tooluniverse-adverse-event-detection

安装量: 113
排名: #7548

安装

npx skills add https://github.com/mims-harvard/tooluniverse --skill tooluniverse-adverse-event-detection
Adverse Drug Event Signal Detection & Analysis
Automated pipeline for detecting, quantifying, and contextualizing adverse drug event signals using FAERS disproportionality analysis, FDA label mining, mechanism-based prediction, and literature evidence. Produces a quantitative Safety Signal Score (0-100) for regulatory and clinical decision-making.
KEY PRINCIPLES
:
Signal quantification first
- Every adverse event must have PRR/ROR/IC with confidence intervals
Serious events priority
- Deaths, hospitalizations, life-threatening events always analyzed first
Multi-source triangulation
- FAERS + FDA labels + OpenTargets + DrugBank + literature
Context-aware assessment
- Distinguish drug-specific vs class-wide vs confounding signals
Report-first approach
- Create report file FIRST, update progressively
Evidence grading mandatory
- T1 (regulatory/boxed warning) through T4 (computational)
English-first queries
- Always use English drug names in tool calls, respond in user's language
Reference files
(in this directory):
PHASE_DETAILS.md
- Detailed tool calls, code examples, and output templates per phase
REPORT_TEMPLATE.md
- Full report template and completeness checklist
TOOL_REFERENCE.md
- Tool parameter reference and fallback chains
QUICK_START.md
- Quick examples and common drug names
When to Use
Apply when user asks:
"What are the safety signals for [drug]?"
"Detect adverse events for [drug]"
"Is [drug] associated with [adverse event]?"
"What are the FAERS signals for [drug]?"
"Compare safety of [drug A] vs [drug B] for [adverse event]"
"What are the serious adverse events for [drug]?"
"Are there emerging safety signals for [drug]?"
"Post-market surveillance report for [drug]"
"Pharmacovigilance signal detection for [drug]"
Differentiation from tooluniverse-pharmacovigilance
This skill focuses specifically on
signal detection and quantification
using disproportionality analysis (PRR, ROR, IC) with statistical rigor, produces a quantitative
Safety Signal Score (0-100)
, and performs
comparative safety analysis
across drug classes.
Workflow Overview
Phase 0: Input Parsing & Drug Disambiguation
Parse drug name, resolve to ChEMBL ID, DrugBank ID
Identify drug class, mechanism, and approved indications
|
Phase 1: FAERS Adverse Event Profiling
Top adverse events by frequency
Seriousness and outcome distributions
Demographics (age, sex, country)
|
Phase 2: Disproportionality Analysis (Signal Detection)
Calculate PRR, ROR, IC with 95% CI for each AE
Apply signal detection criteria
Classify signal strength (Strong/Moderate/Weak/None)
|
Phase 3: FDA Label Safety Information
Boxed warnings, contraindications
Warnings and precautions, adverse reactions
Drug interactions, special populations
|
Phase 4: Mechanism-Based Adverse Event Context
Target-based AE prediction (OpenTargets safety)
Off-target effects, ADMET predictions
Drug class effects comparison
|
Phase 5: Comparative Safety Analysis
Compare to drugs in same class
Identify unique vs class-wide signals
Head-to-head disproportionality comparison
|
Phase 6: Drug-Drug Interactions & Risk Factors
Known DDIs causing AEs
Pharmacogenomic risk factors (PharmGKB)
FDA PGx biomarkers
|
Phase 7: Literature Evidence
PubMed safety studies, case reports
OpenAlex citation analysis
Preprint emerging signals (EuropePMC)
|
Phase 8: Risk Assessment & Safety Signal Score
Calculate Safety Signal Score (0-100)
Evidence grading (T1-T4) for each signal
Clinical significance assessment
|
Phase 9: Report Synthesis & Recommendations
Monitoring recommendations
Risk mitigation strategies
Completeness checklist
Phase Summaries
Phase 0: Input Parsing & Drug Disambiguation
Resolve drug name to ChEMBL ID, DrugBank ID. Get mechanism of action, blackbox warning status, targets, and approved indications.
Tools
:
OpenTargets_get_drug_chembId_by_generic_name
,
OpenTargets_get_drug_mechanisms_of_action_by_chemblId
,
OpenTargets_get_drug_blackbox_status_by_chembl_ID
,
drugbank_get_safety_by_drug_name_or_drugbank_id
,
drugbank_get_targets_by_drug_name_or_drugbank_id
,
OpenTargets_get_drug_indications_by_chemblId
Phase 1: FAERS Adverse Event Profiling
Query FAERS for top adverse events, seriousness distribution, outcomes, demographics, and death-related events. Filter serious events by type (death, hospitalization, life-threatening). Get MedDRA hierarchy rollup.
Tools
:
FAERS_count_reactions_by_drug_event
,
FAERS_count_seriousness_by_drug_event
,
FAERS_count_outcomes_by_drug_event
,
FAERS_count_patient_age_distribution
,
FAERS_count_death_related_by_drug
,
FAERS_count_reportercountry_by_drug_event
,
FAERS_filter_serious_events
,
FAERS_rollup_meddra_hierarchy
Phase 2: Disproportionality Analysis (Signal Detection)
CRITICAL PHASE
. For each top adverse event (at least 15-20), calculate PRR, ROR, IC with 95% CI. Classify signal strength. Stratify strong signals by demographics.
Tools
:
FAERS_calculate_disproportionality
,
FAERS_stratify_by_demographics
Signal criteria
PRR >= 2.0 AND lower CI > 1.0 AND N >= 3
Strength
Strong (PRR >= 5), Moderate (PRR 3-5), Weak (PRR 2-3)
See
PHASE_DETAILS.md
for full signal classification table
Phase 3: FDA Label Safety Information
Extract boxed warnings, contraindications, warnings/precautions, adverse reactions, drug interactions, and special population info. Note:
{error: {code: "NOT_FOUND"}}
is normal when a section does not exist.
Tools
:
FDA_get_boxed_warning_info_by_drug_name
,
FDA_get_contraindications_by_drug_name
,
FDA_get_warnings_by_drug_name
,
FDA_get_adverse_reactions_by_drug_name
,
FDA_get_drug_interactions_by_drug_name
,
FDA_get_pregnancy_or_breastfeeding_info_by_drug_name
,
FDA_get_geriatric_use_info_by_drug_name
,
FDA_get_pediatric_use_info_by_drug_name
,
FDA_get_pharmacogenomics_info_by_drug_name
Phase 4: Mechanism-Based Adverse Event Context
Get target safety profile, OpenTargets adverse events, ADMET toxicity predictions (if SMILES available), and drug warnings.
Tools
:
OpenTargets_get_target_safety_profile_by_ensemblID
,
OpenTargets_get_drug_adverse_events_by_chemblId
,
ADMETAI_predict_toxicity
,
ADMETAI_predict_CYP_interactions
,
OpenTargets_get_drug_warnings_by_chemblId
Phase 5: Comparative Safety Analysis
Head-to-head comparison with class members using
FAERS_compare_drugs
. Aggregate class AEs. Identify class-wide vs drug-specific signals.
Tools
:
FAERS_compare_drugs
,
FAERS_count_additive_adverse_reactions
,
FAERS_count_additive_seriousness_classification
Phase 6: Drug-Drug Interactions & Risk Factors
Extract DDIs from FDA label, DrugBank, and DailyMed. Query PharmGKB for pharmacogenomic risk factors and dosing guidelines. Check FDA PGx biomarkers.
Tools
:
FDA_get_drug_interactions_by_drug_name
,
drugbank_get_drug_interactions_by_drug_name_or_id
,
DailyMed_parse_drug_interactions
,
PharmGKB_search_drugs
,
PharmGKB_get_drug_details
,
PharmGKB_get_dosing_guidelines
,
fda_pharmacogenomic_biomarkers
Phase 7: Literature Evidence
Search PubMed, OpenAlex, and EuropePMC for safety studies, case reports, and preprints.
Tools
:
PubMed_search_articles
,
openalex_search_works
,
EuropePMC_search_articles
Phase 8: Risk Assessment & Safety Signal Score
Calculate Safety Signal Score (0-100) from four components: FAERS signal strength (0-35), serious AEs (0-30), FDA label warnings (0-25), literature evidence (0-10). Grade each signal T1-T4. See
PHASE_DETAILS.md
for scoring rubric.
Phase 9: Report Synthesis
Generate comprehensive markdown report with executive summary, all phase outputs, monitoring recommendations, risk mitigation strategies, patient counseling points, and completeness checklist. See
REPORT_TEMPLATE.md
for full template.
Common Analysis Patterns
Pattern
Description
Phases
Full Safety Profile
Comprehensive report for regulatory/safety reviews
All (0-9)
Specific AE Investigation
"Does [drug] cause [event]?"
0, 2, 3, 7
Drug Class Comparison
Compare 3-5 drugs for specific AE
0, 2, 5
Emerging Signal Detection
Screen for signals not in FDA label
1, 2, 3, 7
PGx Risk Assessment
Genetic risk factors for AEs
0, 6
Pre-Approval Assessment
New drugs with limited FAERS data
4, 7
Edge Cases
No FAERS reports
Skip Phases 1-2; rely on FDA label, mechanism predictions, literature
Generic vs Brand name
Try both in FAERS; use
OpenTargets_get_drug_chembId_by_generic_name
to resolve
Drug combinations
Use
FAERS_count_additive_adverse_reactions
for aggregate class analysis
Confounding by indication
Compare AE profile to the disease being treated; note limitation in report
Drugs with boxed warnings
Score component automatically 25/25 for label warnings; prioritize boxed warning events
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