Post on 14-Nov-2014
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Phase-IV Clinical trialsPhase-IV Clinical trials
Dr.Pratibha Nadig.M.D.
Assoc.Professor
ICRI,Bangalore
Phase IV Clinical trialsPhase IV Clinical trials
• Studies performed after marketing of the pharmaceutical product.
• Other than the routine surveillance studies
Phase IV Clinical trialsPhase 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 trialsPhase-IV trials
• Objectives of the trial
• The pre-requisites
• Ethical guidelines
• Regulatory requirements • Conduct of the trial
Phase-IV trialsPhase-IV trials
• Clinical trial design
• Types of studies
• Outcome
• Limitations
ObjectivesObjectives
Conform the efficacy and safety Conform the efficacy and safety profile in large populations during profile in large populations during practice practice
Detect the unknown adverse drug Detect the unknown adverse drug reaction/sreaction/s
Evaluation of over-dosage and Evaluation of over-dosage and
treatmentstreatments
Identifications of new indicationsIdentifications of new indications
ObjectivesObjectives
Evaluation of new formulations, Evaluation of new formulations, dosages, durations of treatmentdosages, durations of treatment
Evaluation of different age groups Evaluation of different age groups and other types of patientsand other types of patients
Cost effectiveness Cost effectiveness
PharmacoeconomicsPharmacoeconomics
Prerequisites Prerequisites
• NDA approval NDA approval
• Ethical approval for Ethical approval for
selected studiesselected studies
Ethical considerationsEthical 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 studiesDrivers of Phase IV studies
• Commercial
• Academic • Regulatory PMC,
• Efficacy
• Safety
Regulatory requirementsRegulatory 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 trialConduct 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 designClinical trial design
• OBSERVATIONAL STUDIES
• Cohort studies- Prospective uncontrolled or controlled studies
• Case- control studies- Retrospective
Types Phase-IVTypes Phase-IV
• Pharmacovigilance
• Pharmacoeconomics
• Pharmacoepidemiology-Seeding studies
• Comparative studies
• Studies for new indications,dosage and formulations
PhamacovigilancePhamacovigilance
• 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
PharmacovigilancePharmacovigilance
Techniques • Voluntary reporting
• Prescription event monitoring
• Medical record linkage:
• Population statistics
Quality of life studiesQuality of life studies
Conducted for :• Physical
• Social
• Psychological parameters
Eg: Captopril,Methyldopa, Propranolol in hypertension
Pharmacoeconomic studiesPharmacoeconomic 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 studiesSeeding 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 studiesComparative 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 IndicationsNew Indications
• Aspirin as anti-platelet agent
• Metformin in polycystic ovarian disease
• Propranolol in migraine
New dosage formsNew dosage forms
• E.g.Sustained release forms of Diclofenac
New formulationsNew formulations
• Change in fluorocarbons as propellants in metered dose inhalers
Change of status PMOs to Change of status PMOs to OTCsOTCs
• E.g.Paracetamol
• Extensive safety data to be generated
Outcome of Phase-IVOutcome 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-IVOutcome of Phase-IV
• Newer indications for existing drugs
• Newer formulations
• New dosage forms
• Arrival at the best treatment for the patient population
Thank youThank you