By K.Sai sudha

Definition of clinical trial

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• 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.

Treatment Trials

Prevention Trials

Diagnostic Trials

Screening Trials

Quality of Life Trials

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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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Phases of clinical trials

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PHASE 0 CLINICAL TRIALS: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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ADVANTAGES and LIMITATIONS:

ADVANTAGES:ADVANTAGES:

Microdose is used so, ADE are lessShort durationInexpensiveUseful 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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•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

Phase I trials

3 pts

Dose

3 pts

3 pts

3 pts

3 pts

3 ptsRecommended dose

DLT

Starting dose

3 pts++ DLT

Phase I Standard 3 + 3 Design

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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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Phase IIa

EARLY PHASE

Pilot clinical trials

20-200 PATIENTS

SINGLE BLIND comparison

with a standard drug

Phase IIb

LATE PHASE

Pivotal clinical trials

50-300 PATIENTS

DOUBLE BLIND compared with

a placebo or standard drug

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• 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 III

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• Phase IIIa

• Prior to NDA

• Generates data on safety and

efficacy in both controlled

and uncontrolled trials.

• Provides much of information

for the package insert

• Phase IIIb

• After the NDA but prior to the approval and

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.

Phase III

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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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Summary of various phases

Positive trial

Non-inferior trial

Inconclusive trial

Negative trial

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