tooluniverse-pharmacovigilance

name	tooluniverse-pharmacovigilance
description	Analyze drug safety signals from FDA adverse event reports, label warnings, and pharmacogenomic data. Calculates disproportionality measures (PRR, ROR), identifies serious adverse events, assesses pharmacogenomic risk variants. Use when asked about drug safety, adverse events, post-market surveillance, or risk-benefit assessment.

Pharmacovigilance Safety Analyzer

Systematic drug safety analysis using FAERS adverse event data, FDA labeling, PharmGKB pharmacogenomics, and clinical trial safety signals.

KEY PRINCIPLES:

1. Report-first approach - Create report file FIRST, update progressively
2. Signal quantification - Use disproportionality measures (PRR, ROR)
3. Severity stratification - Prioritize serious/fatal events
4. Multi-source triangulation - FAERS, labels, trials, literature
5. Pharmacogenomic context - Include genetic risk factors
6. Actionable output - Risk-benefit summary with recommendations
7. English-first queries - Always use English drug names in tool calls

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When to Use

Apply when user asks:

• "What are the safety concerns for [drug]?"
• "What adverse events are associated with [drug]?"
• "Is [drug] safe? What are the risks?"
• "Compare safety profiles of [drug A] vs [drug B]"
• "Pharmacovigilance analysis for [drug]"

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Critical Workflow Requirements

Report-First Approach (MANDATORY)

1. Create [DRUG]_safety_report.md FIRST with all section headers and [Researching...] placeholders
2. Progressively update as data is gathered
3. Output separate data files: [DRUG]_adverse_events.csv and [DRUG]_pharmacogenomics.csv

Citation Requirements (MANDATORY)

Every safety signal MUST include source tool, data period, PRR, case counts, and serious/fatal breakdown.

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Tool Parameter Reference (CRITICAL)

Tool	WRONG Parameter	CORRECT Parameter
FAERS_count_reactions_by_drug_event	drug	drug_name
DailyMed_search_spls	name	drug_name
PharmGKB_search_drug	drug	query
OpenFDA_get_drug_events	drug_name	search

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Workflow Overview

Phase 1: Drug Disambiguation
  -> Resolve drug name, get identifiers (ChEMBL, DrugBank)

Phase 2: Adverse Event Profiling (FAERS)
  -> Query FAERS, calculate PRR, stratify by seriousness

Phase 3: Label Warning Extraction
  -> DailyMed boxed warnings, contraindications, precautions

Phase 4: Pharmacogenomic Risk
  -> PharmGKB clinical annotations, high-risk genotypes

Phase 5: Clinical Trial Safety
  -> ClinicalTrials.gov Phase 3/4 safety data

Phase 5.5: Pathway & Mechanism Context
  -> KEGG drug metabolism, target pathway analysis

Phase 5.6: Literature Intelligence
  -> PubMed, BioRxiv/MedRxiv, OpenAlex citation analysis

Phase 6: Signal Prioritization
  -> Rank by PRR x severity x frequency

Phase 7: Report Synthesis

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Phase 1: Drug Disambiguation

1. Search DailyMed via DailyMed_search_spls(drug_name=...) for NDC, SPL setid, generic name
2. Search ChEMBL via ChEMBL_search_drugs(query=...) for molecule ID, max phase
3. Document: generic name, brand names, drug class, mechanism, approval date

Phase 2: Adverse Event Profiling (FAERS)

1. Query FAERS_count_reactions_by_drug_event(drug_name=..., limit=50) for top events
2. For each event, get detailed breakdown (serious, fatal, hospitalization counts)
3. Calculate PRR: (A/B) / (C/D) where A=drug+event, B=drug+any, C=event+any_other, D=total_other
4. Apply signal thresholds: PRR > 2.0 (signal), > 3.0 (strong signal), case count >= 3

Severity classification:

• Fatal (highest priority), Life-threatening, Hospitalization, Disability, Other serious, Non-serious

See SIGNAL_DETECTION.md for detailed disproportionality formulas and example output tables.

Phase 3: Label Warning Extraction

1. Get label via DailyMed_get_spl_by_set_id(setid=...)
2. Extract: boxed warnings, contraindications, warnings/precautions, drug interactions
3. Categorize severity: Boxed Warning > Contraindication > Warning > Precaution

Phase 4: Pharmacogenomic Risk

1. Search PharmGKB_search_drug(query=...) for clinical annotations
2. Document actionable variants with evidence levels (1A/1B/2A/2B/3)
3. Note CPIC/DPWG guideline status

PGx Evidence Levels:

Level	Description	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

Phase 5: Clinical Trial Safety

1. Search search_clinical_trials(intervention=..., phase="Phase 3", status="Completed")
2. Extract serious AE rates, discontinuation rates, deaths
3. Compare drug vs placebo rates

Phase 5.5: Pathway & Mechanism Context

1. Query KEGG for drug metabolism pathways
2. Analyze target pathways for mechanistic basis of AEs
3. Document pathway-AE relationships

Phase 5.6: Literature Intelligence

1. PubMed: PubMed_search_articles(query='"[drug]" AND (safety OR adverse OR toxicity)')
2. BioRxiv/MedRxiv: Search for recent preprints (flag as not peer-reviewed)
3. OpenAlex: Citation analysis for key safety papers

Phase 6: Signal Prioritization

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

Categorize signals:

• Critical (immediate attention): High PRR + fatal outcomes
• Moderate (monitor): Moderate PRR + serious outcomes
• Known/Expected (manage clinically): Low PRR, in label

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Output Report

Save as [DRUG]_safety_report.md. See REPORT_TEMPLATES.md for the full report structure and example outputs.

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Evidence Grading

Tier	Criteria	Example
T1	PRR >10, fatal outcomes, boxed warning	Lactic acidosis
T2	PRR 3-10, serious outcomes	Hepatotoxicity
T3	PRR 2-3, moderate concern	Hypoglycemia
T4	PRR <2, known/expected	GI side effects

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Fallback Chains

Primary Tool	Fallback 1	Fallback 2
FAERS_count_reactions_by_drug_event	OpenFDA_get_drug_events	Literature search
DailyMed_get_spl_by_set_id	FDA_drug_label_search	DailyMed website
PharmGKB_search_drug	CPIC_get_guidelines	Literature search
search_clinical_trials	ClinicalTrials.gov API	PubMed for trial results

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Completeness Checklist

See CHECKLIST.md for the full phase-by-phase verification checklist.

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References

• FAERS: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers
• DailyMed: https://dailymed.nlm.nih.gov
• PharmGKB: https://www.pharmgkb.org
• ClinicalTrials.gov: https://clinicaltrials.gov
• OpenFDA: https://open.fda.gov
• KEGG Drug: https://www.genome.jp/kegg/drug
• Tool documentation: TOOLS_REFERENCE.md