CLINICAL TRIALS – PHASE IV

PHASE IV
 Phase IV are post marketing studies and provide
basis for continued marketing. They may also
provide information to amend the package inserts
in terms of safety, precautions etc.
 Phase IV studies provide additional data on safety
which may lead to safer use of the drug
OBJECTIVE
 Determine the behaviour of the drug when used in
real life situation without the dietary control and the
control of commonly used items like nicotine and
alcohol.
 Determine if at all any missed rare adverse reaction
or adverse reaction coming in late.
 To evaluate the action of the drug in a situation
missed dosage or “over dosage”.
Regulatory Requirements
 Permission of Drugs Controller General (India)
 Can be obtained for these studies
 The Drugs and Cosmetics Act does not specify that such
a permission is required.
 Approval of the Institute Review Board
 Itis being hotly debated
 So far DCGI has not demanded IRB clearance for these
studies.
STUDY POPULATION
 May be conducted in clinics, hospitals and private
practice
 All patients with target disorder, but with greater
heterogeneity
 Include all types of patients for whom the drug may
be indicated
I/E CRITERIA
 Inclusion criteria to specify
 Gender, age range of patients
 Diagnosis to conform with target indication
 Patients giving informed consent

 Exclusion criteria to specify

 Co-morbidities
 Pregnancy, lactation
 Physiological functions
CATEGORIES of TRIALS
Marketing oriented including seeding trials
II. Trials to learn more about the drug
 Mechanism of action

 Fine point of safety profile

 Quality of life

 Questions which may have come up during Phase I to

Phase III
III.Post marketing surveillance study
Difference between Trials
Parameter Phase I to III Phase IV

Medical Clinic/Hospital Clinical Practise

Environment
Patient Restricted Unrestricted
Population
Sample Size Few Many
Investigator Type Research Practise
Oriented Oriented
Protocol Fixed Flexible
Concomitant Rare Allowed
Therapy
Patient Mostly Objective Often Subjective
Evaluation
Design of Trial Formal Structure Less rigid
Sponsor’s Goal Efficacy and Marketing
Safety advantage
Pharmacoepidemiology
 The goal of pharmacoepidemiology is to discover
previously unknown ADRs and to estimate their
frequency

 Addresses that what cannot be addressed in Phase I

- III CTs