Phase-IV Clinical trials

Dr.Pratibha Nadig.M.D.
Assoc.Professor
ICRI,Bangalore
 Phase IV Clinical trials
• Studies performed after marketing
of the pharmaceutical product.

• Other than the routine

surveillance studies
 Phase IV Clinical trials

• Carried out on the basis of product

characteristics on which marketing
authorization was granted.

• Required by the licencing

authorities for optimising the drug
use
 Phase-IV trials
• Objectives of the trial

• The pre-requisites

• Ethical guidelines

• Regulatory requirements

• Conduct of the trial

 Phase-IV trials
• Clinical trial design

• Types of studies

• Outcome

• Limitations
 Objectives


Conform the efficacy and safety
profile in large populations during
practice


Detect the unknown adverse drug
reaction/s

 Evaluation of over-dosage and

treatments


Identifications of new indications
 Objectives

Evaluation of new formulations,
dosages, durations of treatment

 Evaluation of different age groups

and other types of patients


Cost effectiveness
Pharmacoeconomics
 Prerequisites

• NDA approval

• Ethical approval for

selected studies
 Ethical considerations

IRB approval & IC are required

• if the study requires follow ups
and investigations which are not
routinely carried out
• in case of drugs which could lead to
potential inconvenience or harm
• in cases of new formulations,new
dosage forms, newer indications and
fixed dose combinations
 Drivers of Phase IV studies
• Commercial

• Academic

• Regulatory PMC,

• Efficacy

• Safety
 Regulatory requirements
• SAFETY
e.g: yellow card system in UK

• NEW INDICATIONS
Change of licence

• OTC from POM

Registrations for change in the class
 Conduct of the trial
• Post authorisation studies,post marketing
studies,post licencing studies.

• Site: Clinics and hospitals

• Players
Principal investigators-General
practitioners and Specialists
Participants patients-2000-10000+
 Clinical trial design
• OBSERVATIONAL STUDIES

• Cohort studies- Prospective uncontrolled

or controlled studies

• Case- control studies- Retrospective

 Types Phase-IV
• Pharmacovigilance

• Pharmacoeconomics

• Pharmacoepidemiology-Seeding studies

• Comparative studies

• Studies for new indications,dosage and

formulations
 Phamacovigilance
• Monitoring medicines to determine
unrecognised adverse effects or changes
in the patterns of their adverse effects
– yellow cards, signals from clinical trials

• Continuously assessing the risks and

benefits of medicines, taking action if
necessary to improve their safe use
– restricting use of a drug, withdrawing a drug
 Pharmacovigilance
Techniques
• Voluntary reporting

• Prescription event monitoring

• Medical record linkage:

• Population statistics
 Quality of life studies
Conducted for :
• Physical

• Social

• Psychological parameters

Eg: Captopril,Methyldopa, Propranolol in

hypertension
 Pharmacoeconomic studies
• Application of economic theory to drug
usage

• Comparison of cost- effectiveness of two

drug therapies

Eg: ondansetron and metaclopramide in the

prevention of acute emesis
 Seeding studies
• Uncontrolled cohort studies

• Questionnaire based study conducted by

the marketing department

• Large number of doctors required

• Aim –to change the prescribing pattern of

the physician
 Comparative studies
• Comparisons in the same therapeutic area but
different chemical class,e.g.Enalapril and
Propranolol

• Same class Nifedipine and Amlodipine

• Added beneficial end points over the existing

e.g: enalapril - left ventricular hypertrophy

• Different patient population Nitrendipine in

elderly patients for stroke
 New Indications
• Aspirin as anti-platelet agent

• Metformin in polycystic ovarian disease

• Propranolol in migraine
 New dosage forms

• E.g.Sustained release forms of Diclofenac

 New formulations

• Change in fluorocarbons as propellants in

metered dose inhalers
Change of status PMOs to
OTCs

• E.g.Paracetamol
• Extensive safety data to be generated
 Outcome of Phase-IV
• Safety profile; Signals of adverse reaction

• Confirm the efficacy and comparisons in

overall tolerability and QOL

• Efficacy in larger population for a longer

time

• Generalisation
 Outcome of Phase-IV
• Newer indications for existing drugs

• Newer formulations

• New dosage forms

• Arrival at the best treatment for the

patient population
Thank you