Pharmacovigilance
- 3. WHAT IS PHARMACOVIGILANCE ? Pharmaco + Vigilance Derived from greek Pharmaco – Medicine Vigilare – To watch The process of paying close and continuous attention
- 4. DEFINITION Pharmacovigilance is the science and activities relating to the Detection Assessment Understanding and Prevention of adverse drug reaction or any other possible adverse drug related problems “ Recently, its concerns have been widened to include herbals, traditional and complementary medicines, blood products, biologicals, medical devices and vaccines” WHO 2002
- 5. AIMS OF PHARMACOVIGILANCE • Improve patient care and safety in relation to the use of medicines, and all medical and paramedical interventions • Improve public health and safety in relation to the use of medicines • Contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use • Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public.
- 6. NEED OF PHARMACOVIGILANCE Reason 1: Humanitarian concern • Insufficient evidence of safety from clinical trials • Tests in animals are insufficient to predict human safety • Safety profile in special groups (elderly, parous women,childern) inadequate / Incomplete Reason 2: Ethics Known to cause harm and not informing the patient is unethical
- 7. Reason 3: Medicines are supposed to save lives ‘Dying from a disease is sometimes unavoidable; dying from a medicine is unacceptable’ Lepakhin V. Geneva 2005 ADRs were 4th-6th commonest cause of death in the US in 1994 Lazarou et al, 1998
- 8. Reason 4: ADRs are expensive !! • Cost of drug related morbidity and mortality exceeded $177.4 billion in 2000 (Ernst FR & Grizzle AJ, 2001: J American Pharm. Assoc). • ADR related cost exceeds the cost of the medications themselves. Reason 5: Promoting rational use of medicines and adherence Reason 6: Ensuring public confidence
- 9. EVOLUTION OF PHARMACOVIGILANCE 1934-1960 Period of Drug Explosion
- 10. USA Diethyleneglycol (DEG) Mistakenly used to solubilize Sulphanilamide 107 died
- 11. The Thalidomide Disaster 1956 Thalidomide launched in market 1959-61 Reports of foetal abnormalities (20,000 cases ) (maximum in Germany)
- 12. 1962 USA revised law requiring to prove safety and efficacy before issuing marketing authorization 1963 British committee on safety of drug monitoring 1964 UK starts the “YELLOW CARDS” system 1964-65 National ADR reporting system UK, Australia, New Zeland, Canada, West Germany, Sweden 1978 WHO center moved from GENEVA to UPPSALA
- 13. THALIDOMIDE (1961) Congenital limb defects BENOXAPROFEN (1982) Hepatotoxicity PHENFORMIN (1982) Lactic acidosis FENFLURAMINE (1997) Heart-valve abnormalities ASTEMIZOLE Many drug interactions PHENYLPROPANOLAMINE(2000) Haemorragic stroke CERIVASTATIN Rhabdomyolysis CISAPRIDE Cardiac arrythmias ROFECOXIB (2004) Cardiovascular events VALDECOXIB (2005) Cardiovascular events, TEGASEROD (2007) Cardiovascular events CLOBUTINOL (2007) Cardiac arrhythmia DRUGS WITHDRAWN FROM MARKET
- 14. TERMINOLOGIES IN PV Adverse Drug Reaction (ADR) A response to a medicine which is noxious and unintended, and which occurs at doses normally used in man Adverse Drug Event (ADE) Any untoward medical occurrence that may present during treatment with a medicine but which does not necessarily have a causal relationship with this treatment Side Effects Any unintended effect of a pharmaceutical product occurring at doses normally used by a patient which is related to the pharmacological properties of the drug
- 15. Unexpected Adverse Drug Reaction An adverse reaction, the nature or severity of which is not consistent with domestic labelling or market authorisation, or expected from characteristics of the drug Serious Adverse Drug Event / Reaction Untoward medical occurrence that at any dose: • Results in death • Requires inpatient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability / incapacity • Is life-threatening
- 16. CLASSIFICATION OF ADRS (RAWLIN AND THOMPSON CLASSIFICATION) • Type A - Dose related – expected – extension of pharmacological effects Salbutamol and tachycardia • Type B - Non dose related – bizarre – more serious Penicillin rash • Type C - Dose and time related – related to cumulative drug use NSAID’s induced Nephropathy • Type D - Delayed effects – carcinogenesis and teratogenicity Thalidomide and phocomelia • Type E - End-of-use - due to withdrawal Addisonian crisis after steroid withdrawal • Type F - Failure of therapy Prescription, diagnosis, missed selection of the medicine or doses.
- 17. SEVERITY OF ADR’S • Minor: No need of therapy, antidote, or hospitalization • Moderate Requires drug change , specific treatment, hospitalization • Severe Potentially life threatening; permanent damage, and prolonged hospitalization. • Lethal Directly or indirectly lead to death
- 18. IS IT AN ADR? • Take a Proper History and do a relevant examination • Establish time relationship : Some response are quick / delayed. Logical relation between initiation of therapy and appearance of ADR • Do a thorough physical examination with appropriate laboratory investigations • Effect of Dechallenge and Rechallenge should be determined • Literature search of the Medicine which caused the ADR
- 20. DIFFERENT SCALES FOR CAUSALITY ASSESSMENT • Naranjo’s algorithm • Kartch Lasagna`s algorithm • WHO probability scale • Spanish quantitative imputation scale • Kramer's scale • Jones scale • European ABO system • Bayesian system
- 23. INTERPRETATION TO TOTAL s • Total scores of 9 or more mean that ADR is highly probable • Scores from 5 to 8 mean that ADR is probable. • Scores from 1 to 4 that ADR is possible. • Scores of zero or less mean that ADR is doubtful
- 24. PHARMACOVIGILANCE PROCESS 1. Detecting and Reporting an ADR ADR form is filled out with the patient and reaction details in the prescribed format • Spontaneous reporting • Mandatory reporting
- 25. Spontaneous reporting • Most common form of ADR reporting • Healthcare professionals identify and report any suspected adverse drug reaction to their National Pharmacovigilance Centers Mandatory reporting • Manufacturers are required to submit reports they receive from healthcare providers to the National Authority, in the form of a PSUR (Periodic Safety Update Report) • A regulatory document prepared by the Marketing Authorisation Holder & submitted to the Agency
- 26. COMPARATIVE OBSERVATIONAL STUDIES • Cross sectional survey • Case control study • Cohort studies • Large safety trial • Drug utilization study ACTIVE SURVEILLANCE • Site surveillance (hospitals, pharmacies, nursing homes etc.) • Focused ADR monitoring of drugs • Prescription event monitoring • Disease registries from Public health Programme OTHER METHODS FOR COLLECTING ADR
- 27. WHO CAN REPORT AN ADR ManufacturerDentistPharmacist Doctor Nurse Others
- 28. STAKEHOLDERS IN PV • Government • Industry • Hospitals and academia • Medical and pharmaceutical associations • Poisons information centres • Health professionals • Patients • Consumers • Media • WHO
- 29. FACTORS TO BE REPORTED • Report all suspected reactions including minor ones in case of new drugs • For established or well known drugs - All serious, unexpected, unusual ADRs • ADRs to generics not seen with innovator products • ADRs to traditional medicines • All suspected drug-drug, drug-food, drug-food supplement interactions • ADRs associated with drug withdrawals • ADRs due to medication errors • ADRs due to lack of efficacy or suspected pharmaceutical defects
- 30. HOW TO REPORT Different forms have been developed for reporting ADR’s: • MEDWATCH by FDA • YELLOW CARD • Submitting forms to the nearest national Pharmacovigilance centers
- 31. WHEN TO REPORT Timeline of reporting an ADR • By the sponsor to Licensing Authority – 14 calendar days • Investigator to the sponsor within 24 hours • Investigator to the Ethics Committee within 7 working days
- 32. WHERE TO REPORT • WHO & UMC • Uppsala Monitoring Centre (UMC) - is responsible for the management of the WHO program for International Drug Monitoring • Computer software for case report management designed to suit the needs of National Centers (Vigiflow) FUNCTIONS OF UMC • To co-ordinate the WHO program for international drug monitoring and its member countries • To collect, assess and communicate information from member countries about the benefits, harms and risks of drugs and other substances used in medicine to improve patient therapy and public health worldwide • To collaborate with member countries in the development and practice of the science of pharmacovigilance
- 33. Pharmacovigilance in UK • Yellow Card Scheme • ADROIT – Adverse Drug Reactions Online Information Tracking system. Pharmacovigilance in USA • MEDWATCH • MEDWATCH 3500 form / FDA form 3500 Pharmacovigilance in India • Central Drugs Standard Control Association – DGHS, Ministry of Health & Family Welfare • Legislative requirements of PV in India – Schedule Y of the drugs & cosmetic act 1945
- 34. INDIAN SCENARIO • No Formal PVG system initially - sourced their safety assessment of drugs on data derived US, EUROPE & JAPANESE MARKETS. • 1986 - Formal PVG activities were initiated • 1997 – India joined the Adverse Drug Reaction Monitoring Programme of WHO. • 2004 –2008 National Pharmacovigilance Prog. (2 Zonal, 5 Regional, 24 Peripheral Centers) • Due to some technical difficulties the NPP had to be closed in 2008 • It was again resurrected as the PHARMACOVIGILANCE PROGRAMME OF INDIA (PvPI) In 14/07/2010 @ AIIMS
- 35. For more effective implimentation of the programme the center was shifted from AIIMS to INDIAN PHARMACOPOEIA COMMISSION, GHAZIABAD on 15/04/2011.
- 36. AIMS & OBJECTIVES Aim: • To ensure that the benefits of use of medicine outweighs the risks and thus safeguard the health of the Indian population
- 37. Objectives : • To monitor Adverse Drug Reactions (ADRs) in Indian population • To create awareness amongst health care professionals about the importance of ADR reporting in India • To monitor benefit-risk profile of medicines • Generate independent, evidence based recommendations on the safety of medicines • Support the CDSCO for formulating safety related regulatory decisions for medicines • Communicate findings with all key stakeholders • Create a national centre of excellence at par with global drug safety monitoring standards
- 39. A. Patient information B. Suspected adverse reaction • Date when started and recovered • Reaction description C. Suspected medication D. Reporters information
- 41. NUMBER OF ADR MONITORING CENTRES • SOUTH ZONE-25 AMC’S • NORTH ZONE-28 AMC’S • WEST ZONE-20 AMC’S • EAST ZONE-17 AMC’S.
Editor's Notes
- #30: ascending radiculomyeloencephalopathy,