Causality assessment scale

Causality assessment of adverse drug reaction

1. Causality Assessment Scale Presenter :- Dr Arun Singh Second Year Resident Doctor Department of Pharmacology SMS Medical College,Jaipur

2. Learning Objectives Introduction Classification of ADR Definition of Causality Assessment Objectives of Causality Assessment Methods Categories of Causality Assessment World Health Organization (WHO)–Uppsala Monitoring Centre (UMC) Some Case Examples Naranjo Scale

3. Introduction The ethymological roots for the word “pharmacovigilance” are : pharmakon (Greek for drug) and vigilare (Latin for a keep watch). World Health Organization (WHO) defined the ADR as “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 physiological function.

4. The main goal of pharmacovigilance is thus to promote the safe and effective use of health products, in particular by providing timely information about the safety of health products to patients, health care professionals, and the public. The ultimate goal of pharmacovigilance is to accurately characterize and optimize the befits/risk ration of a health product throughout its life cycle.

5. Terminology Adverse drug reaction (ADR): It is a non intended reaction to the drug where a positive (direct) causal relationship between the event and the drug is thought, or has been proven, to exist. Adverse event (AE) : Any new clinical experience that occurs after commencing a medicine. By definition, the causal relationship between the AE and the drug is unknown. Causal relationship : It is said to exist when a drug is thought to have caused or contributed to the occurrence of an adverse drug reaction.

6. Classification of Adverse drug reactions Adverse drug reactions are classified into six types (with mnemonics):

7. Definition Causality assessment is the assessment of relationship between a drug treatment and the occurrence of an adverse event. It is basically used for estimate and to investigate that the particular treatment is the cause of an observed and adverse event or not. It is an essential part of ADR report and important task, conducted by National Pharmacovigilance Programme in each country.

8. Objectives of Causality Assessment Provide relationship between the drug and events. Signal detection (“a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously.”) Provide better evaluation of the benefit/harm profiles of drugs. Plays as an essential part of evaluating ADR reports in early warning systems and for regulatory purposes.

9. Methods of Causal Assessment Many researchers developed various methods of causality assessment of ADRs by using different criteria like chronological relationship between the administration of the drug and the occurrence of the ADR, screening for non-drug related causes, confirmation of the reaction by in vivo or in vitro tests, and previous information on similar events attributed to the suspect drug or to its therapeutic class, etc .

10. Three broad categories of various methods of causality assessment:

11. Expert judgment/global introspection Expert judgments are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality.

12. Algorithms

13. Probabilistic methods (Bayesian approaches)

14. WHO causality assessment scale and Naranjo probability scale are the widely used and commonly preferred in most of the practices.

15. World Health Organization (WHO)–Uppsala Monitoring Centre (UMC) causality assessment criteria

16. The WHO–UMC causality assessment method includes the following four criteria : a) Time relationships between the drug use and the adverse event. b) Absence of other competing causes (medications, disease process itself). c) Response to drug withdrawal or dose reduction (dechallenge). d) Response to drug readministration (rechallenge).

17. Causality association 1.Certain 2.Probable 3.Possible 4.Unlikely Certain:-When all four criteria(a,b,c,d) are met. Probable:-When criteria a,b and c are met. Possible:-When only criteria a is met. Unlikely:-When criteria a and b are not met.

18. Besides these four categories, ADR can also be categorized into:- Unclassified/Conditional Unassessable/Unclassifiable Unclassified/Conditional:-Applied when more data is needed and such data is being sought or is already under examination. Unassessable/Unclassifiable:-Finally when the information in a report is incomplete or contradictory and cannot be verified, then it is Unclassifiable.

19. Basic terminologies in WHO-UMC Causality Assessment scale Challenge : Giving of the drug to the patient during the AE or treatment. Dechallenge : Stopping of the drug, usually after an adverse event (AE) or at the end of a planned treatment. Dechallenges may be complete or partial, i.e., the drug is fully stopped or decreased in dose and the AE may fully disappear or only partially decrease. Positive dechallenge: AE disappears after the stopping of the drug. Negative dechallenge: This refers to the AE doesn't disappear after the stopping of the drug.

20. Rechallenge : Restarting of the same drug after having stopped it, usually for an AE. Rechallenges may also be complete or partial. Negative rechallenge : This is the case where the AE does not recur after the drug is restarted. Positive rechallenge AE recurs after restarting the drug. Prechallenge : This is a new term that refers to the use of the same drug at some point in the past.

21. Examples : Certain Dizziness starts 45 minutes later administration of the antihypertensive drug with no concomitant drugs-AE stops on stopping drug (positive dechallenge) & restart when taken again (positive rechallenge). Injection site reaction 30 seconds after a subcutaneous injection. A large tablet gets suck in the pharynx (obstruction) while swallowing it & it has to be removed in the ER.

22. Example: Probably

23. Example: Possibly

24. Example: Unlikely

25. Case Example-1. A female disease, 55 years old with osteoporosis disease. Prescriber give Pamidronate 30 mg on 05/03/2021 Patient report adverse drug reaction like arthrosis, arthritis aggravated on 07/03/2021. Outcome-Not recovered Dechallenge-Negative Q. Assessment related to the drug? Possible

26. Case Example-2. A female disease, 63years old with Paget’s disease(hypercalcemia of malignancy). Prescriber give Pamidronate acid I.V. on 12/03/2021 Other medications-Letrozole, Simvastatin. Patient report adverse drug reaction like synovitis, influenza like symptoms, skeletal pain on 12/03/2021. Dechallenge-Reaction abated Letrozole, Simvastatin Q. Assessment related to the drug? Probable

27. Case Example-3. A male 28 years old health worker, during covid-19 pandemic disease want to done covishield vaccination He goes to vaccination centre to take covishield vaccine at morning on 15/03/2021. After vaccination, he report adverse drug reaction like injection site pain, myalgia and mild fever at night on 15/03/2021. Outcome-recovered(rechallenge) Q. Assessment related to the drug? Certain

28. Naranjo scale Naranjo scale assesses the causality using the traditional categories of definite, probable, possible and doubtful. A ten-elemental questionnaire with yes, no and unknown replies are developed. Based on the replies, the score has been determined into categories. Limitation: The Naranjo Scale does not address the points needed in the assessment of the causality of possible drug interactions.