MODULE 14: BENEFIT–RISK EVALUATION

Benefit–Risk Evaluation is a continuous, systematic assessment of how the therapeutic benefits of a drug compare against its known and potential risks, using new evidence throughout the product lifecycle.

It ensures that the benefit–risk balance remains favourable for patients.

Key Components of Benefit–Risk Evaluation

1. Case Trends

PV teams monitor:

• Increase in frequency of specific adverse events
• New patterns (e.g., clustering in certain age groups)
• Changes after market expansion
• Trends linked to comorbidities or drug interactions

Why important?
Rising AE trends may signal:

• A new risk
• Worsening of an existing risk
• Need for regulatory action

2. New Safety Findings

From:

• Literature
• ICSRs
• PSUR/PBRER
• Clinical trials
• Epidemiological studies
• Regulatory alerts (FDA/EMA safety communications)

New findings may include:

• New serious adverse reactions
• Increased severity/frequency of known events
• Drug–drug interaction risks
• Off-label risks

3. Efficacy Updates

Benefit side includes:

• New clinical evidence of efficacy
• Real-world performance data
• Subgroup effectiveness (e.g., elderly, children)
• Comparison with competitors or standard therapy

If benefits decrease → risk–benefit may turn unfavourable.

4. Risk Minimization Outcomes

Evaluate how well implemented RMMs are working:

• Are risks decreasing after label updates?
• Are prescribers using the medication safely?
• Are educational materials effective?
• Are high-risk populations avoiding the drug?

Examples of routine RMMs:

• Label updates
• SmPC/PIL warnings
• Boxed warnings

Examples of additional RMMs:

• Controlled access programs
• Prescriber training
• Patient guides

5. Regulatory Decisions

Regulatory bodies continuously assess:

• Whether benefit > risk remains appropriate
• Need for updated warnings
• Need for restriction of indications
• Requirement for post-authorization safety studies (PASS)
• Whether product should remain on the market

Possible decisions:

• Label changes
• RMP updates
• Safety alerts (e.g., DHPC)
• Product recall or suspension

Example (PV Case-Based)

Drug: CardioSafe
Benefit: Reduces stroke risk by 40%
New Finding: 20 new cases of severe liver injury
Trend: Increasing in elderly patients
RMM Outcome: No change despite warnings
Efficacy Update: Benefit remains high but less effective in renal impairment

Benefit–Risk Conclusion:
→ Additional RMMs needed
→ Update labeling to warn elderly
→ Require liver function monitoring