Clinical trials are important for translating basic scientific research into better treatments and prevention strategies for diseases. They involve testing investigational treatments on human subjects through a rigorous multi-step process. The document outlines the key aspects of clinical trials, including: 1) Clinical trials are designed to objectively compare investigational treatments to existing standard treatments or placebos. Randomization and blinding help reduce bias. 2) Data from clinical trials help answer critical research questions faster and find better treatments. Phases I-IV assess safety, efficacy, and long-term outcomes of new drugs. 3) Informed consent, ethics review boards, and data monitoring protect patients' rights and welfare during clinical trials. Randomization, blind

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
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10
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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 !