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获取原文件SIGNAL_DETECTION.md
Detailed methodology for pharmacovigilance signal detection, disproportionality analysis, and signal prioritization.
Disproportionality Analysis
Proportional Reporting Ratio (PRR):
PRR = (A/B) / (C/D)
Where:
A = Reports of drug X with event Y
B = Reports of drug X with any event
C = Reports of event Y with any drug (excluding X)
D = Total reports (excluding drug X)
Signal Thresholds:
| Measure | Signal Threshold | Strong Signal |
|---|---|---|
| PRR | >2.0 | >3.0 |
| Chi-squared | >4.0 | >10.0 |
| N (case count) | >=3 | >=10 |
Severity Classification
| Category | Definition | Priority |
|---|---|---|
| Fatal | Death outcome | Highest |
| Life-threatening | Immediate death risk | Very High |
| Hospitalization | Required/prolonged hospitalization | High |
| Disability | Persistent impairment | High |
| Congenital anomaly | Birth defect | High |
| Other serious | Medical intervention required | Medium |
| Non-serious | No serious criteria | Low |
Signal Scoring Formula
Signal Score = PRR x Severity_Weight x log10(Case_Count + 1)
Severity Weights:
- Fatal: 10
- Life-threatening: 8
- Hospitalization: 5
- Disability: 5
- Other serious: 3
- Non-serious: 1
Evidence Grading
| Tier | Symbol | Criteria | Example |
|---|---|---|---|
| T1 | Critical | PRR >10, fatal outcomes, boxed warning | Lactic acidosis |
| T2 | Serious | PRR 3-10, serious outcomes | Hepatotoxicity |
| T3 | Moderate | PRR 2-3, moderate concern | Hypoglycemia |
| T4 | Low | PRR <2, known/expected | GI side effects |
Warning Severity Categories (Label)
| Category | Description |
|---|---|
| Boxed Warning | Most serious, life-threatening |
| Contraindication | Must not use |
| Warning | Significant risk |
| Precaution | Use caution |
PGx Evidence Levels
| Level | Description | Clinical Action |
|---|---|---|
| 1A | CPIC/DPWG guideline, implementable | Follow guideline |
| 1B | CPIC/DPWG guideline, annotation | Consider testing |
| 2A | VIP annotation, moderate evidence | May inform |
| 2B | VIP annotation, weaker evidence | Research |
| 3 | Low-level annotation | Not actionable |
Example: FAERS Signal Interpretation
Strong Signal: Lactic Acidosis
- PRR of 15.2 indicates 15x higher reporting rate than expected
- 89% classified as serious
- 156 fatalities (12.5% case fatality)
- Known class effect of biguanides
- Risk factors: renal impairment, hypoxia, contrast agents
Moderate Signal: Hepatotoxicity
- PRR of 3.1, 234 serious reports, 12 fatal
- Check LFTs if symptoms
Known/Expected: GI Effects
- Diarrhea PRR 2.3, 18% frequency -> Start low, titrate slow
- Nausea PRR 1.8, 12% frequency -> Take with food