Pv overview (2)


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Pv overview (2)

  1. 1. Pharmakon = drug Vigilare = to keep watch  Development of science and regulation in drug safety.  Safety of drugs under the practical conditions of clinical use  Identifying new information about hazards associated with medicines, preventing harm to patients Pharmacovigilance: science and activities relating to the detection, assessment, understanding and prevention of adverse drug reactions
  2. 2.  Thalidomide tragedy (1961-62): The greatest of all drug disasters.  Thalidomide: introduced and welcomed as a safe and effective drug for the treatment of nausea and vomiting in early pregnancy.  Tragically the drug proved to be a potent human teratogen that caused major birth defects in an estimated 10,000 children  Phocomelia was a characteristic feature
  3. 3.  improve patient care and safety  improve public health and safety  contribute to the assessment of benefit, harm, effectiveness and risk of medicines  promote understanding, education and clinical training
  4. 4.  Insufficient evidence of safety from clinical trials  Animal experiments  Phase 1 – 3 studies prior to marketing authorization Medicines are supposed to save lives!
  5. 5. Phase IV Post-approval studies to determine specific safety issues Clinical development of medicines Animal experiments for acute toxicity, organ damage, dose dependence, metabolism, kinetics, carcinogenicity, mutagenicity/teratogenicity Preclinical Animal Experiments Phase I Phase II Development Post Registration Phase III Phase IV Post-approval Spontaneous ReportingRegistration Phase I 20 – 50 healthy volunteers to gather preliminary data Phase II 150 – 350 subjects with disease - to determine safety and dosage recommendations Phase III 250 – 4000 more varied patient groups – to determine short-term safety and efficacy
  6. 6.  Standard conditions  limited group of selected patients  narrow population: age and sex specific  narrow indications: only the specific disease studied  short duration: often no longer than a few weeks
  7. 7. AE: Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment ADR: A noxious and unintended response to a drug at normal doses for prophylaxis, diagnosis or therapy of disease ADEs ADRs Diseases Genetics Other Drugs Environment Diet Other factors
  8. 8.  Type A Effects (“Augmented”): common, dose dependent & predictable  Type B Effects (“Bizzare”): rare, dose independent & unpredictable  Type C Effects (“Chronic”): after long term therapy, no time relationship  Type D Effects (“Delayed”): may be presented years after  Type E Effects (“End of treatment”): Absence of drug after withdrawal
  9. 9. ADRs that is either: • life-threatening, • fatal, • cause of prolong hospital admission, • cause persistent disability ADR, the nature or severity of which is not consistent with market authorization, or expected from the characteristics of the drug.
  10. 10. Association in timeLikelihood of a causal relationship between drug exposure and adverse events It is necessary to evaluate  Temporal relationship between drug use and event  Dechallenge and rechallenge information  Pharmacology (including current knowledge of nature and frequency of adverse reactions)  Medical or pharmacological plausibility (signs and symptoms, tests, pathological findings, mechanism)
  11. 11. Few assessment scales for causality evaluation include:  WHO probability scale  Naranjo scale  Karch and Lasagna scale  Jones scale WHO probability scale: Certain: positve dechallenge & positve rechallenge Probable: positve dechallenge & negative rechallenge Possible: temporal relationship Unlikely: disease or drug provide plausible explanations Unclassified: more data needed (under assessment) Unclassifiable: data cannot be verified
  12. 12. NARANJO's ALGORITHM question Yes No Don't know Are there previous conclusion reports on this reaction? +1 0 0 Did the adverse event appear after the suspect drug was administered? +2 -1 0 Did theARimprove when the drug was discontinued or a specific antagonist was administered? +1 0 0 Did theARreappear when drug was readministered? +2 -1 0 Are there alternate causes [other than the drug] that could solely have caused the reaction? -1 +2 0 Did the reaction reappear when a placebo was given? -1 +1 0 Was the drug detected in the blood [or other fluids] in a concentration known to be toxic? +1 0 0 Was the reaction more severe when the dose was increased, or less severe when the dose was decreased? +1 0 0 Did the patient have a similar reaction to the same or similar drugs in any previous exposure? +1 0 0 Was the adverse event confirmed by objective evidence? +1 0 0 > 9 = definite ADR 5-8 = probable ADR 1-4 = possible ADR 0 = doubtful ADR
  13. 13. Signal: reported information on a possible relationship between an adverse event and a drug, unknown or incompletely documented previously Usually more than a single report is required to generate a signal Data mining pharmacovigilance databases - become increasingly popular with the availability of extensive data sources and inexpensive computing resources
  14. 14. New drug: Any drug product that has not been marketed for more than five years PSUR: A report containing information collected by marketing authorisation holders through pharmacovigilance activities. It is usually required by regulatory authorities for drugs that have not been marketed for more than five years
  15. 15.  Spontaneous reporting: healthcare professionals (and in some countries consumers)  Aggregate Reporting: compilation of safety data of drug over a prolonged period of time - PSUR  Expedited Reporting: serious and unlabelled event Within clinical trials such a cases is referred to as a SUSAR (a Suspected Unexpected Serious Adverse Reaction)  Clinical Trial Reporting: safety information from clinical studies
  16. 16. Patient-HW Suspicion of ADR PV Unit/ Coordinator hand delivery Reporting ADR PV Unit/MoH HQ fax - mail courier Analyze ADR & submit to WHO/UMC database Analyze global ADRs Web upload Sharing the findings
  17. 17. • India – Central Drugs Standard Control Organization (CDSCO) • UK – Medicines and Healthcare Products Regulatory Agency (MHRA) • USA – Food and Drug Administration (US FDA) • Europe - The European Medicines Agency (EMEA) • Japan - Ministry of Health, Labor and Welfare (MHLW) • Australia – Therapeutic Goods Administration • Canada – Heath Canada • Switzerland - Swiss Agency for Therapeutic Products
  18. 18.  EudraVigilence – data processing network for reporting and evaluating suspected ADRs in European Economic Area  WHO- Uppsala Monitoring Centre (WHO-UMC) in Sweden – Established in 1978 – Coordination of the WHO programme for International Drug Monitoring – Collection, processing of data, Education, Research
  19. 19.  Increased awareness and interest amongst doctors and pharmacists to report ADRs  More hospitals and companies using on-line reporting system – less hassle than submitting hard copy reports  Increasing involvement by hospital pharmacists in pharmacovigilance – during clinical ward rounds and when counseling patients
  20. 20.  Increasing number of clinical trials being conducted especially in Singapore, Thailand and Malaysia  GCP training for investigators served to increase awareness of SAE and ADR reporting amongst health care professionals and the industry
  21. 21.  Generic Substitution  Increased self medication  Increased use of herbal medicines outside traditional culture of use  Biosimilars  Widespread Counterfeiting  Illegal sale on internet