pharma-intelligence-x-6

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原始内容

name: pharma-intelligence description: In-depth, multi-region pharmaceutical intelligence search and synthesis, plus drug repurposing, target discovery, clinical evidence review, and bioactivity analysis. Use this skill whenever the user asks about drug approvals, clinical trials, regulatory submissions, pipeline assets, patent landscapes, competitive intelligence, scientific evidence, disease targets, genetic associations, or compound bioactivity for any drug, target, indication, or company — especially when coverage of China, US, Europe, Japan, South Korea, or Australia is needed. Trigger even for casual queries like "what's the approval status of X in China", "find trials for Y in Japan", "compare pipeline coverage across regions", "find drugs for disease Z", or "what targets are associated with condition W". Always consult this skill before answering any pharma or biomedical research question that requires source-grounded data.

Global Pharma Intelligence & Biomedical Research Skill

Systematic, source-prioritized search and synthesis across regulatory, clinical, academic, and commercial databases — covering all major pharmaceutical markets and 20+ biomedical research databases.

Sub-Skills — How to Invoke

This skill delegates all database work to the sub-skills bundled locally under skills/. Read the relevant sub-skill's SKILL.md before invoking it, then run its bundled script.

See references/sub-skills.md for the full mapping of research tasks to sub-skills and execution patterns.

Core Principle: Tiered Source Priority

Every region follows a 3-tier hierarchy. Higher tiers override lower-tier claims; always cite the tier.

Tier Type Description
Tier 1 Regulatory Official agency submissions, approvals, labels
Tier 2 Trial registries Prospective/registered clinical evidence
Tier 3 Academic / IP Published papers, conferences, patents

For the per-region source map (CN / US / EU / JP / KR / AU + global) with URLs and access notes, see references/sources-by-region.md.

Tool Access Notes

web_fetch is the default tool for any URL in this skill that isn't covered by a bundled sub-skill. Some sites are JavaScript-rendered or block plain HTTP fetches — Google Patents is the most common offender, and CTIS, jRCT, and ANZCTR occasionally behave the same way — but this can happen on any site, not just those.

Rule: try web_fetch first. If it returns empty, blocked, or placeholder content, retry the exact same URL with browser_navigate before concluding that a source has no data. Every other section in this skill that mentions web_fetch defers to this rule rather than restating it.

Search Workflow

Step 1 — Classify the Query (pick ONE intent)

# Intent Trigger phrases
A Trial landscape "trials of X", "clinical studies of", "who is testing", "phase 2/3 of"
B Approval / regulatory status "is X approved", "approval status", "FDA/EMA/NMPA cleared"
C Safety / adverse events "side effects of", "is X safe", "adverse events", "black box"
D Pipeline / competitive intel "pipeline", "competitive landscape", "who else is developing"
E Patent / IP / exclusivity "when does patent expire", "patent landscape", "exclusivity"
F Target / mechanism / drug discovery "drugs targeting X", "mechanism of", "bioactivity", "IC50"
G Repurposing / target discovery "repurpose for", "targets associated with disease", "genetic basis"
H Literature / evidence review "recent papers on", "what's known about", "systematic review"

Also capture: regions in scope (US / EU / JP / CN / KR / AU / global) and time horizon.

Step 2 — Execute the Per-Intent Sequence

Run the workflow for the chosen intent (see Per-Intent Workflows) in order. For sources without MCP coverage (CN NMPA/CDE, EMA EPAR, PMDA, jRCT, CTIS, CRIS, ANZCTR, Orange Book), use web_fetch only at the steps that name them, following the fallback rule in Tool Access Notes.

Resolve identifiers as needed:

  • Free-text disease → MONDO/EFO ID via opentargets-skill or efo-ontology-skill
  • Free-text gene → HGNC symbol via ncbi-clinicaltables-skill or ensembl-skill
  • Cross-database ID conversion → ensembl-skill, uniprot-skill, or efo-ontology-skill

Step 3 — Resolve Conflicts

  1. Higher-tier source wins (Tier 1 > Tier 2 > Tier 3).
  2. More recent data wins within the same tier.
  3. Flag unresolved conflicts; do not silently pick one.

Step 4 — Synthesize and Present

Structure output to match the intent of the question:

  • Trial landscape → table of trials (NCT/registry ID, phase, status, sponsor, N, primary endpoint).
  • Approval status → region × status × date × indications table.
  • Safety → top FAERS reactions plus black-box / warnings.
  • Pipeline → drug × company × phase × mechanism table.
  • Patent → patent number, jurisdiction, expiry.

Always cite source, tier, and access date.

Per-Intent Workflows

A. Trial Landscape

"What clinical studies / trials exist for [drug | target | indication]?"

Default scope = ALL regions. Only narrow if the user names a single region.

clinicaltrials-skill covers only ClinicalTrials.gov, which is primarily US-registered trials. Run each regional source in parallel.

  1. United States — clinicaltrials-skill (action=studies).
    • Use query.intr for a drug, query.cond for a disease, both for combined.
    • For a target/class (e.g., "pan-RAS", "PD-L1 inhibitor"): pass the class term as query.intr plus a relevant query.cond.
    • Then re-run with an NCT ID in query.id for eligibility, endpoints, sponsor, and locations.
  2. China — web_fetch:
    • http://www.chinadrugtrials.org.cn (mandatory CN IND registry)
    • https://www.chictr.org.cn (ChiCTR, WHO primary)
  3. Europe — web_fetch:
    • https://euclinicaltrials.eu (CTIS — current EU register)
    • https://eudract.ema.europa.eu (EudraCT — legacy historical trials)
    • https://www.isrctn.com (ISRCTN, UK/global)
  4. Japan — web_fetch:
    • https://jrct.niph.go.jp (jRCT — mandatory JP registry)
    • https://www.umin.ac.jp/ctr/ (UMIN-CTR — legacy)
  5. South Korea — web_fetch https://cris.nih.go.kr.
  6. Australia / New Zealand — web_fetch https://www.anzctr.org.au.
  7. WHO ICTRP catch-all — web_fetch https://trialsearch.who.int for any WHO primary registry (covers India CTRI, Iran IRCT, Brazil ReBEC, etc.).
  8. Published results — ncbi-entrez-skill (db=pubmed) with NCT ID or drug name to surface completed-trial papers.
  9. US company-disclosed pipeline (optional) — web_fetch SEC EDGAR full-text search at https://efts.sec.gov/LATEST/search-index for US-listed sponsors.

For every regional web_fetch: query both INN and brand name; for CN also use the Chinese transliteration (see references/drug-naming.md). Aggregate results in one table with a "Registry" column.

B. Approval / Regulatory Status

"Is [drug] approved in [region]?"

  1. US — web_fetch https://api.fda.gov/drug/label.json (openFDA) and https://dailymed.nlm.nih.gov/dailymed/services/v2/spls.json (label date anchors approval); web_fetch https://api.fda.gov/drug/ndc.json for orphan status.
  2. Non-US — web_fetch the regional Tier 1 source (NMPA, EMA EPAR, PMDA, MFDS, TGA). For CN, also search Chinese characters.
  3. chembl-skill (drug_indication.json?molecule_chembl_id=...) — cross-check approved indications and max phase.
  4. Say "not approved" only when Tier 1 affirms denial/withdrawal. Otherwise: "no record found as of [date]".

C. Safety / Adverse Events

  1. web_fetch https://api.fda.gov/drug/event.json (FAERS) filtering by drug name and seriousness.
  2. web_fetch https://api.fda.gov/drug/label.json with sections=warnings and sections=contraindications.
  3. chembl-skill (molecule/<id>.json) — inspect the black_box_warning flag.
  4. ncbi-entrez-skill (db=pubmed) with terms "adverse effect" OR "toxicity" for case reports and post-marketing literature.

D. Pipeline / Competitive Intelligence

"Who else is developing for [indication / target]? What's the global competitive landscape?"

Default scope = ALL regions. A competitive landscape without the active-trial picture is incomplete, so run the full multi-region trial sweep from Workflow A and then layer pipeline-specific sources on top.

  1. Active trials — all regions — run Workflow A steps 1–7 in full, optionally adding filter.overallStatus=RECRUITING (or ACTIVE_NOT_RECRUITING) and a phase filter to focus on competitors at a specific stage.
  2. Company disclosures — web_fetch SEC EDGAR full-text search at https://efts.sec.gov/LATEST/search-index for pipeline language in 10-K / 10-Q / 8-K (US-listed sponsors only).
  3. Patent activity per company — web_fetch https://patents.google.com/?assignee=companyname (see Workflow E, step 1, for the exact query format and non-English name handling; or use WIPO PATENTSCOPE / Espacenet as alternatives).
  4. Published results — ncbi-entrez-skill (db=pubmed) with NCT IDs or drug names to surface completed-trial papers.

Aggregate into one table: drug × company × phase × mechanism × registry/region.

E. Patent / IP / Exclusivity

All listed patent sources are free and require no API key.

  1. Global patent search — web_fetch one or more of (see Tool Access Notes for the browser_navigate fallback):
    • https://patents.google.com (Google Patents — best full-text search, covers USPTO, EPO, WIPO, JPO, CNIPA, KIPO). To retrieve all patents assigned to a specific company, query https://patents.google.com/?assignee=companyname. If the company's name is non-English, first search with the original non-English name, then run a second search with the English translation/transliteration — assignee records are not always normalized across languages, so neither search alone is reliable.
    • https://patentscope.wipo.int (WIPO PATENTSCOPE — authoritative for PCT applications and national filings worldwide).
    • https://worldwide.espacenet.com (EPO Espacenet — strongest European and family-tree coverage).
  2. US patents (structured) — uspto_ppubs_search_patents via MCP for granted patents and applications.
  3. Patent family / cross-jurisdiction equivalents — Espacenet's "INPADOC patent family" view, or Google Patents' "Worldwide applications" section.
  4. Orange Book (patent + exclusivity expiry for FDA-approved drugs) — web_fetch https://www.accessdata.fda.gov/scripts/cder/ob.
  5. Orphan exclusivity — fda_orphan_search_exclusivity (7-year US orphan exclusivity).

F. Target / Mechanism / Drug Discovery

  1. chembl-skill — search target/search.json?q=<gene> to resolve target ChEMBL ID, then mechanism.json?target_chembl_id=... for all drugs.
  2. chembl-skill — mechanism.json?molecule_chembl_id=... for mechanism of action of each candidate.
  3. chembl-skill — activity.json?target_chembl_id=... for IC50 / Kd / EC50 bioactivity comparisons.
  4. uniprot-skill — uniprotkb/search with gene:<symbol> AND organism_id:9606 for protein function and druggability context.
  5. reactome-skill — pathway and disease-pathway context for the target.

G. Repurposing / Target Discovery

  1. opentargets-skill — search for disease to resolve MONDO / EFO ID.
  2. opentargets-skill — associatedTargets query with disease EFO ID → ranked targets by evidence score.
  3. gwas-catalog-skill — associations for the disease EFO term to identify genetically supported targets.
  4. web_fetch OMIM API at https://api.omim.org/api/entry/search for Mendelian basis (requires API key).
  5. For each top target: chembl-skill — mechanism.json?target_chembl_id=... for all drugs.
  6. clinicaltrials-skill with each drug as query.intr for prior-art trials.
  7. web_fetch https://api.fda.gov/drug/event.json as a safety filter for non-trivial candidates.

H. Literature / Evidence Review

  1. ncbi-entrez-skill (db=pubmed) — entry point; use MeSH terms for disease, chemical, and gene-aware filtering.
  2. web_fetch Europe PMC REST (https://www.ebi.ac.uk/europepmc/webservices/rest/search) — broader: grants, preprints, non-MEDLINE.
  3. biorxiv-skill — bioRxiv / medRxiv preprints only.
  4. ncbi-pmc-skill or ncbi-entrez-skill (efetch, db=pmc) — abstract or full text for top hits.

Combination Strategies (cross-intent)

Use only when a question genuinely spans multiple intents.

  • Disease → Targets → Drugs → Trials: opentargets-skill (search + associations) → chembl-skill (mechanism by target) → clinicaltrials-skill
  • Gene → Protein → Pathways → Drugs: ncbi-clinicaltables-skill or ensembl-skill → uniprot-skill → reactome-skill → chembl-skill (mechanism by target)
  • Variant → Gene → Disease → Treatments: clinvar-variation-skill or gnomad-graphql-skill → ensembl-skill → opentargets-skill → chembl-skill (mechanism by target)
  • Drug → Safety → Label → Trials: chembl-skill (mechanism) → web_fetch openFDA adverse events → web_fetch openFDA label → clinicaltrials-skill

API Keys

Most APIs require no key. Exceptions:

Database Key Source
OMIM Required https://omim.org/api
NCI Clinical Trials Optional https://clinicaltrialsapi.cancer.gov
OpenFDA Optional (higher rate limits) https://open.fda.gov/apis

All bundled sub-skills (ChEMBL, OpenTargets, PubMed via NCBI Entrez, ClinicalTrials.gov, Reactome, UniProt, GWAS Catalog, Ensembl) are public and require no key. Patent landscape work uses Google Patents, WIPO PATENTSCOPE, and Espacenet — no keys required.

Output Quality Standards

  • Never fabricate approval dates, trial IDs, or efficacy numbers.
  • Attribute every claim to its source and tier.
  • Flag gaps explicitly (e.g., "No registered trials found in jRCT as of [date]").
  • Distinguish "no data found" from "not approved" — absence of evidence ≠ negative regulatory decision.
  • For Chinese sources: note whether the search was conducted in Chinese characters; romanization alone may miss records.

Troubleshooting

No results?

  • Try alternative terms (INN vs brand name, gene symbol vs protein name).
  • Use standardized IDs: MONDO/EFO for diseases, HGNC for genes, ChEMBL IDs for compounds, Ensembl for OpenTargets.
  • Resolve IDs first with efo-ontology-skill, ncbi-clinicaltables-skill, ensembl-skill, or uniprot-skill.

Too many results?

  • Add filters: max_items, filter.phase, filter.overallStatus, reviewed=true (UniProt).
  • Apply date ranges where supported.

API key errors?

  • OMIM requires a key; NCI and OpenFDA accept optional keys for higher rate limits.

Source not covered by a sub-skill?

  • Use web_fetch directly for CDE/NMPA, EMA/EPAR, PMDA, jRCT, CTIS, CRIS, ANZCTR, Orange Book, openFDA, DailyMed, FAERS, and EDGAR.

web_fetch returns empty, blocked, or placeholder content?

  • See Tool Access Notes: retry the same URL with browser_navigate before concluding the source has no data.

References

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