heor-agent-mcp 0.2.0 → 0.7.0

package/dist/tools/costEffectivenessModel.js.map

@@ -1 +1 @@
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package/dist/tools/htaDossierPrep.d.ts.map

@@ -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;AA8Y/B,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CA+FrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAsDpC,CAAC"}
+{"version":3,"file":"htaDossierPrep.d.ts","sourceRoot":"","sources":["../../src/tools/htaDossierPrep.ts"],"names":[],"mappings":"AACA,OAAO,KAAK,EAEV,UAAU,EAGX,MAAM,uBAAuB,CAAC;AAwiB/B,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CAiHrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CAsDpC,CAAC"}

package/dist/tools/htaDossierPrep.js

@@ -81,6 +81,116 @@ const METHODOLOGY_BY_BODY = {
     has: "HAS transparency committee dossier format",
     jca: "EUHTA Regulation (EU) 2021/2282 — Joint Clinical Assessment",
 };
+/**
+ * Auto-generate GRADE evidence quality assessment from literature results.
+ *
+ * GRADE domains: Risk of bias, Inconsistency, Indirectness, Imprecision, Publication bias
+ * Ratings: High, Moderate, Low, Very Low
+ *
+ * Uses study type counts and basic heuristics from the evidence set.
+ */
+function generateGradeTable(evidence, outcomes) {
+    if (evidence.length === 0)
+        return "";
+    // Count study types
+    const rctCount = evidence.filter((r) => r.study_type?.toLowerCase().includes("rct") ||
+        r.study_type?.toLowerCase().includes("randomized") ||
+        r.study_type?.toLowerCase().includes("randomised")).length;
+    const maCount = evidence.filter((r) => r.study_type?.toLowerCase().includes("meta") ||
+        r.study_type?.toLowerCase().includes("systematic")).length;
+    const obsCount = evidence.filter((r) => r.study_type?.toLowerCase().includes("observational") ||
+        r.study_type?.toLowerCase().includes("cohort") ||
+        r.study_type?.toLowerCase().includes("case")).length;
+    // Base certainty: RCTs start High, observational starts Low
+    const hasRCTs = rctCount > 0;
+    const hasMAs = maCount > 0;
+    function assessOutcome(outcome) {
+        // Check if any evidence mentions this outcome
+        const relevant = evidence.filter((r) => r.title?.toLowerCase().includes(outcome.toLowerCase()) ||
+            r.abstract?.toLowerCase().includes(outcome.toLowerCase()));
+        const nRelevant = relevant.length;
+        // Risk of bias
+        const rob = hasRCTs || hasMAs ? "Low" : "High";
+        // Inconsistency: if multiple studies, assume some inconsistency possible
+        const inconsistency = nRelevant > 3 ? "Low" : nRelevant > 1 ? "Moderate" : "Serious";
+        // Indirectness: assume moderate unless direct evidence exists
+        const indirectness = nRelevant > 0 ? "Low" : "Serious";
+        // Imprecision: based on study count
+        const imprecision = nRelevant >= 3 ? "Low" : nRelevant >= 1 ? "Moderate" : "Serious";
+        // Publication bias
+        const pub_bias = hasMAs ? "Low" : nRelevant >= 5 ? "Low" : "Suspected";
+        // Overall certainty
+        let downgrades = 0;
+        if (rob === "High")
+            downgrades++;
+        if (inconsistency === "Serious")
+            downgrades++;
+        if (indirectness === "Serious")
+            downgrades++;
+        if (imprecision === "Serious")
+            downgrades++;
+        if (pub_bias === "Suspected")
+            downgrades++;
+        const baseLevel = hasRCTs ? 4 : 2; // High=4, Low=2
+        const finalLevel = Math.max(1, baseLevel - downgrades);
+        const certainty = finalLevel >= 4
+            ? "High"
+            : finalLevel >= 3
+                ? "Moderate"
+                : finalLevel >= 2
+                    ? "Low"
+                    : "Very Low";
+        const rationale = [
+            rob !== "Low" ? `RoB: ${rob}` : "",
+            inconsistency !== "Low" ? `Inconsistency: ${inconsistency}` : "",
+            indirectness !== "Low" ? `Indirectness: ${indirectness}` : "",
+            imprecision !== "Low" ? `Imprecision: ${imprecision}` : "",
+            pub_bias !== "Low" ? `Pub. bias: ${pub_bias}` : "",
+        ]
+            .filter(Boolean)
+            .join("; ");
+        return {
+            certainty,
+            rob,
+            inconsistency,
+            indirectness,
+            imprecision,
+            pub_bias,
+            rationale: rationale || "No downgrading",
+        };
+    }
+    const assessedOutcomes = outcomes.length > 0
+        ? outcomes
+        : [
+            "overall survival",
+            "progression-free survival",
+            "quality of life",
+            "adverse events",
+        ];
+    const lines = [
+        `### GRADE Evidence Quality Assessment`,
+        ``,
+        `Based on ${evidence.length} studies (${rctCount} RCTs, ${maCount} systematic reviews/meta-analyses, ${obsCount} observational):`,
+        ``,
+        `| Outcome | Certainty | RoB | Inconsistency | Indirectness | Imprecision | Pub. Bias | Rationale |`,
+        `|---------|-----------|-----|---------------|-------------|-------------|-----------|-----------|`,
+    ];
+    for (const outcome of assessedOutcomes) {
+        const a = assessOutcome(outcome);
+        const certIcon = a.certainty === "High"
+            ? "++++"
+            : a.certainty === "Moderate"
+                ? "+++-"
+                : a.certainty === "Low"
+                    ? "++--"
+                    : "+---";
+        lines.push(`| ${outcome} | **${a.certainty}** ${certIcon} | ${a.rob} | ${a.inconsistency} | ${a.indirectness} | ${a.imprecision} | ${a.pub_bias} | ${a.rationale} |`);
+    }
+    lines.push(``);
+    lines.push(`> **Note:** This is an automated GRADE assessment based on study counts and types. A definitive GRADE evaluation requires clinical expert judgment on each domain. See [GRADE Handbook](https://gdt.gradepro.org/app/handbook/handbook.html).`);
+    lines.push(``);
+    return lines.join("\n");
+}
 function buildSection(name, drugName, indication, evidenceSummary) {
     const evidence = typeof evidenceSummary === "string"
         ? evidenceSummary
@@ -326,6 +436,15 @@ export async function handleHtaDossierPrep(rawParams) {
             audit = addWarning(audit, `Section "${sectionName}" requires additional input`);
         }
     }
+    // Auto-generate GRADE table when evidence is provided as LiteratureResult[]
+    if (Array.isArray(params.evidence_summary) &&
+        params.evidence_summary.length > 0) {
+        const gradeTable = generateGradeTable(params.evidence_summary, []);
+        if (gradeTable) {
+            lines.push(gradeTable);
+            audit = addAssumption(audit, "GRADE evidence quality assessment auto-generated from literature search results");
+        }
+    }
     if (gaps.length > 0) {
         lines.push(`---`);
         lines.push(`## Gap Analysis`);

package/dist/tools/htaDossierPrep.js.map

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package/dist/tools/indirectComparison.d.ts

@@ -0,0 +1,73 @@
+import type { ToolResult } from "../providers/types.js";
+export declare function handleIndirectComparison(rawParams: unknown): Promise<ToolResult>;
+export declare const indirectComparisonToolSchema: {
+    name: string;
+    description: string;
+    inputSchema: {
+        type: string;
+        properties: {
+            comparisons: {
+                type: string;
+                items: {
+                    type: string;
+                    properties: {
+                        intervention: {
+                            type: string;
+                            description: string;
+                        };
+                        comparator: {
+                            type: string;
+                            description: string;
+                        };
+                        outcome: {
+                            type: string;
+                            description: string;
+                        };
+                        measure: {
+                            type: string;
+                            enum: string[];
+                            description: string;
+                        };
+                        estimate: {
+                            type: string;
+                            description: string;
+                        };
+                        ci_lower: {
+                            type: string;
+                            description: string;
+                        };
+                        ci_upper: {
+                            type: string;
+                            description: string;
+                        };
+                        source: {
+                            type: string;
+                            description: string;
+                        };
+                    };
+                    required: string[];
+                };
+                description: string;
+            };
+            target: {
+                type: string;
+                properties: {
+                    intervention: {
+                        type: string;
+                    };
+                    comparator: {
+                        type: string;
+                    };
+                };
+                description: string;
+            };
+            method: {
+                type: string;
+                enum: string[];
+                description: string;
+            };
+        };
+        required: string[];
+    };
+};
+//# sourceMappingURL=indirectComparison.d.ts.map

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

@@ -0,0 +1 @@
+{"version":3,"file":"indirectComparison.d.ts","sourceRoot":"","sources":["../../src/tools/indirectComparison.ts"],"names":[],"mappings":"AACA,OAAO,KAAK,EAAE,UAAU,EAAE,MAAM,uBAAuB,CAAC;AA2DxD,wBAAsB,wBAAwB,CAC5C,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CAmHrB;AAED,eAAO,MAAM,4BAA4B;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;CA+ExC,CAAC"}

package/dist/tools/indirectComparison.js

@@ -0,0 +1,191 @@
+import { z } from "zod";
+import { findIndirectPaths } from "../network/pathfinder.js";
+import { computeIndirectComparison } from "../network/bucher.js";
+import { frequentistNMA } from "../network/frequentistNma.js";
+import { comparisonToMarkdown } from "../formatters/comparisonMarkdown.js";
+import { createAuditRecord, setMethodology } from "../audit/builder.js";
+const DirectComparisonSchema = z.object({
+    intervention: z.string().describe("Treatment name (e.g., 'Semaglutide')"),
+    comparator: z.string().describe("Comparator name (e.g., 'Placebo')"),
+    outcome: z.string().describe("Outcome measured (e.g., 'HbA1c change')"),
+    measure: z
+        .enum(["MD", "OR", "RR", "HR"])
+        .describe("Effect measure: MD (mean difference), OR (odds ratio), RR (risk ratio), HR (hazard ratio)"),
+    estimate: z.number().describe("Point estimate"),
+    ci_lower: z.number().describe("Lower bound of 95% CI"),
+    ci_upper: z.number().describe("Upper bound of 95% CI"),
+    source: z.string().describe("Trial or study name (e.g., 'SUSTAIN-1')"),
+});
+const IndirectComparisonSchema = z.object({
+    comparisons: z
+        .array(DirectComparisonSchema)
+        .min(2)
+        .max(100)
+        .describe("Array of direct comparisons with effect sizes. Need at least 2 comparisons sharing a common comparator."),
+    target: z
+        .object({
+        intervention: z.string(),
+        comparator: z.string(),
+    })
+        .optional()
+        .describe("Specific comparison to compute. If omitted, all possible indirect comparisons are computed."),
+    method: z
+        .enum(["auto", "bucher", "frequentist_nma"])
+        .optional()
+        .describe("Method: 'auto' (default) selects based on network structure, 'bucher' for simple A-B-C paths, 'frequentist_nma' for full network analysis."),
+});
+const LIMITATIONS = [
+    "Transitivity assumption: populations across trials must be similar enough for the common comparator to act as a valid bridge",
+    "Fixed-effect model: does not account for between-study heterogeneity beyond sampling error",
+    "Indirect comparisons are always less precise (wider CIs) than direct head-to-head evidence",
+    "No inconsistency testing: when both direct and indirect evidence exist, this tool does not test whether they agree",
+    "User-supplied data: accuracy depends on correctly entered effect sizes and confidence intervals",
+];
+export async function handleIndirectComparison(rawParams) {
+    const params = IndirectComparisonSchema.parse(rawParams);
+    const comparisons = params.comparisons;
+    const methodPref = params.method ?? "auto";
+    let audit = createAuditRecord("indirect_comparison", {
+        n_comparisons: comparisons.length,
+        method: methodPref,
+        target: params.target,
+    }, "text");
+    audit = setMethodology(audit, "Indirect treatment comparison (Bucher method / Frequentist NMA)");
+    // Determine method
+    const treatments = new Set();
+    for (const c of comparisons) {
+        treatments.add(c.intervention.toLowerCase());
+        treatments.add(c.comparator.toLowerCase());
+    }
+    const nTreatments = treatments.size;
+    // Group by outcome
+    const outcomes = new Set(comparisons.map((c) => c.outcome));
+    const allEstimates = [];
+    const warnings = [];
+    let methodUsed = "bucher";
+    for (const outcome of outcomes) {
+        const outcomeComparisons = comparisons.filter((c) => c.outcome === outcome);
+        const measures = new Set(outcomeComparisons.map((c) => c.measure));
+        for (const measure of measures) {
+            const measureComparisons = outcomeComparisons.filter((c) => c.measure === measure);
+            // Count unique edges for this outcome+measure
+            const edges = new Set(measureComparisons.map((c) => [c.intervention, c.comparator]
+                .map((s) => s.toLowerCase())
+                .sort()
+                .join("↔")));
+            const useNMA = methodPref === "frequentist_nma" ||
+                (methodPref === "auto" && edges.size >= 3 && nTreatments >= 3);
+            if (useNMA) {
+                const nmaEstimates = frequentistNMA(measureComparisons, outcome, measure);
+                allEstimates.push(...nmaEstimates);
+                if (methodUsed === "bucher" && allEstimates.length > 0) {
+                    methodUsed = "frequentist_nma";
+                }
+            }
+            else {
+                // Bucher: find paths and compute
+                const paths = findIndirectPaths(measureComparisons, params.target);
+                if (paths.length === 0 && !params.target) {
+                    warnings.push(`No indirect paths found for outcome "${outcome}" (${measure}). Ensure comparisons share a common comparator.`);
+                }
+                for (const path of paths) {
+                    try {
+                        const est = computeIndirectComparison(path.a, path.c, path.bridge, path.abComparisons, path.bcComparisons, outcome, measure);
+                        allEstimates.push(est);
+                    }
+                    catch (err) {
+                        warnings.push(`Failed to compute ${path.a} vs ${path.c} via ${path.bridge}: ${err instanceof Error ? err.message : String(err)}`);
+                    }
+                }
+            }
+        }
+    }
+    if (methodUsed === "bucher" &&
+        allEstimates.some((e) => e.method === "frequentist_nma")) {
+        methodUsed = "mixed";
+    }
+    const result = {
+        estimates: allEstimates,
+        method: methodUsed,
+        warnings,
+        limitations: LIMITATIONS,
+    };
+    const markdown = comparisonToMarkdown(result);
+    return { content: markdown, audit };
+}
+export const indirectComparisonToolSchema = {
+    name: "indirect_comparison",
+    description: "Compute indirect treatment comparisons using the Bucher method (single common comparator) or frequentist network meta-analysis (full network). Requires user-supplied effect sizes (point estimates + 95% CI) from published trials. Supports mean differences (MD) and ratio measures (OR, RR, HR). Auto-selects method based on network structure, or user can specify.",
+    inputSchema: {
+        type: "object",
+        properties: {
+            comparisons: {
+                type: "array",
+                items: {
+                    type: "object",
+                    properties: {
+                        intervention: {
+                            type: "string",
+                            description: "Treatment name",
+                        },
+                        comparator: {
+                            type: "string",
+                            description: "Comparator name",
+                        },
+                        outcome: {
+                            type: "string",
+                            description: "Outcome (e.g., 'HbA1c change')",
+                        },
+                        measure: {
+                            type: "string",
+                            enum: ["MD", "OR", "RR", "HR"],
+                            description: "MD = mean difference, OR = odds ratio, RR = risk ratio, HR = hazard ratio",
+                        },
+                        estimate: {
+                            type: "number",
+                            description: "Point estimate",
+                        },
+                        ci_lower: {
+                            type: "number",
+                            description: "Lower 95% CI",
+                        },
+                        ci_upper: {
+                            type: "number",
+                            description: "Upper 95% CI",
+                        },
+                        source: {
+                            type: "string",
+                            description: "Trial name (e.g., 'SUSTAIN-1')",
+                        },
+                    },
+                    required: [
+                        "intervention",
+                        "comparator",
+                        "outcome",
+                        "measure",
+                        "estimate",
+                        "ci_lower",
+                        "ci_upper",
+                        "source",
+                    ],
+                },
+                description: "Direct comparisons with effect sizes. Need at least 2 sharing a common comparator. Ask the user for: point estimate, 95% CI, outcome name, and effect measure (MD/OR/RR/HR) from each trial.",
+            },
+            target: {
+                type: "object",
+                properties: {
+                    intervention: { type: "string" },
+                    comparator: { type: "string" },
+                },
+                description: "Specific comparison to compute. Omit to compute all possible.",
+            },
+            method: {
+                type: "string",
+                enum: ["auto", "bucher", "frequentist_nma"],
+                description: "auto (default): Bucher for simple paths, Frequentist NMA for 3+ edges. Or force a specific method.",
+            },
+        },
+        required: ["comparisons"],
+    },
+};
+//# sourceMappingURL=indirectComparison.js.map

package/dist/tools/indirectComparison.js.map

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

@@ -1 +1 @@
-{"version":3,"file":"knowledgeWrite.d.ts","sourceRoot":"","sources":["../../src/tools/knowledgeWrite.ts"],"names":[],"mappings":"AAEA,OAAO,KAAK,EAAE,UAAU,EAAE,MAAM,uBAAuB,CAAC;AASxD,wBAAsB,oBAAoB,CAAC,SAAS,EAAE,OAAO,GAAG,OAAO,CAAC,UAAU,CAAC,CAiBlF;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;CAYpC,CAAC"}
+{"version":3,"file":"knowledgeWrite.d.ts","sourceRoot":"","sources":["../../src/tools/knowledgeWrite.ts"],"names":[],"mappings":"AAEA,OAAO,KAAK,EAAE,UAAU,EAAE,MAAM,uBAAuB,CAAC;AAiBxD,wBAAsB,oBAAoB,CACxC,SAAS,EAAE,OAAO,GACjB,OAAO,CAAC,UAAU,CAAC,CAyBrB;AAED,eAAO,MAAM,wBAAwB;;;;;;;;;;;;;;;;;;;;;CAqBpC,CAAC"}

package/dist/tools/knowledgeWrite.js

@@ -3,7 +3,15 @@ import { writeWikiFile } from "../knowledge/wikiStore.js";
 import { createAuditRecord } from "../audit/builder.js";
 const KnowledgeWriteSchema = z.object({
     project: z.string().min(1),
-    path: z.string().min(1),
+    path: z
+        .string()
+        .min(1)
+        .refine((p) => p.startsWith("wiki/"), {
+        message: "Path must start with 'wiki/'",
+    })
+        .refine((p) => p.endsWith(".md"), {
+        message: "Path must end with '.md'",
+    }),
     content: z.string(),
 });
 export async function handleKnowledgeWrite(rawParams) {
@@ -31,8 +39,14 @@ export const knowledgeWriteToolSchema = {
         type: "object",
         properties: {
             project: { type: "string", description: "Project ID" },
-            path: { type: "string", description: "Relative path starting with 'wiki/', ending with .md (e.g. 'wiki/trials/sustain-6.md')" },
-            content: { type: "string", description: "Markdown content. Can include YAML frontmatter and [[wikilinks]]." },
+            path: {
+                type: "string",
+                description: "Relative path starting with 'wiki/', ending with .md (e.g. 'wiki/trials/sustain-6.md')",
+            },
+            content: {
+                type: "string",
+                description: "Markdown content. Can include YAML frontmatter and [[wikilinks]].",
+            },
         },
         required: ["project", "path", "content"],
     },

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