INTRODUCTORY PHARMACOVIGILANCE 2024.pptx

Pharmacovigilance refers to the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. It plays a crucial role in ensuring the safety of medications once they are on the market by continuously monitoring and analyzing side effects, particularly those that were not detected during clinical trials.

Key elements of pharmacovigilance include:

1. Adverse Drug Reaction (ADR) Reporting: Gathering reports from healthcare professionals, patients, and pharmaceutical companies regarding any negative side effects of medications.


2. Signal Detection: Identifying new risks associated with medicines through data analysis and pattern recognition.


3. Risk Management: Developing strategies to minimize the potential harm of medications based on identified risks.


4. Regulatory Oversight: Collaborating with health authorities to ensure proper safety measures are in place for medications on the market.


5. Public Health Protection: Ensuring that the benefits of medicines outweigh their risks to protect patient safety.



Pharmacovigilance is a critical aspect of post-marketing surveillance to safeguard patients and improve drug therapies.

1. Pharmacovigilance 2024 BY DR. ABDULLAHI RABIU ABUBAKAR (B. PHARM, MSc, MPH , MPSN, PhD ) 1

2. Introduction Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.

3. Introduction… Pharmacovigilance was introduced in 1960s following the thalidomides incidence. Thousands of babies were born without limbs by pregnant who mothers who consumed thalidomide to treat morning sickness. In 1963, the World Health Assembly adopted a resolution for rapid dissemination of information on ADRs. Later WHO Pilot Research Project for International Drug Monitoring in 1968.

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5. WHO PV program began with ten countries that already have their own PV systems. Reports were analyzed locally and then forwarded to the WHO database ( Vigibase ). WHO Centers for International Drug Monitoring is located in Uppsala, Sweden. The primary aim of PV is detection , assessment, understanding, prevention, and reporting ADRs to vigibase . Introduction …

6. Introduction … Aims of Pharmacovigilance 1. Patient Care To improve patient safety in relation to medicines, medical & para -medical interventions. 2. Public Health To improve public health & safety in relation to the use of medicines. 3. Risk Benefit & Assessment To contribute to the assessment of risk, benefit, and effectiveness of medicines.

7. Introduction … Aims of Pharmacovigilance … 4. Risk Communication To promote understanding of new ADR and effectively communicate to other health professionals, regulatory agencies & WHO. 5. To promote rational and safe use of medicines Health Workers Responsibilities Timely collection of data, recording and notification Appropriate assessments (data completeness, seriousness) Expedited and periodic reporting Creates appropriate structures for communication

8. Need of Pharmacovigilance Animal toxicology is often not a good predictor for human effects. Evidence of safety from clinical trials is insufficient due to limited size (phase 1-3 ), narrow population (age & sex specific), narrow indications (only specific disease), short duration. Sources of post-market data Spontaneous Adverse Reaction reports Periodic Safety Update reports Registries Epidemiologic studies (sometimes) Phase IV clinical trials (PMS, rarely )

9. Adverse Drug Reaction (ADR) According to WHO (1972) ADR is 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.

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11. Classification of ADRs ADR is classified based on the following: 1. Type of reaction: Type A Type B Type C Type D Type E Type F 2. Onset of event : i. Acute (<60 minutes) ii. Sub-acute (1-24 hrs) iii. Latent (>2 days) 3. Severity : Minor, Moderate, Severe, Lethal ADRs.

12. ADRs Based on Types of Reactions A ugmented (Dose Related) B izzare (Non-Dose Related) C hronic (Dose Related and Time Related) D elayed (Time Related) E nd of Use (Withdrawal) F ailure (Unexpected Failure of Therapy)

13. A ugmented (Dose Related) Features Common Related to the pharmacologic action of the drug – exaggerated pharmacologic response Predictable Low mortality Example Dry mouth with Tricyclic Antidepressants Respiratory Depression with Opioids Bleeding with Warfarin Management Reduce Dose or Withhold Drug Consider effects of concomitant therapy Bleeding with Warfarin

14. B izzare (Non-Dose Related) Features Uncommon Not related to the pharmacologic action Unpredictable High mortality Example Immunologic reactions: anaphylaxis to penicillin Idiosyncratic reactions: malignant hyperthermia with general anesthetics Management Withhold and avoid in future Penicillin Allergy

15. C hronic (Dose Related & Time Related) Features Uncommon Related to the cumulative dose Example Hypothalamic-pituitary-adrenal axis suppression by corticosteroids. Osteonecrosis of the jaw with bisphosphonates Management Reduce dose or use an alternate day therapy withdrawal may have to be prolonged Osteonecrosis of Jaw with Bisphosphonates

16. D elayed (Time Related) Features Uncommon Usually dose related Occurs or becomes apparent sometime after use of the drug Example Carcinogenesis Teratogenesis Tardive dyskinesia Leucopenia with lomustine Management Often intractable Tardive dyskinesia

17. E nd of use (Withdrawal) Features Uncommon Occurs soon after withdrawal of the drug Example Withdrawal syndrome with opiates or benzodiazepines (e.g., insomnia, anxiety) Management Reintroduce drug and withdraw slowly Insomnia

18. F ailure (Unexpected Failure of Therapy) Features Common Dose related Often caused by drug interactions Example Inadequate dosage of an oral contraceptive when used with an enzyme inducer. Resistance to antimicrobial agents Management Increase dosage Consider effects of concomitant therapy

19. ADRs…Based on Severity Minor ADRs: No therapy, antidote or prolongation of hospitalization is required. Moderate ADRs: Requires change in drug therapy, specific treatment or prolongs hospital stay by at least 1 day. Severe ADRs: Potentially life threatening, causes permanent damage or requires intensive medical treatment. Lethal ADRs: Directly or indirectly contributes to death of the patient

20. Monitoring ADRs ( Pharmacovigilance ) 1. Detecting adverse drug reaction(ADR ). 2. Documentation of ADR 3. Reporting ADRs to pharmacovigilance centers 4. Causality Assessment (Relationship between the drug and suspected ADRs) Steps Involved:

21. Detection of ADRs Pre- Marketing Studies Post– Marketing Surveillance Spontaneous adverse reaction reporting Epidemiological methods Case Control Studies Cohort Studies

22. During the development of new medicines, their safety is tested in animal models . A great safety risk information such as acute toxicity and organs damage can be generated. If there was no alarming toxicity from animal study, safety tests proceed onto testing in human. Clinical trials are carried out in three different phases prior to submission of a marketing authorization application. At the time of general marketing of a new medicine only the most common (Type A) adverse reactions will be known. Pre- Marketing Studies

23. Passive and Active pharmacovigilance methodologies are used for detection of risk and for the collection of risk information . Powerful and cost effective system for the identification of unknown drug-related risk. Health care practitioner should see it as their duty to report any suspicion of drug causing risk situation in patient under his care . Spontaneous reporting creates signals of previously unknown problems Post- Marketing Studies Spontaneous Adverse Reaction Reporting

24. These methods are used to verify the hypothesis of a causal link between drug exposure and an adverse outcome. Two epidemiological methods most commonly used are: Epidemiological methods Cohort Studies Case Control studies Exposure Outcome Exposed Outcome ? Not Exposed Outcome ? Exposed ? Outcome Exposed ? Control

25. 25 COHORT STUDIES CASE CONTROL STUDIES Patients exposed to a particular drug are followed up actively and systematically and ADR frequencies are compared to an unedxposed control population. Advantage: Reveals unsuspected ADRs Individuals affected by the adverse event being studied are identified. Each case is matched with several disease – free control patients, randomly recruited from the study base. Drug histories of both the groups are traced backwards for the comparison. The suspicion is strengthened if high association is found. Advantage: Can be analysed quickly as number of patients is small.

26. Patient Related Patient’s demographic information. Presenting Complaints Past medication history Drug therapy details including over the counter Current medications Lab data such as haematological , liver and renal function tests. Details of suspected ADR Time of onset and duration of reaction and severity of reaction Details of dose , frequency, and time of administration of drug Duration of treatment and plasma concentration of Drug Data on other risk factors and predisposing factors. Collection of Data For Detection of ADR

27. A- Who can Report? ADR All healthcare professionals (clinicians, dentists, pharmacists, nurses etc) and Non-healthcare professionals including patients can report suspected ADRs. Duly filled suspected ADRs using Yellow Yellow can be send to the hospital based, regional or national PV Monitoring Centre (NPC ). B-Where to Report ? Yellow Form

28. Report serious adverse drug reactions. A reaction is serious when the patient outcome is: Life-threatening Hospitalization (initial or prolonged) Disability (significant, persistent or permanent) Congenital anomaly Required intervention to prevent permanent impairment or damage Report non-serious , known or unknown, frequent or rare ADRs due to Medicines, Vaccines and Herbal products. C-What to report ?

29. Patient initials, Age at onset of reaction, Reaction term(s), Date of onset of reaction, Suspected medication(s) reporter information. D-Mandatory field for suspected ADR reporting form

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31. What happens to the submitted information? ADR reported by HCP, Patient or Others Causality assessment at AMCs Forwaded to NPC through ADR database Data is Analysed & forwarded Global Pharmacovigilance Database (Managed by WHO-UMC) Reports are periodically reviewed by the NPC Information is submitted to the Steering committee of PvPI Suggests required interventions

32. Causality Assessment Causality assessment is the method by which the extent of the relationship between a drug and a suspected reaction is estimated Methods Of Causality Assessment Group-1 Opinion of Experts, Clinical Judgment or Global introspection methods Group-2 Algorithms ( Naranjo’s ) or standardized assessment methods

33. Group-1 Opinion of Experts, Clinical Judgment or Global Introspection methods WHO-UMC causality assesment scale: Causality term Assessment criteria* Certain Event or laboratory test abnormality, with plausible time relationship to drug intake • Cannot be explained by disease or other drugs • Response to withdrawal plausible that is Dechallenge • Event definitive pharmacologically or phenomenologically • Rechallenge satisfactory, if necessary Probable/ Likely Event or laboratory test abnormality, with reasonable time relationship to drug intake • Unlikely to be attributed to disease or other drugs • Response to withdrawal clinically reasonable • Rechallenge not required

34. Causality term Assessment criteria* Possible Event or laboratory test abnormality, with reasonable time relationship to drug intake • Could also be explained by disease or other drugs • Information on drug withdrawal may be lacking or unclear Unlikely Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible) • Disease or other drugs provide plausible explanations Conditional/ Unclassified • Event or laboratory test abnormality • More data for proper assessment needed, or • Additional data under examination Unassessable / Unclassifiable • Report suggesting an adverse reaction • Cannot be judged because information is insufficient or contradictory • Data cannot be supplemented or verified

35. Group-2 Algorithms ( Naranjo’s Algorithms) S.No Questions Yes No Don’t Know 1 Are there previous conclusive reports on this reaction? -1 2 Did the adverse event appear after the suspected drug was given? +2 -1 3 Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given? +1 4 Did the adverse reaction appear when the drug was readministered ? +2 -1 5 Are there alternative causes that could have caused the reaction? -1 2 6 Did the reaction reappear when a placebo was given? -1 +1 7 Was the drug detected in any body fluid in toxic concentrations? +1 8 Was the reaction more severe when the dose was increased, or less severe when the dose was decreased? +1 9 Did the patient have a similar reaction to the same or similar drugs in any previous exposure? +1

36. But Still There Is No Universally Accepted Method For The Causality Assessment Of Adrs Definite ≥ 9 Probable 5-8 Possible 1-4 Unlikely ≤ Scoring