Clinical trials involve several phases of testing new medical interventions in human subjects to generate safety and efficacy data. Phase 0 trials involve microdosing to determine pharmacokinetic and pharmacodynamic properties. Phase I trials use small patient groups to determine maximum tolerated dose. Phase II trials screen for activity, safety and feasibility in larger patient groups. Phase III trials are large randomized controlled trials that compare new treatments to standard treatments. Phase IV trials monitor long-term safety and effectiveness if the treatment is approved. The goal is to progress from exploratory to definitive assessment through each phase to provide evidence for approval or non-approval of the new medical intervention.

1. By
K.Sai sudha

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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5. Phases of clinical trials
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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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10. Phase I Standard 3 + 3 Design
Dose
DLT
3 pts
3 pts
Recommended dose
3 pts
3 pts
3 pts
Starting dose
+
3 pts
DLT
3 pts

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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16. Summary of various phases
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17.  Positive trial
 Non-inferior trial
 Inconclusive trial
 Negative trial
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