Lesson 8 & 9- Causality Assessment

Question 1

What is causality assessment? What is causality assessment?

Answer 1

A method to determine the extent of the relationship between a drug and a suspected adverse reaction.

Question 2

Define ADR (Adverse Drug Reaction).

Answer 2

An unintended, harmful effect attributable to a drug at normal doses.

Question 3

Define AE (Adverse Event).

Answer 3

An undesirable occurrence during drug treatment, not necessarily causally linked to the drug.

Question 4

List the basic criteria for causality assessment.

Answer 4

1. Temporal relationship.
2. Dechallenge (improvement after stopping the drug).
3. Rechallenge (recurrence upon re-exposure).
4. Biological plausibility.
5. Exclusion of other causes (diseases, drugs).

Question 5

What is temporal relationship?

Answer 5

The event occurs within a plausible timeframe after drug administration.

Question 6

What is dechallenge?

Answer 6

Recurrence of the adverse event after restarting the drug.

Question 7

What is rechallenge?

Answer 7

Recurrence of the adverse event after restarting the drug.

Question 8

What defines a “Certain” causality per WHO-UMC?

Answer 8

• Clear causal evidence.
• Positive dechallenge and rechallenge.
• Other causes ruled out.

Question 9

What defines “Probable” causality per WHO-UMC?

Answer 9

• Likely causal relationship.
• Positive dechallenge.
• Other causes unlikely.

Question 10

What defines “Possible” causality per WHO-UMC?

Answer 10

• Temporal relationship exists.
• Other causes may contribute.
• Insufficient evidence for higher causality.

Question 11

What defines “Unlikely” causality per WHO-UMC?

Answer 11

• Little evidence of causality.
• Alternative explanation exists.

Question 12

What Naranjo score indicates a “Definite” ADR?

Answer 12

≥9.

Question 13

What Naranjo score indicates a “Probable” ADR?

Answer 13

5–8.

Question 14

What Naranjo score indicates a “Possible” ADR?

Answer 14

1–4.

Question 15

Which Naranjo question assesses rechallenge?

Answer 15

“Did the adverse event reappear when the drug was readministered?”

Question 16

How is biological plausibility addressed in the Naranjo scale?

Answer 16

Alternative causes?
Previous conclusive reports?

Question 17

A patient develops dizziness 45 minutes after taking an antihypertensive. Symptoms resolve on stopping the drug and recur on rechallenge. What is the causality?

Answer 17

Certain (WHO-UMC).

Question 18

A patient develops synovitis after IV pamidronate. Symptoms resolve on stopping the drug. Other medications include letrozole. What is the causality?

Answer 18

Possible (concomitant drugs may contribute).

Question 19

A patient’s arthritis worsens after pamidronate. No improvement on dechallenge. What is the causality?

Answer 19

Unlikely (negative dechallenge).

Question 20

List challenges in causality assessment.

Answer 20

• Polypharmacy.
• Underlying diseases mimicking ADRs.
• Incomplete information.
• Variability in clinical responses.

Question 21

How does WHO-UMC differ from Naranjo?

Answer 21

• WHO-UMC: Qualitative, uses categories (Certain/Probable/Possible).
• Naranjo: Quantitative, uses a scoring system (0–13).

Question 22

What is global introspection?

Answer 22

Expert judgment-based causality assessment (subjective).

Question 23

What is the maximum possible score on the Naranjo scale?

Answer 23

13 (though scores ≥9 indicate “Definite” ADR).

Question 24

How is Question 5 in the Naranjo scale scored?

Answer 24

• Yes (alternative causes exist): -1
• No (no alternative causes): +2

Question 25

When is a case labeled **"Unclassifiable"** per WHO-UMC?

Answer 25

When insufficient information (e.g., missing dechallenge data, unclear timeline) prevents a causality judgment.

Question 26

What is a limitation of **probabilistic methods** (e.g., Bayesian analysis) in causality assessment?

Answer 26

Requires extensive data and specialized skills, making it impractical for routine use.

Question 27

Why was the **aggravated arthritis case** (negative dechallenge) deemed **"Unlikely"**?

Answer 27

No improvement after stopping the drug (negative dechallenge) and alternative explanations (e.g., disease progression).