Causality assessment of adverse drug reactions (ADR) is the process of determining the likelihood or probability that a drug is responsible for causing an observed adverse event. It involves evaluating the relationship between the drug exposure and the occurrence of the adverse event based on available evidence, such as clinical data, patient characteristics, temporal association, and alternative explanations. Causality assessment is an essential component of pharmacovigilance and drug safety monitoring. Here are some commonly used methods and scales for causality assessment: Naranjo Algorithm: The Naranjo algorithm is a widely used causality assessment tool. It assigns a numerical score based on specific questions related to the temporal relationship, alternative causes, dechallenge/rechallenge, and previous knowledge of the drug-event association. The total score classifies the causality as definite, probable, possible, or doubtful. World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Scale: The WHO-UMC scale is a standardized method for assessing causality in ADRs. It consists of a set of criteria that consider factors such as the time to onset of the event, the response to dechallenge/rechallenge, alternative causes, and the presence of supporting information. Causality is categorized as certain, probable/likely, possible, unlikely, or unclassified. Bradford Hill Criteria: The Bradford Hill criteria are a set of nine factors used to assess causality in various fields, including pharmacovigilance. These criteria include strength of association, consistency, specificity, temporality, biological plausibility, coherence, experimental evidence, analogy, and dose-response relationship. These factors are considered collectively to determine the likelihood of a causal relationship. CIOMS (Council for International Organizations of Medical Sciences) Scale: The CIOMS scale provides a structured approach to assessing causality by considering factors such as the temporal relationship, the presence of alternative causes, drug dechallenge/rechallenge, and the consistency of the event with the drug's known pharmacology.

1. Welcome
Causality Assessment of Adverse Drug Reaction
Ashwini Tamkhane
Bachelor of Pharmacy
CSRPL_INT_ONL_WKD_161/0922
11/8/2022
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2. Index
• Introduction
• Objectives
• Methods of causality assessment
1. Expert Judgment/ Global Introspection
2. Algorithm’s
3. Probabilistic Method
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3. Introduction
• Causality assessment is the assessment of the relationship between a drug
treatment and the occurrence of an adverse event.
• It is also used to evaluate and to check that the particular treatment is the
cause of adverse event or not.
• It is an essential part of Adverse Drug Reaction(ADR) report and import
task, conducted by National Pharmacovigilance Program in each country.
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4. Objectives
❖Provide Relationship between drug and events.
❖Signal detection- A possible causal relationship between adverse event and a drug, the
relationship being unknown or incompletely documented previously.
❖Provide better evaluation of the benefits/risks profiles of drug.
❖Plays as an essential part of evaluating ADR reports in early warning system and for regulatory
purposes.
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5. Methods
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CAUSALITY
ASSESSMENT
Expert Judgment/
Global Introspection
Probabilistic Method
Algorithms
Causality Assessment of
Vaccines Related
Adverse Event

6. 1] Expert Judgment/ Global Introspection
⮚ It is a process in which an expert expresses judgments about considering all
available data relevant to suspected ADR
⮚Assessment of ADR is either done by single expert evaluator or by a group of
expert evaluators.
⮚As evaluation and assessment of ADR by these expert is purely bases on their
respective knowledge and experience about the subject of interest.
⮚Two methods based on expert opinion or global introspection
A) Swedish Method by Wilhom et al.
B) World Health Organization(WHO)-Uppasala Monitoring
Centre(UMC) causality assessment criteria.
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7. (B) World Health Organization(WHO)-Uppsala Monitoring
Centre (UMC) causality assessment criteria.
⮚Widely and globally accepted method .
⮚WHO-UMC system provides practical tool for assessment of case report for
International drug monitoring.
⮚System is used to detect unknown and unexpected adverse drug reaction.
⮚Assessment is bases on following four criteria
a) Time relationship between the drug use and the adverse event
b) Absence of other competing causes( medication, disease process itself)
c) Response to drug withdrawal or dose reduction (de-challenge)
d) Response to drug re-administration (re-challenge)
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8. ⮚The level of causal association is grouped into four categories which are
based on a number of the above criteria being met.
1) Certain
2) Probable
3) Possible
4) Unlikely
Beside these four categories ADR can also be categorized into
1) Unclassified/Conditional- Applied when more data is needed and such data
is being sought or is already under examination
2) Unassessable/Unclassifiable- Finally when the information in a report is
incomplete or contradictory and cannot be verified, then it is Unclassifiable
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9. Categories of Causality using WHO Causality
Assessment Criteria
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Very likely
Probable
Possible
Unlikely
Unrelated
Unclassifiable
Vaccine reaction
Injection Reaction
Programmatic Error
Coincidental Events
Insufficient Evidence to Classify

10. 2) ALGORITHMS
⮚It consists of a problem-specific flowchart with step-by-step instruction on
how to arrive at an answer.
⮚Actually, its form contain some questionnaire, whose answers provide the
causality of particular ADR
⮚It gives structured and standardize methods of assessment in a systetmatic
approach
⮚Assessment of ADRs based on parameters such as
Time to onset of the ADR or temporal sequence.
Previous drug/adverse reaction history.
Dechallenge and Rechallenge
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11. 3) Problastic
⮚ Causality assessment based on study of prior probability
and posterior probability.
⮚ The prior probability is calculated from epidemiological
information.
⮚ The posterior probability combines this epidiological
background information with the evidence in the individual
case.
⮚ This methods allows the simultaneous assessment of
multiple causes.
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12. 4) Causality Assessment of Vaccine related Adverse Events
⮚ Vaccines are administered on large scale to help healthy individual, children, infants and
neonates.
⮚ So vaccines must with high degree of safety
⮚ Method developed by the Advisory Committee on Causality Assessment(ACCA) in Canada.
⮚ACCA is composed of specialist in pediatrics, epidemiology, infectious disease, immunology,
neurology, pathology, adverse event surveillance and microbiology.
⮚They review individual cases in a systematic stepwise manner to categorize them on a
specially designed causality assessment form.
⮚This causality assessment form consist of seven section.
Section one Section two Section three
Section Four Section five Section six
Section seven.
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13. ▪ Section one- It is relates to the reason for reporting and whether the committee agreed
with both the diagnosis that was made and the statement of severity
▪ Section Two- section two takes the evaluators through several important factors like
frequency of occurrence of adverse events, similar events known to occur with other disease
,vaccine-event interval compatible with event, similar symptoms in past, concomitant drug
of other conditions for assessment of causality.
▪ Section Three- section three relates to causality assessment by using WHO-UMC criteria.
▪ Section Four- It permits brief summary of case with important element and discussion
which contributed to the final assessment of causality.
▪ Section Five- it permits recommendation for improving immunization or case procedures to
be written.
▪ Section six- considers whether the case could be useful for educational purpose.
▪ Section seven- considers whether the case could be useful for publication.
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14. Thank You!
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