Phase - Iv Dr Pratibha

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

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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

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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