based on clinical trials

1. Testing of drugs on
human volunteers
Presented by,
JEEVA RAJ JOSEPH
15KUSM6008
2ND M.Sc. M.B.

2. INTRODUCTION
Clinical trial is a systematic investigation in human subjects for
evaluating the safety and efficacy of any new drug.
It is conducted only when satisfactory information has been
gathered on the quality of the non-clinical safety and health
authority’s approval is granted.

3. Testing a drug
Laboratory tests- chemical tests or tests on cell cultures
Tests on animals
Human volunteers
Clinical trials
(FDA) Food & Drug Administration- approval or rejection

5. Laboratory phase
In vitro screening – the potential medicines are tested on cell
cultures, tissue cultures and isolated whole organs in the lab.
Many chemicals fail at this stage because they don’t work or are
toxic.

6. Animal Phase
Precedes human testing
in vivo screening
watching for toxic effects, side effects, addictions, cancerous tumors
or fetal deformities
Calculating the Therapeutic Index (TI)…. The difference between the
dosage that produces a Therapeutic Effect and the dosage that
produces a Toxic Effect

7. Human Testing
Phases of Clinical Trial
Phase I : First in volunteer 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

8. Why Participate in a
Clinical Trial?
People volunteer to participate in clinical trials for different
reasons. Some volunteer because they want to help advance
medical knowledge. Others have tried all available treatments
for their condition without success.

9. Who Can Participate?
• It's important to test medical products in the people they are meant to help.
In the past, most new drug testing had been done on white men. It's
important to test medical products in a wide variety of people because
drugs can work differently in people of various ages, races, ethnicity, and
gender. The FDA seeks to ensure that people from many different groups
are included in clinical trials.
• Trial guidelines, or eligibility requirements, are developed by the
researchers and usually include criteria for age, sex, type and stage of
disease, previous treatment history, and other medical conditions.

10. What Happens in a Clinical
Trial?
• Every clinical trial is carefully designed to answer certain research
questions. A trial plan called a protocol maps out what study procedures will
be done, by whom, and why. Products are often tested to see how they
compare to standard treatments or to no treatment. The FDA often provides
extensive technical assistance to researchers conducting clinical trials,
helping them design better trials that can characterize effects of a new
product more efficiently, while reducing risks to those participating in the
trials.

11. What Happens in a Clinical
Trial?
• The clinical trial team includes doctors and nurses, as well as other
health care professionals. This team checks the health of the participant
at the beginning of the trial and assesses whether that person is eligible
to participate. Those found to be eligible--and who agree to participate--
are given specific instructions, and then monitored and carefully
assessed during the trial and after it is completed.

12. What Are the Risks?
• Some treatments being studied can have unpleasant, or even serious, side
effects. Often these are temporary and end when the treatment is stopped.
Others, however, can be permanent.
• Some side effects appear during treatment, and others may not show up
until after the study is over. The risks depend on the treatment being
studied and the health of the people participating in the trial. All known
risks must be fully explained by the researchers before the trial begins. If
new risk information becomes available during the trial, participants must
be informed.

13. IND Application Filing
Once preclinical studies have indicated the safety and efficacy of a drug an IND
application has to be filed with the regulatory authorities
• For obtaining regulatory Approval for Phase I, phase II and Phase III clinical
evaluation.
• Contents of IND application
Preclinical Data (All data from animal studies)
Information on composition and source of drug
Chemical and manufacturing information
Proposed clinical plans and protocol
Ethical Committee Clearance

14. Phase I
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
Performed by clinical pharmacologists
Takes 3 – 6 months [ 70% success rate]

15. Phase I Human trials:
testing on volunteers
The (very few) chemicals
that pass the animal
testing stage move on to
the first human tests.
These are done on
healthy people. This
stage checks the safety
of the drug and looks for
side effects. Animal tests
continue, looking for any
long term effects.

16. Phase II
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
Compared with a standard drug
Assesses efficacy against a defined therapeutic endpoint
Establishes a dose & a dosage form for future trials
Takes 6 months to 2 years [ 35% success rate]

17. Phase II: Testing on patients
The first ill people to get the drug are the Phase II
volunteers.
This is where scientists can really begin to see if the
drug will be safe and effective.

18. Phase III
Large scale, Randomised, Controlled trials
Target population: 250 – 1000 patients
Performed by Clinicians in the hospital
Minimises errors of phases I and II
To establish efficacy of the drug against existing therapy in larger
number of patients, method of usage, & to collect safety data etc.
Takes a long time: up to 5 years [25% success]
To determine optimal dosage schedule for use in general

19. Subtypes :
Phase IIIA: to get sufficient and significant data.
Phase IIIB: allows patients to continue the treatment, Label
expansion, additional safety data.
Phase III B studies are known as "label expansion” to show the
drug works for additional types of patients/diseases beyond the
original use for which the drug was approved for marketing

20. Phase III: Final tests and
licensing
If all goes well with phase II the
trials move to phase III. Many
more people are given the new
drug. Some of the people in the
phase III trial will be given
dummy treatment so that
doctors can compare the effect
of the drug with already
available medicines or nothing
at all. By the end of a successful
phase III the drug company
submits its research to
government bodies to ask for a
licence to sell the drug.

21. Phase IV or Post marketing
Surveillance
No fixed duration / patient population
Starts immediately after marketing
Helps to detect
 rare ADRs
 Drug interactions
 Also new uses for drugs [Sometimes called Phase V]
Studies continue to collect data about effects in various populations &
side effects from long term use.
These are primarily observational or non- experimental in nature.

22. Even once a medicine has been licensed for use it is still watched
carefully for unexpected problems. These phase IV trials, where
doctors report on any side effects suffered by their patients,
continue as long as the medicine is used. Phase IV trials can
involve hundreds of thousands of people.
Sometimes the trials throw up unexpected problems - medicines
can even be withdrawn from use because serious problems
appear! A drug company may decide to develop a new drug to
replace the original one because it has fewer side effects. The
whole process begins again!
 Peninsula Medical School

23. NDA: New Drug
Application
NDA Refers to New Drug Application
Formal proposal for the FDA/DCGI to approve a new drug for sale
Sufficient evidences provided to FDA/DCGI to establish:
Drug is safe and effective.
Benefits outweigh the risks.
Proposed labeling is appropriate.
NDA contains all of the information gathered during preclinical to phase III
Can take 2-3 years for FDA to review

24. Conclusion
Clinical trial is a human experiment designed to study the efficacy and
safety of a new drug/intervention
Involves Phase 1-4 with specific objectives and end results
Application to Regulatory authority:
IND – Permission to conduct CT
NDA – Permission to Market New drug
Well designed and effectively executed clinical trials form the base of
therapeutic decisions