PVC Risk Management & Signal Detection 3 — Questions and Answers
Question 1: In the context of signal detection, what is a 'false positive' signal?
- A confirmed causal drug-event relationship
- A statistical association that does not reflect a true causal relationship (Correct answer)
- A signal detected only in post-marketing data
- An adverse event reported without a suspect drug
Correct answer: A statistical association that does not reflect a true causal relationship
A false positive is a statistical disproportionality that meets detection thresholds but does not represent a real drug-caused effect upon further evaluation.
Question 2: Which of the following best describes the concept of 'Important Potential Risk' in an EU RMP?
- A confirmed adverse reaction listed in the SmPC
- An unconfirmed concern based on preclinical data, mechanism, or class effects that may be causal (Correct answer)
- Any ADR with a reporting rate above 1 per 1,000
- A risk identified only in pediatric populations
Correct answer: An unconfirmed concern based on preclinical data, mechanism, or class effects that may be causal
An Important Potential Risk is a concern for which there is some evidence of association but causality has not been confirmed.
Question 3: The Empirical Bayes Geometric Mean (EBGM) is primarily used in which signal detection system?
- EudraVigilance EVDAS
- FDA FAERS (Multi-item Gamma Poisson Shrinker — MGPS) (Correct answer)
- WHO VigiBase (IC method)
- MHRA Yellow Card system
Correct answer: FDA FAERS (Multi-item Gamma Poisson Shrinker — MGPS)
The FDA uses the Multi-item Gamma Poisson Shrinker (MGPS), which outputs the EBGM as its primary disproportionality statistic in FAERS analyses.
Question 4: Which element of a Risk Management Plan specifically describes what is already known about the drug's safety profile at the time of authorization?
- Pharmacovigilance Plan
- Safety Specification (Correct answer)
- Risk Minimization Plan
- Efficacy Specification
Correct answer: Safety Specification
The Safety Specification summarizes known and potential risks, populations at risk, missing information, and the epidemiology of the condition.
Question 5: A product is withdrawn from the EU market due to an unfavorable benefit-risk balance. Which authority issues the withdrawal decision for centrally authorized products?
- CHMP via the European Commission (Correct answer)
- EMA Pharmacovigilance Risk Assessment Committee (PRAC) alone
- National Competent Authority of the reference member state
- WHO Drug Information Programme
Correct answer: CHMP via the European Commission
For centrally authorized products, the CHMP issues an opinion and the European Commission issues the formal legal decision to suspend or withdraw the marketing authorization.
Question 6: What is the primary purpose of a 'signal triage' step in pharmacovigilance?
- To determine the causality of a confirmed signal
- To prioritize detected signals based on clinical importance and novelty (Correct answer)
- To submit signals to regulatory authorities
- To calculate disproportionality statistics
Correct answer: To prioritize detected signals based on clinical importance and novelty
Signal triage rapidly assesses which detected signals warrant further evaluation, filtering out known reactions and prioritizing those that are new or clinically significant.
Question 7: Under FDA regulations, a REMS with Elements to Assure Safe Use (ETASU) may include all of the following EXCEPT:
- Prescriber certification requirements
- Patient enrollment in a registry
- Mandatory generic substitution prohibition (Correct answer)
- Dispensing only through certified pharmacies
Correct answer: Mandatory generic substitution prohibition
ETASU components focus on safe use conditions (certifications, restricted distribution, monitoring) but do not include prohibitions on generic substitution, which is governed by separate pharmaceutical law.
PVC Risk Management & Signal Detection 3
In the context of signal detection, what is a 'false positive' signal?