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.
Quality of Life Trials
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
FDA reviewers will approve the application or find it either "approvable" or "not
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
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
a potential drug in humans.
ADVANTAGES and LIMITATIONS:
Microdose is used so, ADE are less
Useful in the discovery of endogenous biomarkers
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
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
• 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.
Pilot clinical trials
Pivotal clinical trials
SINGLE BLIND comparison
DOUBLE BLIND compared with
with a standard drug
a placebo or standard drug
• 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
• 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
• Period between submission and approval of
a regulatory dossier for marketing
• These may supplement or complete the
earlier trials or may be directed to Phase IV
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.