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  It is 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 Environment Clinic/Hospital Clinical Practise Patient Population RestrictedUnrestricted Sample Size FewMany Investigator Type Research Oriented Practise Oriented ProtocolFixedFlexible Concomitant Therapy RareAllowed Patient Evaluation Mostly Objective Often Subjective Design of Trial Formal Structure Less rigid Sponsor’s Goal Efficacy and Safety Marketing 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