PVC Signal Detection & Analysis 3 ā Questions and Answers
Question 1: What does the term 'signal of disproportionate reporting' (SDR) specifically mean in pharmacovigilance?
- A drug-event combination reported more frequently than expected based on overall reporting patterns (Correct answer)
- A single serious adverse event report that triggers immediate regulatory action
- A cluster of reports submitted within a 30-day window
- An adverse event that exceeds the population background incidence rate
Correct answer: A drug-event combination reported more frequently than expected based on overall reporting patterns
An SDR indicates that a specific drug-event pair appears in the database at a rate disproportionately higher than what would be expected by chance given the overall reporting distribution.
Question 2: The Proportional Reporting Ratio (PRR) compares the proportion of a specific adverse event for a drug against:
- The proportion of that event for all other drugs in the database (Correct answer)
- The absolute incidence rate of the event in clinical trials
- The number of reports per million prescriptions dispensed
- The WHO-UMC global baseline rate for that event
Correct answer: The proportion of that event for all other drugs in the database
PRR divides the proportion of the event of interest among all reports for the drug by the same proportion across all other drugs in the database.
Question 3: According to the Evans criteria, a PRR-based signal threshold requires all of the following EXCEPT:
- Background incidence rate below 1 per 10,000 patient-years (Correct answer)
- PRR ā„ 2
- Chi-square ā„ 4
- At least 3 case reports
Correct answer: Background incidence rate below 1 per 10,000 patient-years
The Evans criteria specify PRR ā„2, chi-square ā„4, and Nā„3; background incidence rate is not part of the original Evans disproportionality criteria.
Question 4: In Bayesian signal detection using the Multi-item Gamma Poisson Shrinker (MGPS), what does the EB05 value represent?
- The 5th percentile of the posterior distribution of the EBGM, used as a conservative lower bound (Correct answer)
- The expected background count divided by 5
- The 95th percentile confidence interval upper bound
- A threshold above which signals require immediate reporting
Correct answer: The 5th percentile of the posterior distribution of the EBGM, used as a conservative lower bound
EB05 is the lower 5th percentile of the posterior EBGM distribution, meaning a signal must exceed this value (typically >2) to be considered robust.
Question 5: Which of the following best describes a 'qualitative' signal detection method in pharmacovigilance?
- Clinical review of individual case reports by medical experts for biological plausibility (Correct answer)
- Application of the Reporting Odds Ratio formula to spontaneous report databases
- Mining of electronic health records using machine learning algorithms
- Automated calculation of disproportionality statistics on all drug-event pairs
Correct answer: Clinical review of individual case reports by medical experts for biological plausibility
Qualitative signal detection relies on expert clinical judgment to evaluate individual cases for causality, novelty, and biological plausibility rather than statistical thresholds.
Question 6: When stratifying disproportionality analyses by age group, what pharmacovigilance concern is this technique primarily designed to address?
- Confounding by age-related differences in drug use patterns and adverse event susceptibility (Correct answer)
- Regulatory requirements to report pediatric adverse events separately
- Differences in MedDRA coding practices across age-specific clinical settings
- Variation in reporter type (physician vs. consumer) across age cohorts
Correct answer: Confounding by age-related differences in drug use patterns and adverse event susceptibility
Stratification by age controls for confounding because drug exposure patterns and baseline event rates differ substantially by age, which can mask or inflate signals.
Question 7: What is the purpose of the 'triage' step in the signal management process after initial detection?
- Prioritizing signals based on clinical importance, novelty, and public health impact for further evaluation (Correct answer)
- Automatically closing signals that do not meet statistical thresholds
- Submitting all detected signals to health authorities for review
- Archiving signals that have been previously evaluated and closed
Correct answer: Prioritizing signals based on clinical importance, novelty, and public health impact for further evaluation
Triage ranks detected signals so that limited pharmacovigilance resources are directed toward those with the greatest potential safety implications.
PVC Signal Detection & Analysis 3
What does the term 'signal of disproportionate reporting' (SDR) specifically mean in pharmacovigilance?