tooluniverse-pharmacovigilance

Pharmacovigilance Safety Analyzer Systematic drug safety analysis using FAERS adverse event data, FDA labeling, PharmGKB pharmacogenomics, and clinical trial safety signals. KEY PRINCIPLES : Report-first approach - Create report file FIRST, update progressively Signal quantification - Use disproportionality measures (PRR, ROR) Severity stratification - Prioritize serious/fatal events Multi-source triangulation - FAERS, labels, trials, literature Pharmacogenomic context - Include genetic risk factors Actionable output - Risk-benefit summary with recommendations English-first queries - Always use English drug names in tool calls 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]" Critical Workflow Requirements Report-First Approach (MANDATORY) Create [DRUG]_safety_report.md FIRST with all section headers and [Researching...] placeholders Progressively update as data is gathered 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. 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 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 Phase 1: Drug Disambiguation Search DailyMed via DailyMed_search_spls(drug_name=...) for NDC, SPL setid, generic name Search ChEMBL via ChEMBL_search_drugs(query=...) for molecule ID, max phase Document: generic name, brand names, drug class, mechanism, approval date Phase 2: Adverse Event Profiling (FAERS) Query FAERS_count_reactions_by_drug_event(drug_name=..., limit=50) for top events For each event, get detailed breakdown (serious, fatal, hospitalization counts) Calculate PRR: (A/B) / (C/D) where A=drug+event, B=drug+any, C=event+any_other, D=total_other 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 Get label via DailyMed_get_spl_by_set_id(setid=...) Extract: boxed warnings, contraindications, warnings/precautions, drug interactions Categorize severity: Boxed Warning > Contraindication > Warning > Precaution Phase 4: Pharmacogenomic Risk Search PharmGKB_search_drug(query=...) for clinical annotations Document actionable variants with evidence levels (1A/1B/2A/2B/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 Search search_clinical_trials(intervention=..., phase="Phase 3", status="Completed") Extract serious AE rates, discontinuation rates, deaths Compare drug vs placebo rates Phase 5.5: Pathway & Mechanism Context Query KEGG for drug metabolism pathways Analyze target pathways for mechanistic basis of AEs Document pathway-AE relationships Phase 5.6: Literature Intelligence PubMed: PubMed_search_articles(query='"[drug]" AND (safety OR adverse OR toxicity)') BioRxiv/MedRxiv: Search for recent preprints (flag as not peer-reviewed) 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 Output Report Save as [DRUG]_safety_report.md . See REPORT_TEMPLATES.md for the full report structure and example outputs. 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 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 Completeness Checklist See CHECKLIST.md for the full phase-by-phase verification checklist. 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