PVC Risk Management & Signal Detection 2 — Questions and Answers
Question 1: Which regulatory framework requires a Risk Management Plan (RMP) to be submitted alongside a Marketing Authorization Application in the EU?
- ICH E2E guideline
- EU GVP Module V (Correct answer)
- FDA REMS guidance
- ICH Q10
Correct answer: EU GVP Module V
EU GVP Module V governs Risk Management Systems and mandates an RMP for new MAAs in the European Union.
Question 2: What is the minimum disproportionality threshold commonly used with the Reporting Odds Ratio (ROR) to flag a potential signal?
- ROR > 1.0 with 95% CI lower bound > 1 (Correct answer)
- ROR > 2.0 with any CI
- ROR > 1.5 with p < 0.05
- ROR > 3.0 regardless of CI
Correct answer: ROR > 1.0 with 95% CI lower bound > 1
A signal is typically flagged when the ROR exceeds 1.0 and the lower bound of the 95% confidence interval is also above 1.
Question 3: In signal management, what does the term 'signal validation' refer to?
- Confirming the signal in a clinical trial
- Assessing whether data support a causal association beyond background noise (Correct answer)
- Publishing the signal in a peer-reviewed journal
- Notifying regulators of the new safety finding
Correct answer: Assessing whether data support a causal association beyond background noise
Signal validation evaluates whether the available data provide sufficient evidence that the detected association is more than a statistical artifact.
Question 4: A Risk Minimization Measure (RMM) that restricts prescribing to certified specialists is classified as:
- Routine RMM
- Additional RMM — educational
- Additional RMM — restricted access (Correct answer)
- Pharmacovigilance-only measure
Correct answer: Additional RMM — restricted access
Restricted access programs, such as prescriber certification requirements, are categorized as additional RMMs that control who can prescribe or dispense a medicine.
Question 5: Which metric does the Proportional Reporting Ratio (PRR) compare?
- Incidence in exposed vs. unexposed populations
- Proportion of reports for a drug-event pair vs. all reports for that event across all drugs (Correct answer)
- Number of serious vs. non-serious AEs for one product
- Expected vs. observed event rates in clinical trials
Correct answer: Proportion of reports for a drug-event pair vs. all reports for that event across all drugs
The PRR compares the proportion of reports for a specific drug-event combination to the proportion of the same event reported for all other drugs in the database.
Question 6: According to ICH E2E, which document provides the scientific rationale for proposed pharmacovigilance activities and risk minimization?
- Periodic Safety Update Report (PSUR)
- Pharmacovigilance System Master File (PSMF)
- Risk Management Plan (RMP) (Correct answer)
- Development Safety Update Report (DSUR)
Correct answer: Risk Management Plan (RMP)
ICH E2E describes the Risk Management Plan as the document that outlines the safety specification, pharmacovigilance plan, and risk minimization strategy.
Question 7: A MAH conducts a Targeted Follow-up questionnaire for a specific adverse event. This is an example of:
- Routine pharmacovigilance
- Additional pharmacovigilance activity (Correct answer)
- Risk minimization measure
- Signal prioritization
Correct answer: Additional pharmacovigilance activity
Targeted follow-up questionnaires are additional pharmacovigilance activities used to collect more detailed information on specific safety concerns.
PVC Risk Management & Signal Detection 2
Which regulatory framework requires a Risk Management Plan (RMP) to be submitted alongside a Marketing Authorization Application in the EU?