heor-agent-mcp 1.1.0 → 1.2.0

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package/README.md CHANGED
@@ -5,6 +5,8 @@
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  [![node](https://img.shields.io/node/v/heor-agent-mcp.svg)](https://nodejs.org)
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  [![Try in ChatGPT](https://img.shields.io/badge/Try_in-ChatGPT-10A37F?logo=openai&logoColor=white)](https://chatgpt.com/g/g-69f651f588f48191b1d69d54409857ec-heoragent)
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  [![Web UI](https://img.shields.io/badge/Web_UI-Vercel-000000?logo=vercel&logoColor=white)](https://web-michael-ns-projects.vercel.app)
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+ [![EU AI Pact](https://img.shields.io/badge/EU_AI_Pact-Signatory-003399?logo=europeanunion&logoColor=FFCC00)](https://web-michael-ns-projects.vercel.app/ai-transparency)
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+ [![AI Transparency](https://img.shields.io/badge/AI-Transparency_Note-blue)](https://web-michael-ns-projects.vercel.app/ai-transparency)
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  **AI-powered Health Economics and Outcomes Research (HEOR) agent as a Model Context Protocol server.**
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@@ -68,7 +70,7 @@ Add to your MCP configuration:
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  ---
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- ## Tools (20)
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+ ## Tools (21)
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  | Tool | Purpose |
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  |------|---------|
@@ -366,7 +368,7 @@ A companion chat interface is available at:
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  **https://web-michael-ns-projects.vercel.app**
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- - Chat with Claude Sonnet 4.6 + all 20 HEOR tools
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+ - Chat with Claude Sonnet 4.6 + all 21 HEOR tools
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  - **BYOK (Bring Your Own Key)** — paste your Anthropic API key in the settings; it stays in your browser's localStorage and is never stored on our servers
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  - Markdown rendering with styled tables, tool call cards with live progress timers, and theme-aware mermaid network diagrams
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  - 12 example prompts covering literature search, CEA, BIA, NMA, ITC feasibility, RoB, EQ-5D 5L, EU JCA dossiers
@@ -528,6 +530,19 @@ MIT — see [LICENSE](./LICENSE).
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  ---
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+ ## Trust & Transparency
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+ HEORAgent is a **research and analysis tool** — not a clinical decision-support system. It is **not** classified as high-risk under the EU AI Act because it does not drive individual diagnosis, treatment, or monitoring; it falls under limited-risk transparency obligations only. Every output is intended for review by a qualified HEOR/HTA/PV professional before any action is taken.
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+
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+ - **EU AI Pact signatory** — committed to AI governance, high-risk system mapping, and AI literacy promotion (voluntary commitments per the European Commission, ahead of the AI Act's August 2026 deadline).
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+ - **PRISMA-style audit trail** on every tool call (sources queried, succeeded, failed, assumptions applied).
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+ - **AI commentary explicitly labelled** — domain claims (ICERs, trial results, regulatory decisions) come exclusively from tool outputs, never from training-data recall.
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+ - **Methodology cited inline** — ISPOR, NICE DSU TSDs, NICE PMG36, Cochrane Handbook, GRADE, EMA GVP, Cope 2014, Phillippo 2016, Biz 2026.
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+ Full statement: **[/ai-transparency](https://web-michael-ns-projects.vercel.app/ai-transparency)** — risk classification, human oversight model, methodological references, and reporting channel.
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+
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+ ---
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+
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  ## Disclaimer
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  **All outputs are preliminary and for research orientation only.** Results require validation by a qualified health economist before use in any HTA submission, payer negotiation, regulatory filing, or clinical decision. This tool does not replace professional HEOR expertise.
@@ -0,0 +1,21 @@
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+ /**
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+ * Country profiles for the EU JCA PICO matrix analyzer (design log #13).
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+ * Source of truth: latest available G-BA / HAS / AIFA / RedETS /
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+ * Zorginstituut / NICE clinical-practice and HTA recommendations as of
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+ * Q2 2026.
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+ *
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+ * Comparator lookups are coarse — molecule name + 1-line rationale only.
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+ * Bumped via JCA_REVISION when EUnetHTA publishes new methodological
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+ * guidance or country preferences change materially.
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+ */
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+ import type { CountryProfile, IndicationCategory, Jurisdiction, OutcomePriority } from "./types.js";
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+ export declare const JCA_REVISION: "2026-05";
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+ export declare const COUNTRY_PROFILES: Record<Jurisdiction, CountryProfile>;
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+ /**
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+ * Coarse classifier mapping a free-text indication to a category.
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+ * Errs on "other" rather than guessing wrong.
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+ */
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+ export declare function classifyIndication(indication: string): IndicationCategory;
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+ export declare function profileFor(jurisdiction: Jurisdiction): CountryProfile;
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+ export declare function outcomePriorityForCategory(category: IndicationCategory): OutcomePriority[];
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+ //# sourceMappingURL=countryRegistry.d.ts.map
@@ -0,0 +1 @@
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+ {"version":3,"file":"countryRegistry.d.ts","sourceRoot":"","sources":["../../src/jca/countryRegistry.ts"],"names":[],"mappings":"AAAA;;;;;;;;;GASG;AACH,OAAO,KAAK,EAEV,cAAc,EAEd,kBAAkB,EAClB,YAAY,EAEZ,eAAe,EAChB,MAAM,YAAY,CAAC;AAEpB,eAAO,MAAM,YAAY,EAAG,SAAkB,CAAC;AAuL/C,eAAO,MAAM,gBAAgB,EAAE,MAAM,CAAC,YAAY,EAAE,cAAc,CAsBjE,CAAC;AAEF;;;GAGG;AACH,wBAAgB,kBAAkB,CAAC,UAAU,EAAE,MAAM,GAAG,kBAAkB,CAoDzE;AAED,wBAAgB,UAAU,CAAC,YAAY,EAAE,YAAY,GAAG,cAAc,CAErE;AAED,wBAAgB,0BAA0B,CACxC,QAAQ,EAAE,kBAAkB,GAC3B,eAAe,EAAE,CAEnB"}
@@ -0,0 +1,248 @@
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+ export const JCA_REVISION = "2026-05";
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+ function instrumentsFor(category) {
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+ if (category === "oncology_nsclc" || category === "oncology_other") {
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+ return ["EQ-5D-5L", "EORTC QLQ-C30"];
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+ }
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+ if (category === "ibd_uc" || category === "ibd_cd") {
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+ return ["EQ-5D-5L", "IBDQ-32"];
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+ }
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+ if (category === "diabetes_t2" || category === "obesity") {
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+ return ["EQ-5D-5L", "IWQOL-Lite"];
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+ }
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+ return ["EQ-5D-5L"];
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+ }
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+ function oncologyOutcomePriority() {
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+ return ["OS", "PFS", "HRQoL", "AE"];
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+ }
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+ function ibdOutcomePriority() {
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+ return ["remission", "HRQoL", "AE", "other"];
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+ }
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+ function chronicOutcomePriority() {
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+ return ["HRQoL", "remission", "AE", "other"];
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+ }
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+ function outcomePriorityFor(category) {
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+ if (category === "oncology_nsclc" || category === "oncology_other") {
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+ return oncologyOutcomePriority();
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+ }
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+ if (category === "ibd_uc" || category === "ibd_cd") {
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+ return ibdOutcomePriority();
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+ }
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+ return chronicOutcomePriority();
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+ }
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+ function nsclcSecondLineComparators(country) {
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+ // NSCLC 2L EGFR-mutant: chemo doublet (carboplatin + pemetrexed) is
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+ // standard everywhere; immunotherapy (pembrolizumab/nivolumab) is the
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+ // alternative in DE/NL; ramucirumab + erlotinib is more common in IT/ES.
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+ const instruments = instrumentsFor("oncology_nsclc");
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+ const chemo = {
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+ molecule: "carboplatin + pemetrexed",
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+ rationale: `Chemotherapy doublet — standard 2L NSCLC backbone in ${country.toUpperCase()} per local clinical guidelines.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ const io = {
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+ molecule: "pembrolizumab",
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+ rationale: `Immunotherapy — frequently considered as comparator for 2L NSCLC where PD-L1 status supports it. Recognised in ${country.toUpperCase()} HTA submissions.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ const tki_alt = {
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+ molecule: "afatinib",
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+ rationale: `Alternative TKI option in EGFR-mutant 2L; relevant context comparator in ${country.toUpperCase()}.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ if (country === "de" || country === "nl")
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+ return [chemo, io];
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+ if (country === "fr")
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+ return [chemo, tki_alt];
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+ if (country === "it" || country === "es")
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+ return [chemo, io, tki_alt];
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+ if (country === "uk")
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+ return [chemo, io];
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+ return [chemo];
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+ }
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+ function ibdUcBiologicComparators(country) {
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+ const instruments = instrumentsFor("ibd_uc");
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+ // UC biologics universe (post-2024): vedolizumab, infliximab, ustekinumab,
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+ // mirikizumab, ozanimod. National HTA preferences vary.
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+ const ved = {
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+ molecule: "vedolizumab",
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+ rationale: `Gut-selective integrin inhibitor — established 1L biologic in ${country.toUpperCase()} for moderate-to-severe UC.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ const ifx = {
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+ molecule: "infliximab",
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+ rationale: `Anti-TNF — historical UC standard; biosimilar pricing keeps it as a comparator anchor in ${country.toUpperCase()}.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ const ust = {
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+ molecule: "ustekinumab",
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+ rationale: `IL-12/23 inhibitor — recognised UC biologic option.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ const oz = {
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+ molecule: "ozanimod",
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+ rationale: `S1P receptor modulator — oral option, increasingly considered in 1L moderate UC.`,
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+ outcome_instrument_preferences: instruments,
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+ };
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+ if (country === "de")
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+ return [ved, ifx, ust];
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+ if (country === "fr")
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+ return [ved, ifx, oz];
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+ if (country === "it" || country === "es")
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+ return [ved, ifx, ust, oz];
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+ if (country === "nl")
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+ return [ved, ust];
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+ if (country === "uk")
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+ return [ved, ifx, ust];
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+ return [ved, ifx];
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+ }
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+ function genericComparators(country, category) {
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+ const instruments = instrumentsFor(category);
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+ return [
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+ {
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+ molecule: "standard of care (country-specific)",
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+ rationale: `Coarse placeholder — confirm against latest ${country.toUpperCase()} HTA precedents and clinical guidelines.`,
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+ outcome_instrument_preferences: instruments,
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+ },
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+ ];
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+ }
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+ function comparatorsFor(country, category, drug_class, line) {
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+ if (category === "oncology_nsclc" && line === "second_line") {
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+ return nsclcSecondLineComparators(country);
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+ }
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+ if (category === "ibd_uc") {
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+ return ibdUcBiologicComparators(country);
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+ }
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+ // Drug-class-aware fallback for unknown indications
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+ if (category === "oncology_other" || category === "oncology_nsclc") {
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+ const instruments = instrumentsFor(category);
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+ return [
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+ {
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+ molecule: "standard chemotherapy doublet",
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+ rationale: `Default oncology comparator anchor for ${country.toUpperCase()}; refine against the indication's clinical trial protocol.`,
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+ outcome_instrument_preferences: instruments,
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+ },
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+ ];
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+ }
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+ void drug_class;
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+ return genericComparators(country, category);
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+ }
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+ function subgroupsFor(category) {
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+ if (category === "oncology_nsclc") {
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+ return [
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+ "EGFR mutation status",
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+ "PD-L1 TPS (≥50% / 1-49% / <1%)",
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+ "ECOG performance status (0-1 vs 2)",
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+ "brain metastases (yes/no)",
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+ ];
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+ }
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+ if (category === "ibd_uc") {
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+ return [
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+ "Mayo total score (moderate vs severe)",
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+ "prior biologic exposure (TNF-experienced vs naive)",
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+ "extent of colitis (left-sided vs extensive)",
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+ ];
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+ }
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+ if (category === "ibd_cd") {
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+ return [
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+ "CDAI (moderate vs severe)",
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+ "prior biologic exposure",
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+ "fistulizing vs luminal disease",
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+ ];
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+ }
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+ if (category === "diabetes_t2") {
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+ return ["baseline HbA1c", "BMI category", "CV risk status"];
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+ }
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+ if (category === "obesity") {
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+ return ["BMI category", "comorbidities (T2D, CV, OSA)"];
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+ }
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+ return ["age strata", "comorbidity status"];
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+ }
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+ function profile(jurisdiction, hta_body) {
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+ return {
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+ jurisdiction,
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+ hta_body,
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+ outcome_instrument_preferences: ["EQ-5D-5L"],
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+ outcome_priority: ["OS", "PFS", "HRQoL", "AE"],
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+ comparators: (cat, dc, line) => comparatorsFor(jurisdiction, cat, dc, line),
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+ population_subgroups: (cat) => subgroupsFor(cat),
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+ };
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+ }
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+ export const COUNTRY_PROFILES = {
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+ de: profile("de", "G-BA / IQWiG"),
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+ fr: profile("fr", "HAS"),
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+ it: profile("it", "AIFA"),
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+ es: profile("es", "AEMPS / RedETS"),
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+ nl: profile("nl", "Zorginstituut Nederland"),
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+ uk: profile("uk", "NICE (post-Brexit, context only)"),
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+ eu_other: {
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+ jurisdiction: "eu_other",
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+ hta_body: "Other EU member states — consult national HTA",
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+ outcome_instrument_preferences: ["EQ-5D-5L"],
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+ outcome_priority: ["OS", "PFS", "HRQoL", "AE"],
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+ comparators: () => [
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+ {
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+ molecule: "consult national HTA body",
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+ rationale: "v1 of jca_pico_scope covers DE/FR/IT/ES/NL + UK only. For other EU member states (BE, AT, SE, DK, FI, PL, CZ, HU, etc.), consult the national HTA body for jurisdiction-specific comparator preferences.",
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+ outcome_instrument_preferences: ["EQ-5D-5L"],
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+ },
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+ ],
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+ population_subgroups: () => [],
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+ },
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+ };
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+ /**
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+ * Coarse classifier mapping a free-text indication to a category.
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+ * Errs on "other" rather than guessing wrong.
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+ */
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+ export function classifyIndication(indication) {
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+ const x = indication.toLowerCase();
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+ if (x.includes("nsclc") ||
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+ x.includes("non-small cell lung") ||
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+ x.includes("lung cancer")) {
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+ return "oncology_nsclc";
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+ }
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+ if (x.includes("cancer") ||
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+ x.includes("oncolog") ||
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+ x.includes("carcinoma") ||
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+ x.includes("tumour") ||
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+ x.includes("tumor") ||
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+ x.includes("myeloma") ||
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+ x.includes("leukemia") ||
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+ x.includes("leukaemia") ||
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+ x.includes("lymphoma")) {
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+ return "oncology_other";
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+ }
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+ if (x.includes("ulcerative colitis") || x.includes("uc"))
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+ return "ibd_uc";
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+ if (x.includes("crohn"))
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+ return "ibd_cd";
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+ if (x.includes("type 2 diabetes") || x.includes("t2d") || x.includes("diabetes mellitus type 2")) {
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+ return "diabetes_t2";
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+ }
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+ if (x.includes("obesity") || x.includes("overweight"))
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+ return "obesity";
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+ if (x.includes("cardiovascular") ||
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+ x.includes("heart failure") ||
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+ x.includes("hypertension")) {
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+ return "cardiovascular";
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+ }
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+ if (x.includes("rheumatoid") ||
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+ x.includes("psoriatic") ||
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+ x.includes("ankylosing") ||
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+ x.includes("lupus")) {
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+ return "rheumatology";
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+ }
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+ if (x.includes("multiple sclerosis") ||
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+ x.includes("alzheimer") ||
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+ x.includes("parkinson") ||
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+ x.includes("epilepsy")) {
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+ return "neurology";
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+ }
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+ return "other";
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+ }
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+ export function profileFor(jurisdiction) {
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+ return COUNTRY_PROFILES[jurisdiction];
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+ }
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+ export function outcomePriorityForCategory(category) {
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+ return outcomePriorityFor(category);
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+ }
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+ //# sourceMappingURL=countryRegistry.js.map
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1
+ 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@@ -0,0 +1,15 @@
1
+ import type { ComparatorEntry, DrugClass, Jurisdiction, LineOfTherapy, PicoMatrix } from "./types.js";
2
+ export interface ScopeBuilderInput {
3
+ drug: string;
4
+ indication: string;
5
+ drug_class: DrugClass;
6
+ mechanism_of_action?: string;
7
+ line_of_therapy: LineOfTherapy;
8
+ biomarker_status?: string;
9
+ jurisdictions: Jurisdiction[];
10
+ regulatory_context: "pre_authorisation" | "post_authorisation" | "conditional_approval";
11
+ }
12
+ export declare function buildScope(input: ScopeBuilderInput): PicoMatrix;
13
+ /** Lists every comparator molecule a country profile produced — used for the markdown report. */
14
+ export declare function flattenComparators(country_specific: PicoMatrix["country_specific"]): ComparatorEntry[];
15
+ //# sourceMappingURL=scopeBuilder.d.ts.map
@@ -0,0 +1 @@
1
+ {"version":3,"file":"scopeBuilder.d.ts","sourceRoot":"","sources":["../../src/jca/scopeBuilder.ts"],"names":[],"mappings":"AAUA,OAAO,KAAK,EACV,eAAe,EACf,SAAS,EACT,YAAY,EACZ,aAAa,EACb,UAAU,EACX,MAAM,YAAY,CAAC;AAEpB,MAAM,WAAW,iBAAiB;IAChC,IAAI,EAAE,MAAM,CAAC;IACb,UAAU,EAAE,MAAM,CAAC;IACnB,UAAU,EAAE,SAAS,CAAC;IACtB,mBAAmB,CAAC,EAAE,MAAM,CAAC;IAC7B,eAAe,EAAE,aAAa,CAAC;IAC/B,gBAAgB,CAAC,EAAE,MAAM,CAAC;IAC1B,aAAa,EAAE,YAAY,EAAE,CAAC;IAC9B,kBAAkB,EACd,mBAAmB,GACnB,oBAAoB,GACpB,sBAAsB,CAAC;CAC5B;AAED,wBAAgB,UAAU,CAAC,KAAK,EAAE,iBAAiB,GAAG,UAAU,CAqC/D;AA2DD,iGAAiG;AACjG,wBAAgB,kBAAkB,CAChC,gBAAgB,EAAE,UAAU,CAAC,kBAAkB,CAAC,GAC/C,eAAe,EAAE,CAInB"}
@@ -0,0 +1,89 @@
1
+ /**
2
+ * Pure scope-builder logic for jca_pico_scope. Given a normalised input,
3
+ * returns a fully-populated PicoMatrix without any I/O. See design log #13.
4
+ */
5
+ import { classifyIndication, JCA_REVISION, outcomePriorityForCategory, profileFor, } from "./countryRegistry.js";
6
+ export function buildScope(input) {
7
+ const category = classifyIndication(input.indication);
8
+ const country_specific = input.jurisdictions.map((j) => {
9
+ const p = profileFor(j);
10
+ const comparators = p.comparators(category, input.drug_class, input.line_of_therapy);
11
+ return {
12
+ jurisdiction: j,
13
+ hta_body: p.hta_body,
14
+ comparators,
15
+ population_subgroups: p.population_subgroups(category),
16
+ outcome_priorities: outcomePriorityForCategory(category),
17
+ };
18
+ });
19
+ const distinctMolecules = new Set();
20
+ for (const c of country_specific) {
21
+ for (const cmp of c.comparators)
22
+ distinctMolecules.add(cmp.molecule);
23
+ }
24
+ const distinct_comparator_count = distinctMolecules.size;
25
+ const heterogeneity_warning = input.jurisdictions.length > 1 && distinct_comparator_count >= 3;
26
+ const picos = buildPicos(input, country_specific);
27
+ const rationale = buildRationale(input, category, distinct_comparator_count);
28
+ return {
29
+ drug: input.drug,
30
+ indication: input.indication,
31
+ jca_revision: JCA_REVISION,
32
+ picos,
33
+ country_specific,
34
+ heterogeneity_warning,
35
+ distinct_comparator_count,
36
+ rationale,
37
+ };
38
+ }
39
+ function buildPicos(input, country_specific) {
40
+ const seen = new Set();
41
+ const picos = [];
42
+ let counter = 1;
43
+ const populationBase = input.biomarker_status
44
+ ? `${input.indication}; biomarker: ${input.biomarker_status}`
45
+ : input.indication;
46
+ for (const country of country_specific) {
47
+ for (const cmp of country.comparators) {
48
+ const key = `${cmp.molecule}::${country.outcome_priorities.join(",")}`;
49
+ if (seen.has(key))
50
+ continue;
51
+ seen.add(key);
52
+ picos.push({
53
+ id: `PICO-${counter}`,
54
+ population: populationBase,
55
+ comparator: cmp.molecule,
56
+ outcomes: country.outcome_priorities.map((o) => o.toString()),
57
+ });
58
+ counter += 1;
59
+ }
60
+ }
61
+ if (picos.length === 0) {
62
+ picos.push({
63
+ id: "PICO-1",
64
+ population: populationBase,
65
+ comparator: "standard of care",
66
+ outcomes: ["clinical effectiveness", "HRQoL", "AE"],
67
+ });
68
+ }
69
+ return picos;
70
+ }
71
+ function buildRationale(input, category, distinct) {
72
+ const parts = [];
73
+ parts.push(`JCA scope for ${input.drug} in ${input.indication} (${category} category) across ${input.jurisdictions.length} jurisdiction(s).`);
74
+ if (input.regulatory_context === "pre_authorisation") {
75
+ parts.push("Anticipatory scope — JCA scope is finalised at marketing authorisation; this output is for protocol-design and pre-MA market access strategy only.");
76
+ }
77
+ if (distinct >= 3) {
78
+ parts.push(`Heterogeneity warning: ${distinct} distinct comparator molecules across jurisdictions. Plan for evidence_network + itc_feasibility before estimation.`);
79
+ }
80
+ return parts.join(" ");
81
+ }
82
+ /** Lists every comparator molecule a country profile produced — used for the markdown report. */
83
+ export function flattenComparators(country_specific) {
84
+ const out = [];
85
+ for (const c of country_specific)
86
+ out.push(...c.comparators);
87
+ return out;
88
+ }
89
+ //# sourceMappingURL=scopeBuilder.js.map
@@ -0,0 +1 @@
1
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@@ -0,0 +1,41 @@
1
+ export type Jurisdiction = "de" | "fr" | "it" | "es" | "nl" | "uk" | "eu_other";
2
+ export type DrugClass = "monoclonal_antibody" | "small_molecule" | "atmp_cell" | "atmp_gene" | "atmp_tissue" | "biosimilar" | "vaccine" | "radiopharmaceutical" | "other";
3
+ export type LineOfTherapy = "first_line" | "second_line" | "third_line_plus" | "any";
4
+ export type OutcomePriority = "OS" | "PFS" | "HRQoL" | "AE" | "remission" | "other";
5
+ export interface ComparatorEntry {
6
+ molecule: string;
7
+ rationale: string;
8
+ outcome_instrument_preferences: string[];
9
+ }
10
+ export interface CountryProfile {
11
+ jurisdiction: Jurisdiction;
12
+ hta_body: string;
13
+ outcome_instrument_preferences: string[];
14
+ outcome_priority: OutcomePriority[];
15
+ /** Pure function — given a drug-class and indication category, returns the comparator universe for this country. */
16
+ comparators: (indication_category: IndicationCategory, drug_class: DrugClass, line: LineOfTherapy) => ComparatorEntry[];
17
+ population_subgroups: (indication_category: IndicationCategory) => string[];
18
+ }
19
+ export type IndicationCategory = "oncology_nsclc" | "oncology_other" | "ibd_uc" | "ibd_cd" | "diabetes_t2" | "obesity" | "cardiovascular" | "rheumatology" | "neurology" | "rare_disease" | "infectious_disease" | "other";
20
+ export interface PicoMatrix {
21
+ drug: string;
22
+ indication: string;
23
+ jca_revision: "2026-05";
24
+ picos: Array<{
25
+ id: string;
26
+ population: string;
27
+ comparator: string;
28
+ outcomes: string[];
29
+ }>;
30
+ country_specific: Array<{
31
+ jurisdiction: Jurisdiction;
32
+ hta_body: string;
33
+ comparators: ComparatorEntry[];
34
+ population_subgroups: string[];
35
+ outcome_priorities: OutcomePriority[];
36
+ }>;
37
+ heterogeneity_warning: boolean;
38
+ distinct_comparator_count: number;
39
+ rationale: string;
40
+ }
41
+ //# sourceMappingURL=types.d.ts.map
@@ -0,0 +1 @@
1
+ {"version":3,"file":"types.d.ts","sourceRoot":"","sources":["../../src/jca/types.ts"],"names":[],"mappings":"AAAA,MAAM,MAAM,YAAY,GAAG,IAAI,GAAG,IAAI,GAAG,IAAI,GAAG,IAAI,GAAG,IAAI,GAAG,IAAI,GAAG,UAAU,CAAC;AAEhF,MAAM,MAAM,SAAS,GACjB,qBAAqB,GACrB,gBAAgB,GAChB,WAAW,GACX,WAAW,GACX,aAAa,GACb,YAAY,GACZ,SAAS,GACT,qBAAqB,GACrB,OAAO,CAAC;AAEZ,MAAM,MAAM,aAAa,GACrB,YAAY,GACZ,aAAa,GACb,iBAAiB,GACjB,KAAK,CAAC;AAEV,MAAM,MAAM,eAAe,GAAG,IAAI,GAAG,KAAK,GAAG,OAAO,GAAG,IAAI,GAAG,WAAW,GAAG,OAAO,CAAC;AAEpF,MAAM,WAAW,eAAe;IAC9B,QAAQ,EAAE,MAAM,CAAC;IACjB,SAAS,EAAE,MAAM,CAAC;IAClB,8BAA8B,EAAE,MAAM,EAAE,CAAC;CAC1C;AAED,MAAM,WAAW,cAAc;IAC7B,YAAY,EAAE,YAAY,CAAC;IAC3B,QAAQ,EAAE,MAAM,CAAC;IACjB,8BAA8B,EAAE,MAAM,EAAE,CAAC;IACzC,gBAAgB,EAAE,eAAe,EAAE,CAAC;IACpC,oHAAoH;IACpH,WAAW,EAAE,CACX,mBAAmB,EAAE,kBAAkB,EACvC,UAAU,EAAE,SAAS,EACrB,IAAI,EAAE,aAAa,KAChB,eAAe,EAAE,CAAC;IACvB,oBAAoB,EAAE,CAAC,mBAAmB,EAAE,kBAAkB,KAAK,MAAM,EAAE,CAAC;CAC7E;AAED,MAAM,MAAM,kBAAkB,GAC1B,gBAAgB,GAChB,gBAAgB,GAChB,QAAQ,GACR,QAAQ,GACR,aAAa,GACb,SAAS,GACT,gBAAgB,GAChB,cAAc,GACd,WAAW,GACX,cAAc,GACd,oBAAoB,GACpB,OAAO,CAAC;AAEZ,MAAM,WAAW,UAAU;IACzB,IAAI,EAAE,MAAM,CAAC;IACb,UAAU,EAAE,MAAM,CAAC;IACnB,YAAY,EAAE,SAAS,CAAC;IACxB,KAAK,EAAE,KAAK,CAAC;QACX,EAAE,EAAE,MAAM,CAAC;QACX,UAAU,EAAE,MAAM,CAAC;QACnB,UAAU,EAAE,MAAM,CAAC;QACnB,QAAQ,EAAE,MAAM,EAAE,CAAC;KACpB,CAAC,CAAC;IACH,gBAAgB,EAAE,KAAK,CAAC;QACtB,YAAY,EAAE,YAAY,CAAC;QAC3B,QAAQ,EAAE,MAAM,CAAC;QACjB,WAAW,EAAE,eAAe,EAAE,CAAC;QAC/B,oBAAoB,EAAE,MAAM,EAAE,CAAC;QAC/B,kBAAkB,EAAE,eAAe,EAAE,CAAC;KACvC,CAAC,CAAC;IACH,qBAAqB,EAAE,OAAO,CAAC;IAC/B,yBAAyB,EAAE,MAAM,CAAC;IAClC,SAAS,EAAE,MAAM,CAAC;CACnB"}
@@ -0,0 +1,2 @@
1
+ export {};
2
+ //# sourceMappingURL=types.js.map
@@ -0,0 +1 @@
1
+ {"version":3,"file":"types.js","sourceRoot":"","sources":["../../src/jca/types.ts"],"names":[],"mappings":""}
@@ -110,6 +110,18 @@ export interface DossierParams {
110
110
  }>;
111
111
  /** Optional structured PV classification from pv_classify — when provided, populates the Pharmacovigilance Plan section. */
112
112
  pv_classification?: any;
113
+ /** NICE PMG36 severity modifier inputs (replaces end-of-life modifier as of April 2022). */
114
+ severity_modifier?: {
115
+ absolute_qaly_shortfall?: number;
116
+ proportional_qaly_shortfall?: number;
117
+ };
118
+ /** Health inequalities evidence per NICE PMG36 May 2025 modular update. */
119
+ health_inequalities?: {
120
+ affected_groups: string[];
121
+ baseline_disparity_evidence?: string;
122
+ intervention_impact: "narrows" | "neutral" | "widens" | "unknown";
123
+ mitigation_plan?: string;
124
+ };
113
125
  }
114
126
  export interface ToolResult {
115
127
  content: string | object;
@@ -1 +1 @@
1
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package/dist/server.js CHANGED
@@ -28,6 +28,7 @@ import { handleItcFeasibility, itcFeasibilityToolSchema, } from "./tools/itcFeas
28
28
  import { handleExamples, examplesToolSchema } from "./tools/examples.js";
29
29
  import { handleMaicWorkflow, maicWorkflowToolSchema, } from "./tools/maicWorkflow.js";
30
30
  import { handlePvClassify, pvClassifyToolSchema } from "./tools/pvClassify.js";
31
+ import { handleJcaPicoScope, jcaPicoScopeToolSchema, } from "./tools/jcaPicoScope.js";
31
32
  import { randomUUID } from "node:crypto";
32
33
  import { trackToolCall, trackSession, shutdownAnalytics, inferSurface, } from "./analytics.js";
33
34
  import { createServer } from "node:http";
@@ -160,6 +161,7 @@ function createMcpServer(surfaceRef = { value: "direct_mcp" }, sessionIdRef = {
160
161
  examplesToolSchema,
161
162
  maicWorkflowToolSchema,
162
163
  pvClassifyToolSchema,
164
+ jcaPicoScopeToolSchema,
163
165
  ],
164
166
  }));
165
167
  server.setRequestHandler(CallToolRequestSchema, async (request) => {
@@ -228,6 +230,9 @@ function createMcpServer(surfaceRef = { value: "direct_mcp" }, sessionIdRef = {
228
230
  case "pv.classify":
229
231
  result = await handlePvClassify(args);
230
232
  break;
233
+ case "jca.pico_scope":
234
+ result = await handleJcaPicoScope(args);
235
+ break;
231
236
  default:
232
237
  trackToolCall(name, Date.now() - callStart, "error", sessionIdRef.value || undefined, {
233
238
  surface: surfaceRef.value,
@@ -1 +1 @@
1
- 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1
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@@ -1 +1 @@
1
- {"version":3,"file":"htaDossierPrep.d.ts","sourceRoot":"","sources":["../../src/tools/htaDossierPrep.ts"],"names":[],"mappings":"AACA,OAAO,KAAK,EAEV,UAAU,EAGX,MAAM,uBAAuB,CAAC;AAuwB/B,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CAqJrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAyFpC,CAAC"}
1
+ {"version":3,"file":"htaDossierPrep.d.ts","sourceRoot":"","sources":["../../src/tools/htaDossierPrep.ts"],"names":[],"mappings":"AACA,OAAO,KAAK,EAEV,UAAU,EAGX,MAAM,uBAAuB,CAAC;AAw4B/B,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CA0JrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAyFpC,CAAC"}
@@ -42,6 +42,24 @@ const DossierSchema = z.object({
42
42
  }))
43
43
  .optional()
44
44
  .describe("Optional: GRADE upgrading flags per outcome for observational evidence (Guyatt 2011). 'large_effect' rates effect magnitude (large=RR<0.5 or >2.0; very_large=RR<0.2 or >5.0). 'dose_response' = documented gradient. 'plausible_confounding_toward_null' = bias would reduce effect. Capped at +2 steps. Ignored for RCT evidence (already High)."),
45
+ severity_modifier: z
46
+ .object({
47
+ absolute_qaly_shortfall: z.number().min(0).optional(),
48
+ proportional_qaly_shortfall: z.number().min(0).max(1).optional(),
49
+ })
50
+ .optional()
51
+ .describe("NICE PMG36 severity modifier inputs (replaced the end-of-life modifier in April 2022 in opportunity-cost-neutral form). Provide either absolute QALY shortfall (years), proportional shortfall (0-1), or both. Modifier weight is the higher of the two: <12 absolute and <0.85 proportional → 1.0×; 12-18 or 0.85-0.95 → 1.2×; ≥18 or ≥0.95 → 1.7×."),
52
+ health_inequalities: z
53
+ .object({
54
+ affected_groups: z.array(z.string()).default([]),
55
+ baseline_disparity_evidence: z.string().optional(),
56
+ intervention_impact: z
57
+ .enum(["narrows", "neutral", "widens", "unknown"])
58
+ .default("unknown"),
59
+ mitigation_plan: z.string().optional(),
60
+ })
61
+ .optional()
62
+ .describe("Health inequalities evidence per the NICE PMG36 May 2025 modular update. List affected populations, baseline disparity evidence, and the intervention's expected impact on inequality (narrows/neutral/widens). Required by NICE for any intervention that affects disadvantaged groups."),
45
63
  pv_classification: z
46
64
  .object({
47
65
  primary_category: z.enum([
@@ -158,6 +176,83 @@ const METHODOLOGY_BY_BODY = {
158
176
  jca: "EUHTA Regulation (EU) 2021/2282 — Joint Clinical Assessment",
159
177
  gvd: "Global Value Dossier — cross-market foundational evidence document (ISPOR GVD best practices)",
160
178
  };
179
+ /**
180
+ * NICE PMG36 severity modifier weight per absolute and proportional QALY
181
+ * shortfall. The higher of the two thresholds wins. Replaced the
182
+ * end-of-life modifier in April 2022 in opportunity-cost-neutral form.
183
+ */
184
+ function severityModifierWeight(absolute, proportional) {
185
+ const weights = [1.0];
186
+ if ((absolute ?? 0) >= 12 || (proportional ?? 0) >= 0.85)
187
+ weights.push(1.2);
188
+ if ((absolute ?? 0) >= 18 || (proportional ?? 0) >= 0.95)
189
+ weights.push(1.7);
190
+ const weight = weights[weights.length - 1];
191
+ if (weight === 1.7)
192
+ return { weight, band: "Severe" };
193
+ if (weight === 1.2)
194
+ return { weight, band: "Moderate" };
195
+ return { weight: 1.0, band: "No modifier" };
196
+ }
197
+ function appendSeverityModifierSection(lines, sm) {
198
+ if (!sm)
199
+ return;
200
+ const { weight, band } = severityModifierWeight(sm.absolute_qaly_shortfall, sm.proportional_qaly_shortfall);
201
+ lines.push("## Severity Modifier (NICE PMG36)");
202
+ lines.push(`**Replaced the end-of-life modifier in April 2022** in an opportunity-cost-neutral form (PMG36 §4.4).`);
203
+ if (sm.absolute_qaly_shortfall !== undefined) {
204
+ lines.push(`- Absolute QALY shortfall: **${sm.absolute_qaly_shortfall.toFixed(1)} QALYs**`);
205
+ }
206
+ if (sm.proportional_qaly_shortfall !== undefined) {
207
+ lines.push(`- Proportional QALY shortfall: **${(sm.proportional_qaly_shortfall * 100).toFixed(0)}%**`);
208
+ }
209
+ lines.push("");
210
+ lines.push(`**Severity band:** ${band}`);
211
+ lines.push(`**QALY weight applied:** ×${weight.toFixed(1)}`);
212
+ lines.push("");
213
+ lines.push("Effective WTP threshold = nominal WTP × QALY weight. With the standard NICE £20-30K/QALY threshold this yields:");
214
+ lines.push("");
215
+ lines.push("| Band | Weight | Effective £/QALY threshold |");
216
+ lines.push("|------|--------|----------------------------|");
217
+ lines.push("| No modifier | ×1.0 | £20,000-30,000 |");
218
+ lines.push("| Moderate | ×1.2 | £24,000-36,000 |");
219
+ lines.push("| Severe | ×1.7 | £34,000-51,000 |");
220
+ lines.push("");
221
+ }
222
+ function appendHealthInequalitiesSection(lines, hi) {
223
+ lines.push("## Health Inequalities (NICE PMG36 May 2025 update)");
224
+ if (!hi) {
225
+ lines.push("*Health Inequalities not provided. NICE's May 2025 inequalities methods update requires evidence on whether the technology narrows, leaves unchanged, or widens disparities for affected populations. Add `health_inequalities` to the dossier inputs to populate this section.*");
226
+ lines.push("");
227
+ return;
228
+ }
229
+ lines.push(`*Per NICE PMG36 May 2025 modular update on the approach to providing evidence on the impact of health inequalities.*`);
230
+ lines.push("");
231
+ if (hi.affected_groups.length > 0) {
232
+ lines.push("**Affected groups:**");
233
+ for (const g of hi.affected_groups)
234
+ lines.push(`- ${g}`);
235
+ lines.push("");
236
+ }
237
+ if (hi.baseline_disparity_evidence) {
238
+ lines.push("**Baseline disparity evidence:**");
239
+ lines.push(`> ${hi.baseline_disparity_evidence}`);
240
+ lines.push("");
241
+ }
242
+ const impactLabels = {
243
+ narrows: "✅ **Narrows** — intervention reduces disparity",
244
+ neutral: "⚪ **Neutral** — intervention does not change disparity",
245
+ widens: "⚠️ **Widens** — intervention increases disparity (warning)",
246
+ unknown: "❓ **Unknown** — disparity impact not assessed",
247
+ };
248
+ lines.push(`**Intervention impact:** ${impactLabels[hi.intervention_impact]}`);
249
+ lines.push("");
250
+ if (hi.mitigation_plan) {
251
+ lines.push("**Mitigation plan:**");
252
+ lines.push(hi.mitigation_plan);
253
+ lines.push("");
254
+ }
255
+ }
161
256
  function appendPvPlanSection(lines, pv) {
162
257
  if (!pv) {
163
258
  lines.push("## Pharmacovigilance Plan");
@@ -623,6 +718,10 @@ export async function handleHtaDossierPrep(rawParams) {
623
718
  lines.push(``);
624
719
  audit = addAssumption(audit, "UK EQ-5D-5L value set transition flagged (NICE consultation 2026-04-15 to 2026-05-13)");
625
720
  }
721
+ if (params.hta_body === "nice") {
722
+ appendSeverityModifierSection(lines, params.severity_modifier);
723
+ appendHealthInequalitiesSection(lines, params.health_inequalities);
724
+ }
626
725
  appendPvPlanSection(lines, params.pv_classification);
627
726
  lines.push(auditToMarkdown(audit));
628
727
  const dossierTextContent = lines.join("\n");
@@ -1 +1 @@
1
- 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1
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@@ -0,0 +1,57 @@
1
+ import type { ToolResult } from "../providers/types.js";
2
+ export declare function handleJcaPicoScope(rawInput: unknown): Promise<ToolResult>;
3
+ export declare const jcaPicoScopeToolSchema: {
4
+ readonly name: "jca.pico_scope";
5
+ readonly description: "Produce the canonical EU Joint Clinical Assessment (JCA) PICO matrix for a drug-indication pair. Returns a consolidated PICO list (per JCA process under Reg. 2021/2282) plus country-specific comparator universes, outcome instrument preferences, population subgroup focus, and a heterogeneity warning when ≥3 distinct comparators emerge across jurisdictions. Pipe `pico_matrix.picos` directly into `hta_dossier({hta_body:\"jca\", picos: ...})`. v1 covers DE/FR/IT/ES/NL + UK (post-Brexit context).";
6
+ readonly annotations: {
7
+ readonly title: "JCA PICO Scope Analyzer";
8
+ readonly readOnlyHint: true;
9
+ readonly destructiveHint: false;
10
+ readonly idempotentHint: true;
11
+ readonly openWorldHint: false;
12
+ };
13
+ readonly inputSchema: {
14
+ readonly type: "object";
15
+ readonly properties: {
16
+ readonly drug: {
17
+ readonly type: "string";
18
+ readonly description: "Drug name.";
19
+ };
20
+ readonly indication: {
21
+ readonly type: "string";
22
+ readonly description: "Disease/condition.";
23
+ };
24
+ readonly drug_class: {
25
+ readonly type: "string";
26
+ readonly enum: readonly ["monoclonal_antibody", "small_molecule", "atmp_cell", "atmp_gene", "atmp_tissue", "biosimilar", "vaccine", "radiopharmaceutical", "other"];
27
+ };
28
+ readonly mechanism_of_action: {
29
+ readonly type: "string";
30
+ };
31
+ readonly line_of_therapy: {
32
+ readonly type: "string";
33
+ readonly enum: readonly ["first_line", "second_line", "third_line_plus", "any"];
34
+ readonly default: "any";
35
+ };
36
+ readonly biomarker_status: {
37
+ readonly type: "string";
38
+ readonly description: "Optional biomarker status (e.g., 'EGFR T790M positive', 'PD-L1 TPS ≥50%').";
39
+ };
40
+ readonly jurisdictions: {
41
+ readonly type: "array";
42
+ readonly items: {
43
+ readonly type: "string";
44
+ readonly enum: readonly ["de", "fr", "it", "es", "nl", "uk", "eu_other"];
45
+ };
46
+ readonly default: readonly ["de", "fr", "it", "es", "nl"];
47
+ };
48
+ readonly regulatory_context: {
49
+ readonly type: "string";
50
+ readonly enum: readonly ["pre_authorisation", "post_authorisation", "conditional_approval"];
51
+ readonly default: "post_authorisation";
52
+ };
53
+ };
54
+ readonly required: readonly ["drug", "indication", "drug_class"];
55
+ };
56
+ };
57
+ //# sourceMappingURL=jcaPicoScope.d.ts.map
@@ -0,0 +1 @@
1
+ {"version":3,"file":"jcaPicoScope.d.ts","sourceRoot":"","sources":["../../src/tools/jcaPicoScope.ts"],"names":[],"mappings":"AAoBA,OAAO,KAAK,EAAE,UAAU,EAAE,MAAM,uBAAuB,CAAC;AAgDxD,wBAAsB,kBAAkB,CACtC,QAAQ,EAAE,OAAO,GAChB,OAAO,CAAC,UAAU,CAAC,CA8LrB;AAED,eAAO,MAAM,sBAAsB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAqCzB,CAAC"}
@@ -0,0 +1,209 @@
1
+ /**
2
+ * jca_pico_scope — EU Joint Clinical Assessment PICO matrix analyzer.
3
+ * Single-call tool that produces the canonical JCA consolidated-PICO list
4
+ * for a drug-indication pair across selected EU jurisdictions. Designed
5
+ * to feed directly into hta_dossier({hta_body:"jca", picos: ...}).
6
+ *
7
+ * See design log #13.
8
+ */
9
+ import { z } from "zod";
10
+ import { addAssumption, addWarning, createAuditRecord, setMethodology, } from "../audit/builder.js";
11
+ import { auditToMarkdown } from "../formatters/markdown.js";
12
+ import { suggestForEnum } from "../util/didYouMean.js";
13
+ import { buildScope } from "../jca/scopeBuilder.js";
14
+ import { JCA_REVISION } from "../jca/countryRegistry.js";
15
+ const DRUG_CLASSES = [
16
+ "monoclonal_antibody",
17
+ "small_molecule",
18
+ "atmp_cell",
19
+ "atmp_gene",
20
+ "atmp_tissue",
21
+ "biosimilar",
22
+ "vaccine",
23
+ "radiopharmaceutical",
24
+ "other",
25
+ ];
26
+ const LINES = ["first_line", "second_line", "third_line_plus", "any"];
27
+ const JURISDICTIONS = [
28
+ "de",
29
+ "fr",
30
+ "it",
31
+ "es",
32
+ "nl",
33
+ "uk",
34
+ "eu_other",
35
+ ];
36
+ const REG_CONTEXTS = [
37
+ "pre_authorisation",
38
+ "post_authorisation",
39
+ "conditional_approval",
40
+ ];
41
+ const JcaPicoScopeSchema = z
42
+ .object({
43
+ drug: z.string().min(1, "drug is required"),
44
+ indication: z.string().min(1, "indication is required"),
45
+ drug_class: z.enum(DRUG_CLASSES),
46
+ mechanism_of_action: z.string().optional(),
47
+ line_of_therapy: z.enum(LINES).default("any"),
48
+ biomarker_status: z.string().optional(),
49
+ jurisdictions: z
50
+ .array(z.enum(JURISDICTIONS))
51
+ .min(1)
52
+ .default(["de", "fr", "it", "es", "nl"]),
53
+ regulatory_context: z.enum(REG_CONTEXTS).default("post_authorisation"),
54
+ })
55
+ .strict();
56
+ export async function handleJcaPicoScope(rawInput) {
57
+ const parsed = JcaPicoScopeSchema.safeParse(rawInput);
58
+ if (!parsed.success) {
59
+ const messages = [];
60
+ for (const issue of parsed.error.issues) {
61
+ if (issue.code === "invalid_enum_value" &&
62
+ typeof issue.received === "string") {
63
+ const suggestions = suggestForEnum(issue.received, issue.options);
64
+ messages.push(`Invalid ${issue.path.join(".")}: "${issue.received}". Allowed: ${issue.options.join(", ")}.${suggestions.length
65
+ ? ` Did you mean ${suggestions.map((s) => `"${s}"`).join(", ")}?`
66
+ : ""}`);
67
+ }
68
+ else {
69
+ messages.push(`${issue.path.join(".") || "input"}: ${issue.message}`);
70
+ }
71
+ }
72
+ throw new Error(messages.join("\n"));
73
+ }
74
+ const input = parsed.data;
75
+ let audit = createAuditRecord("jca.pico_scope", input, "text");
76
+ audit = setMethodology(audit, "EU Regulation 2021/2282 (HTA Regulation) — Joint Clinical Assessment; EUnetHTA Coordination Group methodological guidance; Annex II patient-relevant outcomes hierarchy. National HTA preferences sourced from G-BA/IQWiG, HAS, AIFA, AEMPS/RedETS, Zorginstituut, NICE.");
77
+ const matrix = buildScope({
78
+ drug: input.drug,
79
+ indication: input.indication,
80
+ drug_class: input.drug_class,
81
+ mechanism_of_action: input.mechanism_of_action,
82
+ line_of_therapy: input.line_of_therapy,
83
+ biomarker_status: input.biomarker_status,
84
+ jurisdictions: input.jurisdictions,
85
+ regulatory_context: input.regulatory_context,
86
+ });
87
+ audit = addAssumption(audit, `JCA scope produced for ${input.jurisdictions.join(", ")} (revision ${JCA_REVISION}). ${matrix.picos.length} consolidated PICO(s).`);
88
+ if (matrix.heterogeneity_warning) {
89
+ audit = addWarning(audit, `Comparator heterogeneity: ${matrix.distinct_comparator_count} distinct comparators across jurisdictions. NMA / Bucher feasibility may be compromised.`);
90
+ }
91
+ if (input.regulatory_context === "pre_authorisation") {
92
+ audit = addWarning(audit, "Pre-authorisation context — output is anticipatory only, not a JCA-finalised PICO list.");
93
+ }
94
+ const lines = [];
95
+ lines.push(`# JCA PICO Scope — ${input.drug} (${input.indication})`);
96
+ lines.push("");
97
+ lines.push(`**JCA revision:** ${JCA_REVISION} · **Jurisdictions:** ${input.jurisdictions.join(", ").toUpperCase()} · **Regulatory context:** ${input.regulatory_context}`);
98
+ lines.push("");
99
+ if (input.regulatory_context === "pre_authorisation") {
100
+ lines.push("> ⚠️ **Anticipatory scope only.** JCA scope is finalised at marketing authorisation. Use this output for protocol-design and pre-MA market-access strategy — not for actual JCA submission.");
101
+ lines.push("");
102
+ }
103
+ if (matrix.heterogeneity_warning) {
104
+ lines.push(`> ⚠️ **Comparator heterogeneity warning.** ${matrix.distinct_comparator_count} distinct comparator molecules across ${input.jurisdictions.length} jurisdictions. Run \`evidence_network\` + \`itc_feasibility\` before any quantitative estimation.`);
105
+ lines.push("");
106
+ }
107
+ lines.push("## Rationale");
108
+ lines.push(matrix.rationale);
109
+ lines.push("");
110
+ lines.push(`## Consolidated PICO list (${matrix.picos.length} PICOs)`);
111
+ lines.push("| ID | Population | Comparator | Outcomes |");
112
+ lines.push("|----|------------|------------|----------|");
113
+ for (const p of matrix.picos) {
114
+ lines.push(`| ${p.id} | ${p.population} | ${p.comparator} | ${p.outcomes.join(", ")} |`);
115
+ }
116
+ lines.push("");
117
+ lines.push("*Pipe `pico_matrix.picos` directly into `hta_dossier({hta_body:\"jca\", picos: ...})` to expand into a multi-PICO dossier.*");
118
+ lines.push("");
119
+ for (const c of matrix.country_specific) {
120
+ const flag = { de: "🇩🇪 Germany", fr: "🇫🇷 France", it: "🇮🇹 Italy", es: "🇪🇸 Spain", nl: "🇳🇱 Netherlands", uk: "🇬🇧 United Kingdom", eu_other: "🇪🇺 Other EU member states" }[c.jurisdiction] ?? c.jurisdiction;
121
+ lines.push(`## ${flag} — ${c.hta_body}`);
122
+ if (c.jurisdiction === "uk") {
123
+ lines.push("*Post-Brexit, NICE alignment context only — UK is outside the JCA process but most submissions still target NICE in parallel.*");
124
+ }
125
+ if (c.jurisdiction === "eu_other") {
126
+ lines.push("*v1 of `jca_pico_scope` covers DE/FR/IT/ES/NL + UK only — consult national HTA bodies for jurisdiction-specific comparator preferences.*");
127
+ }
128
+ lines.push("");
129
+ lines.push("**Comparators:**");
130
+ for (const cmp of c.comparators) {
131
+ lines.push(`- **${cmp.molecule}** — ${cmp.rationale}`);
132
+ lines.push(` Outcome instruments: ${cmp.outcome_instrument_preferences.join(", ")}`);
133
+ }
134
+ if (c.population_subgroups.length > 0) {
135
+ lines.push("");
136
+ lines.push("**Population subgroups of HTA interest:**");
137
+ for (const s of c.population_subgroups)
138
+ lines.push(`- ${s}`);
139
+ }
140
+ lines.push("");
141
+ lines.push(`**Outcome priority order:** ${c.outcome_priorities.join(" → ")}`);
142
+ lines.push("");
143
+ }
144
+ // Surrogate-endpoint note for oncology indications
145
+ const isOncology = matrix.country_specific.some((c) => c.outcome_priorities[0] === "OS");
146
+ if (isOncology) {
147
+ lines.push("## Surrogate Endpoints");
148
+ lines.push("JCA prefers patient-relevant outcomes per Annex II of Implementing Regulation 2024/1381. **Surrogate endpoints (PFS, ORR, biomarker response) are accepted as secondary outcomes only and may face JCA scrutiny.** Plan an OS analysis even when PFS is the trial primary endpoint, and pre-specify any OS-from-PFS surrogacy assumptions in the dossier.");
149
+ lines.push("");
150
+ }
151
+ lines.push("## Suggested Next Steps");
152
+ lines.push(`1. Pipe \`pico_matrix.picos\` into \`hta_dossier({hta_body:"jca", submission_type:"initial", drug_name:"${input.drug}", indication:"${input.indication}", picos: ...})\`.`);
153
+ lines.push("2. Run `evidence_network` on the comparator universe to assess connectedness.");
154
+ lines.push("3. Run `itc_feasibility` to determine whether anchored/unanchored ITC, MAIC, or full NMA is appropriate.");
155
+ if (matrix.heterogeneity_warning) {
156
+ lines.push("4. Given the heterogeneity warning, expect multiple PICOs to require separate ITCs rather than a single network analysis.");
157
+ }
158
+ lines.push("");
159
+ lines.push("## References");
160
+ lines.push("- EU Regulation 2021/2282 — HTA Regulation");
161
+ lines.push("- EU Implementing Regulation 2024/1381 — JCA procedural rules");
162
+ lines.push("- EUnetHTA Coordination Group — Methodological Guidance Series");
163
+ lines.push("- Annex II — patient-relevant outcomes hierarchy (mortality, morbidity, HRQoL, AEs)");
164
+ lines.push("- National HTA bodies: G-BA / IQWiG, HAS, AIFA, AEMPS / RedETS, Zorginstituut Nederland, NICE");
165
+ lines.push("");
166
+ lines.push(auditToMarkdown(audit));
167
+ return {
168
+ content: lines.join("\n"),
169
+ audit,
170
+ pico_matrix: matrix,
171
+ };
172
+ }
173
+ export const jcaPicoScopeToolSchema = {
174
+ name: "jca.pico_scope",
175
+ description: "Produce the canonical EU Joint Clinical Assessment (JCA) PICO matrix for a drug-indication pair. Returns a consolidated PICO list (per JCA process under Reg. 2021/2282) plus country-specific comparator universes, outcome instrument preferences, population subgroup focus, and a heterogeneity warning when ≥3 distinct comparators emerge across jurisdictions. Pipe `pico_matrix.picos` directly into `hta_dossier({hta_body:\"jca\", picos: ...})`. v1 covers DE/FR/IT/ES/NL + UK (post-Brexit context).",
176
+ annotations: {
177
+ title: "JCA PICO Scope Analyzer",
178
+ readOnlyHint: true,
179
+ destructiveHint: false,
180
+ idempotentHint: true,
181
+ openWorldHint: false,
182
+ },
183
+ inputSchema: {
184
+ type: "object",
185
+ properties: {
186
+ drug: { type: "string", description: "Drug name." },
187
+ indication: { type: "string", description: "Disease/condition." },
188
+ drug_class: { type: "string", enum: DRUG_CLASSES },
189
+ mechanism_of_action: { type: "string" },
190
+ line_of_therapy: { type: "string", enum: LINES, default: "any" },
191
+ biomarker_status: {
192
+ type: "string",
193
+ description: "Optional biomarker status (e.g., 'EGFR T790M positive', 'PD-L1 TPS ≥50%').",
194
+ },
195
+ jurisdictions: {
196
+ type: "array",
197
+ items: { type: "string", enum: JURISDICTIONS },
198
+ default: ["de", "fr", "it", "es", "nl"],
199
+ },
200
+ regulatory_context: {
201
+ type: "string",
202
+ enum: REG_CONTEXTS,
203
+ default: "post_authorisation",
204
+ },
205
+ },
206
+ required: ["drug", "indication", "drug_class"],
207
+ },
208
+ };
209
+ //# sourceMappingURL=jcaPicoScope.js.map
@@ -0,0 +1 @@
1
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package/package.json CHANGED
@@ -1,13 +1,13 @@
1
1
  {
2
2
  "name": "heor-agent-mcp",
3
- "version": "1.1.0",
3
+ "version": "1.2.0",
4
4
  "mcpName": "io.github.neptun2000/heor-agent",
5
5
  "license": "MIT",
6
6
  "author": "mnaumov",
7
7
  "engines": {
8
8
  "node": ">=20.0.0"
9
9
  },
10
- "description": "AI-powered Health Economics and Outcomes Research (HEOR) MCP server — 20 tools across literature search (44 data sources incl. PubMed/ClinicalTrials.gov/Cochrane/NICE/CADTH/ICER), risk of bias (RoB 2/ROBINS-I/AMSTAR-2), cost-effectiveness modeling (Markov/PartSA/PSA/EVPPI), budget impact analysis, abstract screening, survival curve fitting (NICE DSU TSD 14), indirect comparisons (Bucher/NMA/MAIC/STC), pharmacovigilance study classification (EMA GVP rev 4), MAIC pipeline orchestration, and HTA dossier prep (NICE/EMA/FDA/IQWiG/HAS/EU JCA) with auto-GRADE + PV plan section",
10
+ "description": "AI-powered Health Economics and Outcomes Research (HEOR) MCP server — 21 tools across literature search (44 data sources incl. PubMed/ClinicalTrials.gov/Cochrane/NICE/CADTH/ICER), risk of bias (RoB 2/ROBINS-I/AMSTAR-2), cost-effectiveness modeling (Markov/PartSA/PSA/EVPPI), budget impact analysis, abstract screening, survival curve fitting (NICE DSU TSD 14), indirect comparisons (Bucher/NMA/MAIC/STC), pharmacovigilance study classification (EMA GVP rev 4), EU JCA PICO matrix analyzer, MAIC pipeline orchestration, and HTA dossier prep (NICE/EMA/FDA/IQWiG/HAS/EU JCA) with auto-GRADE + PV plan + NICE severity/inequalities sections",
11
11
  "type": "module",
12
12
  "main": "dist/server.js",
13
13
  "bin": {