正文
获取原文件REPORT_TEMPLATES.md
Templates and examples for pharmacovigilance safety report output.
Report File Template
File: [DRUG]_safety_report.md
# Pharmacovigilance Safety Report: [DRUG]
**Generated**: [Date] | **Query**: [Original query] | **Status**: In Progress
---
## Executive Summary
[Researching...]
---
## 1. Drug Identification
### 1.1 Drug Information
[Researching...]
---
## 2. Adverse Event Profile (FAERS)
### 2.1 Top Adverse Events
[Researching...]
### 2.2 Serious Adverse Events
[Researching...]
### 2.3 Signal Analysis
[Researching...]
---
## 3. FDA Label Safety Information
### 3.1 Boxed Warnings
[Researching...]
### 3.2 Contraindications
[Researching...]
### 3.3 Warnings and Precautions
[Researching...]
---
## 4. Pharmacogenomic Risk Factors
### 4.1 Actionable Variants
[Researching...]
### 4.2 Testing Recommendations
[Researching...]
---
## 5. Clinical Trial Safety
### 5.1 Trial Summary
[Researching...]
### 5.2 Adverse Events in Trials
[Researching...]
---
## 6. Prioritized Safety Signals
### 6.1 Critical Signals
[Researching...]
### 6.2 Moderate Signals
[Researching...]
---
## 7. Risk-Benefit Assessment
[Researching...]
---
## 8. Clinical Recommendations
### 8.1 Monitoring Recommendations
[Researching...]
### 8.2 Patient Counseling Points
[Researching...]
### 8.3 Contraindication Checklist
[Researching...]
---
## 9. Data Gaps & Limitations
[Researching...]
---
## 10. Data Sources
[Will be populated as research progresses...]
Citation Format
Every safety signal MUST include source:
### Signal: Hepatotoxicity
- **PRR**: 3.2 (95% CI: 2.8-3.7)
- **Cases**: 1,247 reports
- **Serious**: 892 (71.5%)
- **Fatal**: 23
*Source: FAERS via `FAERS_count_reactions_by_drug_event` (Q1 2020 - Q4 2025)*
Phase Output Examples
Drug Identification Output
## 1. Drug Identification
| Property | Value |
|----------|-------|
| **Generic Name** | Metformin |
| **Brand Names** | Glucophage, Fortamet, Glumetza |
| **Drug Class** | Biguanide antidiabetic |
| **ChEMBL ID** | CHEMBL1431 |
| **Mechanism** | AMPK activator, hepatic gluconeogenesis inhibitor |
| **First Approved** | 1994 (US) |
*Source: DailyMed via `DailyMed_search_spls`, ChEMBL*
FAERS Output
## 2. Adverse Event Profile (FAERS)
**Data Period**: Q1 2020 - Q4 2025
**Total Reports for Drug**: 45,234
### Top Adverse Events by Frequency
| Rank | Adverse Event | Reports | PRR | 95% CI | Serious (%) | Fatal |
|------|---------------|---------|-----|--------|-------------|-------|
| 1 | Diarrhea | 8,234 | 2.3 | 2.1-2.5 | 12% | 3 |
| 2 | Nausea | 6,892 | 1.8 | 1.6-2.0 | 8% | 0 |
| 3 | Lactic acidosis | 1,247 | 15.2 | 12.8-17.9 | 89% | 156 |
### Serious Adverse Events Only
| Adverse Event | Serious Reports | Fatal | PRR | Signal |
|---------------|-----------------|-------|-----|--------|
| Lactic acidosis | 1,110 | 156 | 15.2 | **STRONG** |
| Acute kidney injury | 678 | 34 | 4.2 | Moderate |
*Source: FAERS via `FAERS_count_reactions_by_drug_event`*
Label Warnings Output
## 3. FDA Label Safety Information
### 3.1 Boxed Warning
**LACTIC ACIDOSIS**
> Metformin can cause lactic acidosis, a rare but serious complication.
> Risk increases with renal impairment, sepsis, dehydration, excessive
> alcohol intake, hepatic impairment, and acute heart failure.
> **Contraindicated in patients with eGFR <30 mL/min/1.73m2**
### 3.2 Contraindications
| Contraindication | Rationale |
|------------------|-----------|
| eGFR <30 mL/min/1.73m2 | Lactic acidosis risk |
| Acute/chronic metabolic acidosis | May worsen acidosis |
| Hypersensitivity to metformin | Allergic reaction |
### 3.3 Warnings and Precautions
| Warning | Clinical Action |
|---------|-----------------|
| Vitamin B12 deficiency | Monitor B12 levels annually |
| Hypoglycemia with insulin | Reduce insulin dose |
| Radiologic contrast | Hold 48h around procedure |
*Source: DailyMed via `DailyMed_search_spls`*
Pharmacogenomics Output
## 4. Pharmacogenomic Risk Factors
### Clinically Actionable Variants
| Gene | Variant | Phenotype | Recommendation | Level |
|------|---------|-----------|----------------|-------|
| SLC22A1 | rs628031 | Reduced OCT1 | Reduced metformin response | 2A |
| SLC22A1 | rs36056065 | Loss of function | Consider alternative | 2A |
**No CPIC/DPWG guidelines currently exist for metformin**
*Source: PharmGKB via `PharmGKB_search_drugs`*
Clinical Trial Safety Output
## 5. Clinical Trial Safety Data
### Phase 3 Trial Summary
| Trial | N | Duration | Serious AEs (Drug) | Serious AEs (Placebo) | Deaths |
|-------|---|----------|-------------------|----------------------|--------|
| UKPDS | 1,704 | 10 yr | 12.3% | 14.1% | 8.2% vs 9.1% |
### Common Adverse Events in Trials
| Adverse Event | Drug (%) | Placebo (%) | Difference |
|---------------|----------|-------------|------------|
| Diarrhea | 53% | 12% | +41% |
| Nausea | 26% | 8% | +18% |
*Source: ClinicalTrials.gov via `search_clinical_trials`*
Prioritized Signals Output
## 6. Prioritized Safety Signals
### Critical Signals (Immediate Attention)
| Signal | PRR | Fatal | Score | Action |
|--------|-----|-------|-------|--------|
| Lactic acidosis | 15.2 | 156 | 482 | Boxed warning exists |
### Moderate Signals (Monitor)
| Signal | PRR | Serious | Score | Action |
|--------|-----|---------|-------|--------|
| Hepatotoxicity | 3.1 | 234 | 52 | Check LFTs if symptoms |
### Known/Expected (Manage Clinically)
| Signal | PRR | Frequency | Management |
|--------|-----|-----------|------------|
| Diarrhea | 2.3 | 18% | Start low, titrate slow |
Pathway & Mechanism Output
## 5.5 Pathway & Mechanism Context
### Drug Metabolism Pathways (KEGG)
| Pathway | Relevance | Safety Implication |
|---------|-----------|-------------------|
| Drug metabolism - cytochrome P450 | Primary metabolism | CYP2C9 interactions |
| Gluconeogenesis inhibition | MOA | Lactic acidosis mechanism |
### Mechanistic Basis for Key AEs
| Adverse Event | Pathway Mechanism |
|---------------|-------------------|
| Lactic acidosis | Mitochondrial complex I inhibition |
| GI intolerance | Serotonin release in gut |
| B12 deficiency | Intrinsic factor interference |
*Source: KEGG, Reactome*
Literature Evidence Output
## 5.6 Literature Evidence
### Key Safety Studies
| PMID | Title | Year | Citations | Finding |
|------|-------|------|-----------|---------|
| 29234567 | Metformin and lactic acidosis: meta-analysis | 2020 | 245 | Risk 4.3/100,000 |
### Recent Preprints (Not Peer-Reviewed)
| Source | Title | Posted | Relevance |
|--------|-------|--------|-----------|
| MedRxiv | Novel metformin safety signal in elderly | 2024-01 | Age-related risk |
**Note**: Preprints have NOT undergone peer review.
*Source: PubMed, BioRxiv, MedRxiv, OpenAlex*
Completeness Checklist
Phase 1: Drug Identification
- Generic name resolved
- Brand names listed
- Drug class identified
- ChEMBL/DrugBank ID obtained
- Mechanism of action stated
Phase 2: FAERS Analysis
- >=20 adverse events queried
- PRR calculated for top events
- Serious/fatal counts included
- Signal thresholds applied
- Time period stated
Phase 3: Label Warnings
- Boxed warnings extracted (or "None")
- Contraindications listed
- Key warnings summarized
- Drug interactions noted
Phase 4: Pharmacogenomics
- PharmGKB queried
- Actionable variants listed (or "None")
- Evidence levels provided
- Testing recommendations stated
Phase 5: Clinical Trials
- Phase 3/4 trials searched
- Serious AE rates compared
- Discontinuation rates noted
Phase 6: Signal Prioritization
- Signals ranked by score
- Critical signals flagged
- Actions recommended
Phase 7-8: Synthesis
- Risk-benefit assessment provided
- Monitoring recommendations listed
- Patient counseling points included
Data File Outputs
In addition to the report, generate:
[DRUG]_adverse_events.csv- Ranked AEs with counts/signals[DRUG]_pharmacogenomics.csv- PGx variants and recommendations