Pharmacovigilance, its importance, objectives and assessment

Pharmacovigilance, its importance, objectives and assessment

1. PH PS OP /// Scorecard 2022 & Review process 1 SYED KASHIF FAYYAZ OBS Pharma (Pvt.) Ltd., Lahore PHARMAC OVIGILANC E

2. Adverse Drug Reactions (ADR s ) Definition of an ADR is often confused with that of an adverse drug event (ADE) The WHO defines an ADE as “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” The WHO defines an ADR as “A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” 2

3. In simple words An ADR in a patient is an adverse outcome that is attributed to a suspected action of a drug, An ADE is an adverse outcome that occurs after the use of a drug, but which may or may not be linked to use of the drug. Therefore → All ADRs are ADEs, but that not all ADEs will be ADRs The meaning of ADR differs from the meaning of "side effect ", as this last expression might also imply that the effects can be beneficial. 3

4. Extended Rawlins-Thompson Classification of ADR s 4

5. DOTs system of ADR classification 5

6. Economic impact The cost to the country of ADRs may exceed the cost of the medications themselves 30-60 % of ADRs may be preventable 6

7. Possible causes of ADR s Intrinsic Idiosyncrasy - the proposed mechanism of most idiosyncratic drug reactions is immune-mediated toxicity.  Mutagenicity - the capability of a substance to induce a genetic mutation in the base-pair sequence of DNA. Carcinogenicity - the ability of a substance to cause cancer. Teratogenicity - the ability of a substance to cause defects in a developing fetus. Extrinsic Adulterations Contamination Underlying medical conditions Interactions Wrong use 7

8. Before drugs become available to the patients, they are subjected to rigorous clinical studies. However, some adverse drug reactions (ADRs) are often detected ONLY after marketing. Pre-clinical Research Post-marketing Surveillance in real life patients 8

9. Limitations of Clinical trials Number of patients is limited Narrow population: Specific age and sex Narrow indications: only those having the specific disease studied Short duration: often no longer than a few weeks 9

10. Required sample size for detecting a rare ADR 10

11. Pharmacovigilance Pharmaco (Greek) : Drug Vigilance (Latin): to keep awake or alert to keep watch the process of paying close and continuous attention 11

12. Pharmacovigilance “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems” 12

13. Objectives 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; Detect problems related to the use of medicines and communicate the findings in a timely manner; Contribute to the assessment of benefit, harm, effectiveness and risk of medicines, leading to the prevention of harm and maximization of benefit; Encourage the safe, rational and more effective (including cost-effective) use of medicines; and Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public 13

14. Why do we need PV? Reason 1: Insufficient evidence of safety Animal experiments Clinical trials prior to marketing Reason 2: Dying from a disease may be inevitable, dying from a medicine is unacceptable (WHO,2005) Reason 3: ADRs are expensive 14

15. A lesson from the History 15

16. Thalidomide tragedy Biggest man‐made medical disaster ever Thalidomide was released in the late 1950's as a non-addictive, non-barbiturate sedative by the German pharmaceutical company, Chemie‐Grunenthal It was very effective and quickly discovered to also be an effective anti‐emetic and used to treat morning sickness in pregnant women . It was marketed and distributed in 46 countries around the world using different names. It became one of the world's largest selling drugs, and was marketed heavily and advertised as completely safe right up until it was eventually banned in November, 1961 . Sample packets of the drug were given out to physicians to distribute freely to patients suffering from morning sickness 16

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18. Soon after its release, reports surfaced of patients developing peripheral neuropathy after consuming thalidomide. Reports of occurrences of severe birth defects affecting multiple body systems were also coming to light, that initially were not linked to, or were denied to be due to thalidomide. In 1961, thalidomide was confirmed by two independent clinicians, Lenz in Germany and McBride in Australia, to be the cause of the largest man‐made medical disaster in history with huge numbers (over 10,000) of severe birth defects in children Many babies with these malformations are likely to have died in utero and been miscarried or stillborn. The true numbers of babies affected by thalidomide will likely never be known. 18

19. Pair of artificial arms for a child, Roehampton, England, 1964 19

20. Some Examples of Drug withdrawn from market due to safety reasons Drugs Adverse effects Thalidomide Phocomelia Practolol Sclerosing Peritonitis Fenformin Lactic acidosis Rofecoxib Cardiovascular events Veralipride Anxiety and depression, Movement disorders Troglitazone Hepatitis Rosiglitazone Cardiovascular events 20

21. ISOTAB Tragedy in PAKISTAN 21

22. PV cycle 22

23. Actions taken from the PV findings Restriction in use Changes in the specified dose of the medicine Introduction of specific warnings in the product information Changing the legal status of a medicine, e.g., from over-the-counter to prescription only Product recall: In rare cases, removal of the medicine from the market, if the risks of a medicine are found to outweigh the benefits 23

24. International collaboration in the field of pharmacovigilance WHO runs the Uppsala Monitoring Centre started in 1968, moved to Uppsala Sweden in 1978 European Union runs the European Medicines Evaluation Agency (EMEA) United States, the FDA is responsible for monitoring post-marketing studies . MedWatch: The FDA Safety Information and Adverse Event Reporting Program. In Pakistan → Pakistan National Pharmacovigilance Center, Drug Regulatory Authority Pakistan 24

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26. Why is it important for countries to support their own PV programs? Citizens may have unique traditions and diets influencing reactions to medications ADRs may be associated with traditional or herbal remedies unique to each country In some cases, ADRs to certain drugs may only occur in particular ethnic groups Alternate brands of therapy may be imported or manufactured & differ in ingredients or production processes 26

27. Pharmacovigilance System in Pakistan 27 National Pharmacovigilance Centre (NPC) is working under the Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP) that collects reports of adverse events from healthcare professionals, Patients, Provincial Pharmacovigilance Centres , Public Health Programmes and Registration holders of therapeutic goods. Drug Regulatory Authority of Pakistan Ministry of National Health Services, Regulations & Coordination

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29. 29 Pharmacovigilance System in Pakistan

30. Reporting Adverse Events National Pharmacovigilance Centre, DRAP collects reports of suspected Adverse Events associated with the use of therapeutic products. Anyone can report a suspected adverse events. DRAP has enabled both electronic and manual systems for collection of reports of suspected adverse events 30 Med Vigilance E Reporting Med Safety Mobile App Yellow Reporting Form/ Suspected Adverse Drug Reaction Reporting Form

31. What should be reported? All suspected reactions including minor ones. All serious, unexpected, unusual ADRs. Change in frequency of a given reaction. All suspected drug-drug, drug-food, drug food supplements interactions. ADRs associated with drug withdrawal. ADRs due to medication errors. ADRs due to lack of efficacy or suspected pharmaceutical defect. 31

32. Who can report? Patients, patients relatives or patients carers Health care professionals Physicians Dentists Pharmacists Nurses Manufacturers Authorities 32

33. Causality ASSESSMENT How likely is this medication the cause of this problem in this particular patient? 33

34. The Naranjo algorithm 34 Total scores range from -4 to +13; the reaction is considered definite if the score is 9 or higher, probable if 5 to 8, possible if 1 to 4, and doubtful if 0 or less.