heor-agent-mcp 0.1.0

package/dist/tools/costEffectivenessModel.js

@@ -0,0 +1,404 @@
+import { z } from "zod";
+const CEModelSchema = z.object({
+    intervention: z.string().min(1),
+    comparator: z.string().min(1),
+    indication: z.string().min(1),
+    time_horizon: z.union([
+        z.enum(["lifetime", "5yr", "10yr"]),
+        z.number().positive(),
+    ]),
+    perspective: z.enum(["nhs", "us_payer", "societal"]),
+    model_type: z.enum(["markov", "partsa", "decision_tree"]).optional(),
+    clinical_inputs: z.object({
+        efficacy_delta: z.number().min(0).max(1),
+        mortality_reduction: z.number().min(0).max(1).optional(),
+        ae_rate: z.number().min(0).max(1).optional(),
+    }),
+    cost_inputs: z.object({
+        drug_cost_annual: z.number().nonnegative(),
+        admin_cost: z.number().nonnegative().optional(),
+        ae_cost: z.number().nonnegative().optional(),
+        comparator_cost_annual: z.number().nonnegative(),
+    }),
+    utility_inputs: z
+        .object({
+        qaly_on_treatment: z.number().min(0).max(1),
+        qaly_comparator: z.number().min(0).max(1),
+    })
+        .optional(),
+    run_psa: z.boolean().optional(),
+    psa_iterations: z.number().int().min(1).max(10000).optional(),
+    run_owsa: z.boolean().optional(),
+    output_format: z.enum(["text", "json", "docx"]).optional(),
+    project: z.string().optional(),
+});
+import { runPartSA } from "../models/partsa.js";
+import { runPSA } from "../models/psa.js";
+import { runOWSA, buildDefaultOWSAParameters } from "../models/owsa.js";
+import { runMarkovAndComputeICER, } from "../models/modelUtils.js";
+import { createAuditRecord, addAssumption, setMethodology, } from "../audit/builder.js";
+import { auditToMarkdown } from "../formatters/markdown.js";
+import { contentToDocx } from "../formatters/docx.js";
+import { saveModelRun } from "../knowledge/index.js";
+const WTP_THRESHOLDS = {
+    nhs: { low: 20000, high: 30000, currency: "GBP", symbol: "£" },
+    us_payer: { low: 100000, high: 150000, currency: "USD", symbol: "$" },
+    societal: { low: 50000, high: 100000, currency: "USD", symbol: "$" },
+};
+const DISCOUNT_RATE = 0.035;
+function getTimeHorizonYears(horizon) {
+    if (horizon === "lifetime")
+        return 40;
+    if (horizon === "5yr")
+        return 5;
+    if (horizon === "10yr")
+        return 10;
+    return Number(horizon);
+}
+function wtpVerdict(icer, threshold) {
+    if (!isFinite(icer) && icer < 0)
+        return "dominated";
+    if (!isFinite(icer))
+        return "not_cost_effective";
+    if (icer < threshold.low)
+        return "cost_effective";
+    if (icer < threshold.high)
+        return "borderline";
+    return "not_cost_effective";
+}
+function buildWTPAssessment(icer, perspective) {
+    const threshold = WTP_THRESHOLDS[perspective];
+    return {
+        threshold_low: threshold.low,
+        threshold_high: threshold.high,
+        currency: threshold.currency,
+        symbol: threshold.symbol,
+        verdict: wtpVerdict(icer, threshold),
+    };
+}
+export async function handleCostEffectivenessModel(rawParams) {
+    const params = CEModelSchema.parse(rawParams);
+    const outputFormat = params.output_format ?? "text";
+    let audit = createAuditRecord("cost_effectiveness_model", params, outputFormat);
+    const modelType = params.model_type ?? "markov";
+    const years = getTimeHorizonYears(params.time_horizon);
+    const threshold = WTP_THRESHOLDS[params.perspective];
+    const { symbol } = threshold;
+    audit = setMethodology(audit, `Markov model (multi-state) with half-cycle correction and PSA — ${modelType === "partsa" ? "Partitioned Survival Analysis" : "2-state Markov"}`);
+    audit = addAssumption(audit, `Discount rate: ${DISCOUNT_RATE * 100}% (NICE reference case)`);
+    audit = addAssumption(audit, `Time horizon: ${years} years (${params.time_horizon})`);
+    audit = addAssumption(audit, `Perspective: ${params.perspective}`);
+    audit = addAssumption(audit, `Markov cycle length: 1 year`);
+    if (!params.utility_inputs) {
+        audit = addAssumption(audit, `QALY estimate derived from efficacy delta (utility inputs not provided) — use with caution`);
+    }
+    // --- Base case ---
+    let delta_cost;
+    let delta_qaly;
+    let icer;
+    let intervention_cost;
+    let comparator_cost;
+    let intervention_qaly;
+    let comparator_qaly;
+    let intervention_lys;
+    let comparator_lys;
+    let stateNames;
+    let nCycles;
+    if (modelType === "partsa" && params.survival_inputs) {
+        const si = params.survival_inputs;
+        const partSAResult = runPartSA({
+            intervention_survival: {
+                os_median_months: si.os_median_months ?? 24,
+                pfs_median_months: si.pfs_median_months ?? 12,
+                distribution: si.survival_distribution ?? "exponential",
+                weibull_shape: si.weibull_shape,
+            },
+            comparator_survival: {
+                os_median_months: si.os_median_months_comparator ?? 18,
+                pfs_median_months: si.pfs_median_months_comparator ?? 9,
+                distribution: si.survival_distribution ?? "exponential",
+                weibull_shape: si.weibull_shape,
+            },
+            states: ["PFS", "PD", "Dead"],
+            utility_pfs: params.utility_inputs?.qaly_on_treatment ?? 0.75,
+            utility_pd: params.utility_inputs?.qaly_comparator ?? 0.55,
+            cost_pfs_annual: params.cost_inputs.drug_cost_annual,
+            cost_pd_annual: params.cost_inputs.comparator_cost_annual,
+            n_cycles: years,
+            cycle_length_years: 1,
+            discount_rate_costs: DISCOUNT_RATE,
+            discount_rate_outcomes: DISCOUNT_RATE,
+        });
+        delta_cost =
+            partSAResult.intervention.total_cost - partSAResult.comparator.total_cost;
+        delta_qaly =
+            partSAResult.intervention.total_qaly - partSAResult.comparator.total_qaly;
+        icer =
+            delta_qaly > 0
+                ? delta_cost / delta_qaly
+                : delta_qaly < 0
+                    ? -Infinity
+                    : Infinity;
+        intervention_cost = partSAResult.intervention.total_cost;
+        comparator_cost = partSAResult.comparator.total_cost;
+        intervention_qaly = partSAResult.intervention.total_qaly;
+        comparator_qaly = partSAResult.comparator.total_qaly;
+        intervention_lys = partSAResult.intervention.total_lys;
+        comparator_lys = partSAResult.comparator.total_lys;
+        stateNames = ["PFS", "PD", "Dead"];
+        nCycles = years;
+    }
+    else {
+        // Default: Markov
+        const markovResult = runMarkovAndComputeICER(params);
+        delta_cost = markovResult.delta_cost;
+        delta_qaly = markovResult.delta_qaly;
+        icer = markovResult.icer;
+        intervention_cost = markovResult.intervention_cost;
+        comparator_cost = markovResult.comparator_cost;
+        intervention_qaly = markovResult.intervention_qaly;
+        comparator_qaly = markovResult.comparator_qaly;
+        intervention_lys = markovResult.intervention_lys;
+        comparator_lys = markovResult.comparator_lys;
+        stateNames = params.states ?? ["On-Treatment", "Off-Treatment"];
+        nCycles = years;
+    }
+    const incremental_lys = intervention_lys - comparator_lys;
+    // --- PSA ---
+    let psaSummary;
+    if (params.run_psa !== false && modelType !== "partsa") {
+        const n_iterations = Math.min(10000, Math.max(1, params.psa_iterations ?? 1000));
+        const psaResult = runPSA({
+            base_params: params,
+            n_iterations,
+            seed: 12345,
+        });
+        psaSummary = {
+            iterations: n_iterations,
+            mean_icer: psaResult.mean_icer,
+            ci_icer_lower: psaResult.ci_icer_lower,
+            ci_icer_upper: psaResult.ci_icer_upper,
+            prob_cost_effective: psaResult.prob_cost_effective,
+            ceac: psaResult.ceac,
+            evpi: psaResult.evpi,
+            scatter: psaResult.scatter_sample.map((it) => ({
+                delta_cost: it.delta_cost,
+                delta_qaly: it.delta_qaly,
+            })),
+        };
+    }
+    // --- OWSA ---
+    let owsaResults;
+    if (params.run_owsa !== false) {
+        const owsaParams = buildDefaultOWSAParameters(params);
+        const rawOWSA = runOWSA(params, owsaParams, (p) => runMarkovAndComputeICER(p));
+        owsaResults = rawOWSA.map((r) => ({
+            parameter: r.parameter,
+            low_value: r.low_value,
+            high_value: r.high_value,
+            icer_low: r.icer_low,
+            icer_high: r.icer_high,
+            impact: r.impact,
+        }));
+    }
+    // --- WTP Analysis ---
+    const wtp_analysis = {
+        nhs: buildWTPAssessment(icer, "nhs"),
+        us_payer: buildWTPAssessment(icer, "us_payer"),
+        societal: buildWTPAssessment(icer, "societal"),
+    };
+    // --- Build result ---
+    const modelResult = {
+        base_case: {
+            icer,
+            delta_cost,
+            delta_qaly,
+            incremental_lys,
+            total_cost_intervention: intervention_cost,
+            total_cost_comparator: comparator_cost,
+            total_qaly_intervention: intervention_qaly,
+            total_qaly_comparator: comparator_qaly,
+        },
+        psa: psaSummary,
+        owsa: owsaResults,
+        wtp_analysis,
+        model_metadata: {
+            model_type: modelType,
+            states: stateNames,
+            cycles: nCycles,
+            cycle_length: "1 year",
+            discount_rate_costs: DISCOUNT_RATE,
+            discount_rate_outcomes: DISCOUNT_RATE,
+            time_horizon_years: years,
+        },
+        audit,
+    };
+    if (outputFormat === "json") {
+        return { content: modelResult, audit };
+    }
+    // --- Text output (backwards-compatible) ---
+    const icerFormatted = isFinite(icer)
+        ? Math.round(icer).toLocaleString()
+        : "Dominated";
+    const perspectiveVerdict = wtp_analysis[params.perspective];
+    const interpretation = isFinite(icer) && icer >= 0
+        ? icer < threshold.low
+            ? `${symbol}${icerFormatted}/QALY — likely cost-effective (below NICE threshold of ${symbol}${threshold.low.toLocaleString()})`
+            : icer < threshold.high
+                ? `${symbol}${icerFormatted}/QALY — borderline cost-effective (within ${symbol}${threshold.low.toLocaleString()}–${symbol}${threshold.high.toLocaleString()} threshold range)`
+                : `${symbol}${icerFormatted}/QALY — not cost-effective at standard threshold`
+        : "Dominated — intervention costs more and provides less benefit than comparator";
+    // PSA section
+    const psaSection = [];
+    if (psaSummary) {
+        const pcePerspective = perspectiveVerdict.currency === "GBP"
+            ? (psaSummary.prob_cost_effective["nhs_low"] ?? 0)
+            : (psaSummary.prob_cost_effective["us_payer_low"] ?? 0);
+        const pcePercent = Math.round(pcePerspective * 100);
+        psaSection.push(`### Probabilistic Sensitivity Analysis (PSA)`, `Based on ${psaSummary.iterations.toLocaleString()} Monte Carlo iterations:`, `- **Mean ICER:** ${symbol}${Math.round(psaSummary.mean_icer).toLocaleString()}/QALY`, `- **95% CI:** ${symbol}${Math.round(psaSummary.ci_icer_lower).toLocaleString()} – ${symbol}${Math.round(psaSummary.ci_icer_upper).toLocaleString()}/QALY`, `- **Probability cost-effective** at ${params.perspective} threshold: **${pcePercent}%**`, `- **EVPI:** ${symbol}${Math.round(psaSummary.evpi).toLocaleString()} (expected value of perfect information)`, ``);
+    }
+    // OWSA section (top 5)
+    const owsaSection = [];
+    if (owsaResults && owsaResults.length > 0) {
+        owsaSection.push(`### One-Way Sensitivity Analysis (Tornado)`);
+        owsaSection.push(`Top ${Math.min(5, owsaResults.length)} parameters by ICER impact:`);
+        owsaSection.push(`| Parameter | Low ICER | High ICER | Impact |`);
+        owsaSection.push(`|-----------|----------|-----------|--------|`);
+        for (const r of owsaResults.slice(0, 5)) {
+            const low = isFinite(r.icer_low)
+                ? `${symbol}${Math.round(r.icer_low).toLocaleString()}`
+                : "N/A";
+            const high = isFinite(r.icer_high)
+                ? `${symbol}${Math.round(r.icer_high).toLocaleString()}`
+                : "N/A";
+            const impact = isFinite(r.impact)
+                ? `${symbol}${Math.round(r.impact).toLocaleString()}`
+                : "N/A";
+            owsaSection.push(`| ${r.parameter} | ${low} | ${high} | ${impact} |`);
+        }
+        owsaSection.push(``);
+    }
+    const textLines = [
+        `## Cost-Effectiveness Analysis: ${params.intervention} vs ${params.comparator}`,
+        `**Indication:** ${params.indication} | **Perspective:** ${params.perspective.toUpperCase()} | **Horizon:** ${params.time_horizon}`,
+        ``,
+        `### ICER Result`,
+        `**${symbol}${icerFormatted} per QALY gained**`,
+        ``,
+        `**Interpretation:** ${interpretation}`,
+        ``,
+        `### Base Case Summary`,
+        `| Metric | ${params.intervention} | ${params.comparator} | Incremental |`,
+        `|--------|${"-".repeat(params.intervention.length + 2)}|${"-".repeat(params.comparator.length + 2)}|-------------|`,
+        `| Total Cost | ${symbol}${Math.round(intervention_cost).toLocaleString()} | ${symbol}${Math.round(comparator_cost).toLocaleString()} | ${symbol}${Math.round(delta_cost).toLocaleString()} |`,
+        `| Total QALYs | ${intervention_qaly.toFixed(3)} | ${comparator_qaly.toFixed(3)} | ${delta_qaly.toFixed(3)} |`,
+        `| Life Years | ${intervention_lys.toFixed(2)} | ${comparator_lys.toFixed(2)} | ${incremental_lys.toFixed(2)} |`,
+        ``,
+        ...psaSection,
+        ...owsaSection,
+        `### Model Structure`,
+        `Multi-state Markov model with half-cycle correction. Discounted at ${DISCOUNT_RATE * 100}% per NICE reference case.`,
+        `States: ${stateNames.join(", ")} | Cycles: ${nCycles} annual cycles`,
+        ``,
+        `---`,
+        `> ⚠️ **Disclaimer:** This is a preliminary model for orientation purposes only. Results require validation by a qualified health economist before use in any HTA submission or payer negotiation.`,
+        ``,
+        auditToMarkdown(audit),
+    ].join("\n");
+    if (params.project) {
+        try {
+            const metadata = {
+                intervention: params.intervention,
+                comparator: params.comparator,
+                indication: params.indication,
+                perspective: params.perspective,
+                model_type: params.model_type ?? "markov",
+            };
+            await saveModelRun(params.project, metadata, textLines);
+        }
+        catch {
+            // fail silently — don't break the tool
+        }
+    }
+    if (outputFormat === "docx") {
+        const base64 = await contentToDocx("Cost-Effectiveness Analysis Report", textLines, audit);
+        const content = `[DOCX Report Generated]\n\nBase64-encoded DOCX (${Math.round(base64.length / 1024)}KB):\n${base64}`;
+        return { content, audit };
+    }
+    const content = textLines;
+    return { content, audit };
+}
+export const costEffectivenessModelToolSchema = {
+    name: "cost_effectiveness_model",
+    description: "Build a cost-utility analysis (ICER, QALY, PSA, sensitivity analysis) for a drug vs comparator. Follows ISPOR good practice guidelines and NICE reference case. Includes probabilistic sensitivity analysis (PSA), one-way sensitivity, and cost-effectiveness acceptability curve (CEAC).",
+    inputSchema: {
+        type: "object",
+        properties: {
+            intervention: { type: "string", description: "Drug or treatment name" },
+            comparator: {
+                type: "string",
+                description: "Comparator (standard of care)",
+            },
+            indication: { type: "string", description: "Disease or condition" },
+            time_horizon: {
+                type: "string",
+                description: "Modelling horizon: 'lifetime', '5yr', '10yr', or years as number",
+            },
+            perspective: { type: "string", enum: ["nhs", "us_payer", "societal"] },
+            model_type: {
+                type: "string",
+                enum: ["markov", "partsa", "decision_tree"],
+                description: "Model type. Default: markov. Use 'partsa' for oncology.",
+            },
+            clinical_inputs: {
+                type: "object",
+                properties: {
+                    efficacy_delta: { type: "number" },
+                    mortality_reduction: { type: "number" },
+                    ae_rate: { type: "number" },
+                },
+                required: ["efficacy_delta"],
+            },
+            cost_inputs: {
+                type: "object",
+                properties: {
+                    drug_cost_annual: { type: "number" },
+                    admin_cost: { type: "number" },
+                    ae_cost: { type: "number" },
+                    comparator_cost_annual: { type: "number" },
+                },
+                required: ["drug_cost_annual", "comparator_cost_annual"],
+            },
+            utility_inputs: {
+                type: "object",
+                properties: {
+                    qaly_on_treatment: { type: "number" },
+                    qaly_comparator: { type: "number" },
+                },
+            },
+            run_psa: {
+                type: "boolean",
+                description: "Run probabilistic sensitivity analysis (default: true)",
+            },
+            psa_iterations: {
+                type: "number",
+                description: "PSA iterations (default: 1000, max: 10000)",
+            },
+            output_format: { type: "string", enum: ["text", "json", "docx"] },
+            project: {
+                type: "string",
+                description: "Project ID for knowledge base persistence. When set, model run is saved to ~/.heor-agent/projects/{project}/raw/models/",
+            },
+        },
+        required: [
+            "intervention",
+            "comparator",
+            "indication",
+            "time_horizon",
+            "perspective",
+            "clinical_inputs",
+            "cost_inputs",
+        ],
+    },
+};
+//# sourceMappingURL=costEffectivenessModel.js.map

package/dist/tools/costEffectivenessModel.js.map

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package/dist/tools/htaDossierPrep.d.ts

@@ -0,0 +1,69 @@
+import type { ToolResult } from "../providers/types.js";
+export declare function handleHtaDossierPrep(rawParams: unknown): Promise<ToolResult>;
+export declare const htaDossierPrepToolSchema: {
+    name: string;
+    description: string;
+    inputSchema: {
+        type: string;
+        properties: {
+            hta_body: {
+                type: string;
+                enum: string[];
+                description: string;
+            };
+            submission_type: {
+                type: string;
+                enum: string[];
+                description: string;
+            };
+            drug_name: {
+                type: string;
+            };
+            indication: {
+                type: string;
+            };
+            evidence_summary: {
+                description: string;
+            };
+            model_results: {
+                description: string;
+            };
+            picos: {
+                type: string;
+                description: string;
+                items: {
+                    type: string;
+                    properties: {
+                        id: {
+                            type: string;
+                            description: string;
+                        };
+                        population: {
+                            type: string;
+                        };
+                        comparator: {
+                            type: string;
+                        };
+                        outcomes: {
+                            type: string;
+                            items: {
+                                type: string;
+                            };
+                        };
+                    };
+                    required: string[];
+                };
+            };
+            output_format: {
+                type: string;
+                enum: string[];
+            };
+            project: {
+                type: string;
+                description: string;
+            };
+        };
+        required: string[];
+    };
+};
+//# sourceMappingURL=htaDossierPrep.d.ts.map

package/dist/tools/htaDossierPrep.d.ts.map

@@ -0,0 +1 @@
+{"version":3,"file":"htaDossierPrep.d.ts","sourceRoot":"","sources":["../../src/tools/htaDossierPrep.ts"],"names":[],"mappings":"AACA,OAAO,KAAK,EAEV,UAAU,EAGX,MAAM,uBAAuB,CAAC;AA0Y/B,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CA4FrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAsDpC,CAAC"}