars !