2. Definition of clinical trial
• Clinical trials are a set of tests in medical research and drug development that
generate safety and efficacy data for health interventions in human beings.
• Clinical trials are conducted only after satisfactory information has been
gathered on the quality of the nonclinical safety, and health authority/ethics
committee approval is granted in the country where approval of the drug or
device is sought.
• Clinical Trials are “real world” applications of the Scientific Method.
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3. Treatment Trials
Prevention Trials
Diagnostic Trials
Screening Trials
Quality of Life Trials
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4. 1. Preclinical (animal) testing.
2. An investigational new drug application (IND) outlines what the sponsor of a new
drug proposes for human testing in clinical trials.
3. Phase 1 studies
4. Phase 2 studies
5. Phase 3 studies
6. The pre-NDA period, just before a new drug application (NDA) is submitted.
7. Submission of an NDA is the formal step asking the FDA to consider a drug for
marketing approval.
FDA reviewers will approve the application or find it either "approvable" or "not
approvable."
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6. PHASE 0 CLINICAL TRIALS:
Human micro dosing studies
Exploratory IND studies by FDA
It is an important element of NEXT. It promises to shorten the timeline by upto 6-12
months
MICRO DOSE: Less than1/100 of the dose of a test substance calculated to yield
pharmacological effect of the test substance with a max dose of <100 micrograms
Patients Typically very small numbers of patients are involved.
These are very early studies of the pharmacodynamic and pharmacokinetic properties
of
a potential drug in humans.
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7. ADVANTAGES and LIMITATIONS:
ADVANTAGES:
Microdose is used so, ADE are less
Short duration
Inexpensive
Useful in the discovery of endogenous biomarkers
LIMITATIONS:
Limited use of agents having Non linear PKs
Agents having different kinetic characteristics between microdose and full dose are not
evaluated by phase 0 trials.
The laboratory parameters are very limited and expensive, researchers have to depend on
BA/BE labs.
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9. Phase I trials
•The aim of a Phase I trial is to determine the maximum tolerated dose (MTD) of
the new treatment. The MTD is found by escalating the treatment dose until the
dose-limiting toxicity (DLT) is reached.
•20-25 healthy volunteers
•Patients: Anticancer drugs, AIDS therapy
•Duration: 6-12 months
•No blinding
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11. Phase II
• First in patients
• Duration: 6 months to several years.
• It acts as a screening stage.
• To evaluate activity, safety and feasibility of the new treatment.
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12. Phase IIa
Phase IIb
EARLY PHASE
LATE PHASE
Pilot clinical trials
Pivotal clinical trials
20-200 PATIENTS
50-300 PATIENTS
SINGLE BLIND comparison
DOUBLE BLIND compared with
with a standard drug
a placebo or standard drug
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13. Phase III
• Large scale, Randomised, Controlled trials . Minimises errors of phases I and II.
• To compare the new treatment against a suitable comparator.
• Target population: several 100’s to 3000 patients. Takes a long time: up to 5 years
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14. Phase III
• Phase IIIa
• Phase IIIb
• Prior to NDA
• After the NDA but prior to the approval and
• Generates data on safety and
efficacy in both controlled
and uncontrolled trials.
• Provides much of information
for the package insert
launch.
• Period between submission and approval of
a regulatory dossier for marketing
authorization
• These may supplement or complete the
earlier trials or may be directed to Phase IV
trials.
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15. No fixed duration / patient population
Starts immediately after marketing
These are primarily observational or non- experimental in nature.
Helps to detect rare ADRs, Drug interactions
Also new uses for drugs [Sometimes called Phase V]
Harmful effects discovered may result in a drug being no longer sold, or
restricted to certain uses.
2010
2011
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