heor-agent-mcp 0.1.7 → 0.3.0

package/dist/formatters/comparisonMarkdown.d.ts

@@ -0,0 +1,3 @@
+import type { IndirectComparisonResult } from "../network/types.js";
+export declare function comparisonToMarkdown(result: IndirectComparisonResult): string;
+//# sourceMappingURL=comparisonMarkdown.d.ts.map

package/dist/formatters/comparisonMarkdown.d.ts.map

@@ -0,0 +1 @@
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package/dist/formatters/comparisonMarkdown.js

@@ -0,0 +1,68 @@
+function formatNum(n, decimals = 2) {
+    return n.toFixed(decimals);
+}
+function formatP(p) {
+    if (p < 0.001)
+        return "<0.001";
+    if (p < 0.01)
+        return formatNum(p, 3);
+    return formatNum(p, 3);
+}
+export function comparisonToMarkdown(result) {
+    const lines = [];
+    lines.push("## Indirect Treatment Comparisons");
+    lines.push("");
+    const methodLabel = result.method === "bucher"
+        ? "Bucher Method"
+        : result.method === "frequentist_nma"
+            ? "Frequentist Network Meta-Analysis"
+            : "Mixed Methods";
+    lines.push(`**Method:** ${methodLabel}`);
+    lines.push(`**Comparisons:** ${result.estimates.length}`);
+    lines.push("");
+    if (result.estimates.length === 0) {
+        lines.push("No indirect comparisons could be computed. Check that comparisons share a common comparator and measure the same outcome.");
+        return lines.join("\n");
+    }
+    // Group by outcome
+    const outcomes = new Map();
+    for (const e of result.estimates) {
+        if (!outcomes.has(e.outcome))
+            outcomes.set(e.outcome, []);
+        outcomes.get(e.outcome).push(e);
+    }
+    for (const [outcome, estimates] of outcomes) {
+        lines.push(`### ${outcome}`);
+        lines.push("");
+        const measure = estimates[0].measure;
+        const label = measure === "MD" ? "MD" : measure;
+        lines.push(`| Comparison | ${label} | 95% CI | p-value | Via | Method |`);
+        lines.push("|------------|---------|--------|---------|-----|--------|");
+        for (const e of estimates) {
+            const est = measure === "MD"
+                ? formatNum(e.estimate)
+                : formatNum(e.estimate);
+            const ci = `[${formatNum(e.ci_lower)}, ${formatNum(e.ci_upper)}]`;
+            const p = formatP(e.p_value);
+            const via = e.commonComparator;
+            const method = e.method === "bucher" ? "Bucher" : "Freq. NMA";
+            lines.push(`| ${e.intervention} vs ${e.comparator} | ${est} | ${ci} | ${p} | ${via} | ${method} |`);
+        }
+        lines.push("");
+    }
+    // Warnings
+    if (result.warnings.length > 0) {
+        lines.push("### Warnings");
+        for (const w of result.warnings) {
+            lines.push(`- ⚠️ ${w}`);
+        }
+        lines.push("");
+    }
+    // Limitations
+    lines.push("### Limitations");
+    for (const l of result.limitations) {
+        lines.push(`- ${l}`);
+    }
+    return lines.join("\n");
+}
+//# sourceMappingURL=comparisonMarkdown.js.map

package/dist/formatters/comparisonMarkdown.js.map

@@ -0,0 +1 @@
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package/dist/formatters/networkMarkdown.d.ts

@@ -0,0 +1,3 @@
+import type { EvidenceNetwork } from "../network/types.js";
+export declare function networkToMarkdown(network: EvidenceNetwork): string;
+//# sourceMappingURL=networkMarkdown.d.ts.map

package/dist/formatters/networkMarkdown.d.ts.map

@@ -0,0 +1 @@
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package/dist/formatters/networkMarkdown.js

@@ -0,0 +1,74 @@
+export function networkToMarkdown(network) {
+    const lines = [];
+    lines.push("## Evidence Network Analysis");
+    lines.push("");
+    // Summary
+    const { feasibility } = network;
+    const verdict = feasibility.feasible ? "**Feasible**" : "**Not feasible**";
+    lines.push(`**NMA Feasibility:** ${verdict}`);
+    lines.push(`**Treatments:** ${feasibility.nodeCount} | **Comparisons:** ${feasibility.edgeCount} | **Connected:** ${feasibility.connected ? "Yes" : "No"}`);
+    lines.push("");
+    // Reasons
+    lines.push("### Assessment");
+    for (const reason of feasibility.reasons) {
+        const icon = reason.includes("not") || reason.includes("Only") || reason.includes("disconnected")
+            ? "⚠️"
+            : "✓";
+        lines.push(`- ${icon} ${reason}`);
+    }
+    lines.push("");
+    // Network graph (text)
+    if (network.edges.length > 0) {
+        lines.push("### Evidence Network");
+        lines.push("| Comparison | Trials | Study Types | Confidence |");
+        lines.push("|------------|--------|-------------|------------|");
+        for (const edge of network.edges) {
+            const sourceNode = network.nodes.find((n) => n.id === edge.source);
+            const targetNode = network.nodes.find((n) => n.id === edge.target);
+            const source = sourceNode?.label ?? edge.source;
+            const target = targetNode?.label ?? edge.target;
+            const types = [...new Set(edge.studyTypes)].join(", ");
+            lines.push(`| ${source} ↔ ${target} | ${edge.trials.length} | ${types} | ${edge.confidence} |`);
+        }
+        lines.push("");
+    }
+    // Nodes
+    if (network.nodes.length > 0) {
+        lines.push("### Treatments Identified");
+        lines.push("| Treatment | Role |");
+        lines.push("|-----------|------|");
+        for (const node of network.nodes) {
+            lines.push(`| ${node.label} | ${node.type} |`);
+        }
+        lines.push("");
+    }
+    // Components (if disconnected)
+    if (feasibility.componentCount > 1) {
+        lines.push("### Disconnected Components");
+        for (let i = 0; i < feasibility.components.length; i++) {
+            lines.push(`- **Component ${i + 1}:** ${feasibility.components[i].join(", ")}`);
+        }
+        lines.push("");
+    }
+    // Gaps
+    if (feasibility.gaps.length > 0) {
+        lines.push("### Evidence Gaps");
+        for (const gap of feasibility.gaps) {
+            lines.push(`- ⚠️ ${gap.description}`);
+        }
+        lines.push("");
+    }
+    // Recommendation
+    lines.push("### Recommendation");
+    if (feasibility.feasible) {
+        lines.push("The evidence network is connected with sufficient comparisons to support a network meta-analysis. " +
+            "Consider Bayesian NMA (R/Stan or WinBUGS) with assessment of heterogeneity and inconsistency.");
+    }
+    else {
+        lines.push("The evidence network does not currently support a valid NMA. " +
+            "Consider: expanding the literature search, including indirect comparators, " +
+            "or using pairwise meta-analysis for available direct comparisons.");
+    }
+    return lines.join("\n");
+}
+//# sourceMappingURL=networkMarkdown.js.map

package/dist/formatters/networkMarkdown.js.map

@@ -0,0 +1 @@
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package/dist/network/bucher.d.ts

@@ -0,0 +1,29 @@
+import type { EffectMeasure, PooledEstimate, DirectComparison, IndirectEstimate } from "./types.js";
+/** Standard error from 95% CI */
+export declare function seFromCI(lower: number, upper: number): number;
+/** Normal CDF approximation (Abramowitz & Stegun 26.2.17) */
+export declare function normalCDF(x: number): number;
+/** Two-tailed p-value from z-score */
+export declare function pValueFromZ(z: number): number;
+/** Fixed-effect inverse-variance pooling */
+export declare function poolFixedEffect(studies: Array<{
+    value: number;
+    se: number;
+}>): PooledEstimate;
+/** Bucher indirect comparison: A vs C = A vs B - C vs B */
+export declare function bucherIndirect(ab: PooledEstimate, cb: PooledEstimate): {
+    value: number;
+    se: number;
+    z: number;
+    p_value: number;
+};
+/**
+ * Compute a single indirect comparison A vs C through common comparator B.
+ *
+ * directAB: studies comparing A (intervention) vs B (comparator)
+ * directCB: studies comparing C (intervention) vs B (comparator)
+ *
+ * Returns the indirect estimate of A vs C.
+ */
+export declare function computeIndirectComparison(intervention: string, comparator: string, bridge: string, directAB: DirectComparison[], directCB: DirectComparison[], outcome: string, measure: EffectMeasure): IndirectEstimate;
+//# sourceMappingURL=bucher.d.ts.map

package/dist/network/bucher.d.ts.map

@@ -0,0 +1 @@
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package/dist/network/bucher.js

@@ -0,0 +1,125 @@
+/** Standard error from 95% CI */
+export function seFromCI(lower, upper) {
+    return (upper - lower) / 3.92;
+}
+/** Normal CDF approximation (Abramowitz & Stegun 26.2.17) */
+export function normalCDF(x) {
+    const sign = x < 0 ? -1 : 1;
+    const z = Math.abs(x);
+    const t = 1.0 / (1.0 + 0.2316419 * z);
+    const d = 0.3989422804014327; // 1/sqrt(2*pi)
+    const p = d *
+        Math.exp((-z * z) / 2.0) *
+        (t *
+            (0.319381530 +
+                t *
+                    (-0.356563782 +
+                        t * (1.781477937 + t * (-1.821255978 + t * 1.330274429)))));
+    return sign === 1 ? 1.0 - p : p;
+}
+/** Two-tailed p-value from z-score */
+export function pValueFromZ(z) {
+    return 2 * (1 - normalCDF(Math.abs(z)));
+}
+/** Whether the measure operates on a log scale */
+function isLogScale(measure) {
+    return measure === "OR" || measure === "RR" || measure === "HR";
+}
+/** Convert to working scale (log for ratio measures) */
+function toWorkingScale(estimate, se, measure) {
+    if (isLogScale(measure)) {
+        return { value: Math.log(estimate), se };
+    }
+    return { value: estimate, se };
+}
+/** Convert SE from CI on the original scale to working scale */
+function seOnWorkingScale(estimate, ci_lower, ci_upper, measure) {
+    if (isLogScale(measure)) {
+        return (Math.log(ci_upper) - Math.log(ci_lower)) / 3.92;
+    }
+    return seFromCI(ci_lower, ci_upper);
+}
+/** Back-transform from working scale */
+function fromWorkingScale(value, lower, upper, measure) {
+    if (isLogScale(measure)) {
+        return {
+            estimate: Math.exp(value),
+            ci_lower: Math.exp(lower),
+            ci_upper: Math.exp(upper),
+        };
+    }
+    return { estimate: value, ci_lower: lower, ci_upper: upper };
+}
+/** Fixed-effect inverse-variance pooling */
+export function poolFixedEffect(studies) {
+    if (studies.length === 0) {
+        throw new Error("No studies to pool");
+    }
+    if (studies.length === 1) {
+        return { value: studies[0].value, se: studies[0].se, n_studies: 1 };
+    }
+    let sumW = 0;
+    let sumWY = 0;
+    for (const s of studies) {
+        const w = 1 / (s.se * s.se);
+        sumW += w;
+        sumWY += w * s.value;
+    }
+    return {
+        value: sumWY / sumW,
+        se: Math.sqrt(1 / sumW),
+        n_studies: studies.length,
+    };
+}
+/** Bucher indirect comparison: A vs C = A vs B - C vs B */
+export function bucherIndirect(ab, cb) {
+    const value = ab.value - cb.value;
+    const se = Math.sqrt(ab.se * ab.se + cb.se * cb.se);
+    const z = value / se;
+    const p_value = pValueFromZ(z);
+    return { value, se, z, p_value };
+}
+/**
+ * Compute a single indirect comparison A vs C through common comparator B.
+ *
+ * directAB: studies comparing A (intervention) vs B (comparator)
+ * directCB: studies comparing C (intervention) vs B (comparator)
+ *
+ * Returns the indirect estimate of A vs C.
+ */
+export function computeIndirectComparison(intervention, comparator, bridge, directAB, directCB, outcome, measure) {
+    // Convert to working scale and pool
+    const abStudies = directAB.map((d) => ({
+        value: toWorkingScale(d.estimate, seOnWorkingScale(d.estimate, d.ci_lower, d.ci_upper, measure), measure).value,
+        se: seOnWorkingScale(d.estimate, d.ci_lower, d.ci_upper, measure),
+    }));
+    const cbStudies = directCB.map((d) => ({
+        value: toWorkingScale(d.estimate, seOnWorkingScale(d.estimate, d.ci_lower, d.ci_upper, measure), measure).value,
+        se: seOnWorkingScale(d.estimate, d.ci_lower, d.ci_upper, measure),
+    }));
+    const pooledAB = poolFixedEffect(abStudies);
+    const pooledCB = poolFixedEffect(cbStudies);
+    // Bucher indirect
+    const indirect = bucherIndirect(pooledAB, pooledCB);
+    // Back-transform
+    const ciLowerWorking = indirect.value - 1.96 * indirect.se;
+    const ciUpperWorking = indirect.value + 1.96 * indirect.se;
+    const result = fromWorkingScale(indirect.value, ciLowerWorking, ciUpperWorking, measure);
+    return {
+        intervention,
+        comparator,
+        commonComparator: bridge,
+        outcome,
+        measure,
+        method: "bucher",
+        estimate: result.estimate,
+        se: indirect.se,
+        ci_lower: result.ci_lower,
+        ci_upper: result.ci_upper,
+        z: indirect.z,
+        p_value: indirect.p_value,
+        pooled_ab: pooledAB,
+        pooled_bc: pooledCB,
+    };
+}
+//# sourceMappingURL=bucher.js.map

package/dist/network/bucher.js.map

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package/dist/network/builder.d.ts

@@ -0,0 +1,3 @@
+import type { EvidenceNetwork, ComparatorPair } from "./types.js";
+export declare function buildEvidenceNetwork(pairs: ComparatorPair[]): EvidenceNetwork;
+//# sourceMappingURL=builder.d.ts.map

package/dist/network/builder.d.ts.map

@@ -0,0 +1 @@
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package/dist/network/builder.js

@@ -0,0 +1,155 @@
+import { normalizeDrugName } from "./extractor.js";
+// Union-Find for connected components
+class UnionFind {
+    parent = new Map();
+    find(x) {
+        if (!this.parent.has(x))
+            this.parent.set(x, x);
+        const p = this.parent.get(x);
+        if (p !== x) {
+            const root = this.find(p);
+            this.parent.set(x, root);
+            return root;
+        }
+        return x;
+    }
+    union(a, b) {
+        const ra = this.find(a);
+        const rb = this.find(b);
+        if (ra !== rb)
+            this.parent.set(ra, rb);
+    }
+    components() {
+        const groups = new Map();
+        for (const key of this.parent.keys()) {
+            const root = this.find(key);
+            if (!groups.has(root))
+                groups.set(root, []);
+            groups.get(root).push(key);
+        }
+        return groups;
+    }
+}
+export function buildEvidenceNetwork(pairs) {
+    // Build nodes
+    const nodeMap = new Map();
+    const edgeMap = new Map();
+    for (const pair of pairs) {
+        const intId = normalizeDrugName(pair.intervention);
+        const compId = normalizeDrugName(pair.comparator);
+        if (!nodeMap.has(intId)) {
+            nodeMap.set(intId, {
+                id: intId,
+                label: pair.intervention,
+                type: "intervention",
+            });
+        }
+        if (!nodeMap.has(compId)) {
+            nodeMap.set(compId, {
+                id: compId,
+                label: pair.comparator,
+                type: "comparator",
+            });
+        }
+        // Edge key is sorted to avoid duplicates (A→B = B→A)
+        const edgeKey = [intId, compId].sort().join("↔");
+        if (!edgeMap.has(edgeKey)) {
+            edgeMap.set(edgeKey, {
+                source: intId,
+                target: compId,
+                trials: [],
+                studyTypes: [],
+                direct: true,
+                confidence: pair.confidence,
+            });
+        }
+        const edge = edgeMap.get(edgeKey);
+        if (!edge.trials.includes(pair.trialId)) {
+            edge.trials.push(pair.trialId);
+            edge.studyTypes.push(pair.studyType);
+        }
+        // Upgrade confidence if higher
+        if (pair.confidence === "high" ||
+            (pair.confidence === "medium" && edge.confidence === "low")) {
+            edge.confidence = pair.confidence;
+        }
+    }
+    const nodes = Array.from(nodeMap.values());
+    const edges = Array.from(edgeMap.values());
+    // Connectivity analysis
+    const uf = new UnionFind();
+    for (const node of nodes) {
+        uf.find(node.id); // register
+    }
+    for (const edge of edges) {
+        uf.union(edge.source, edge.target);
+    }
+    const componentMap = uf.components();
+    const components = Array.from(componentMap.values()).filter((c) => c.length > 0);
+    const connected = components.length === 1;
+    // Find gaps: pairs of nodes in different components
+    const gaps = [];
+    if (!connected && components.length >= 2) {
+        for (let i = 0; i < components.length - 1; i++) {
+            for (let j = i + 1; j < components.length; j++) {
+                const nodeA = nodeMap.get(components[i][0]);
+                const nodeB = nodeMap.get(components[j][0]);
+                if (nodeA && nodeB) {
+                    gaps.push({
+                        from: nodeA.label,
+                        to: nodeB.label,
+                        description: `No direct or indirect evidence path between "${nodeA.label}" network and "${nodeB.label}" network`,
+                    });
+                }
+            }
+        }
+    }
+    const minTrialsPerEdge = edges.length > 0 ? Math.min(...edges.map((e) => e.trials.length)) : 0;
+    // Feasibility assessment
+    const reasons = [];
+    let feasible = true;
+    if (nodes.length < 3) {
+        reasons.push(`Only ${nodes.length} treatments identified — NMA requires at least 3`);
+        feasible = false;
+    }
+    else {
+        reasons.push(`${nodes.length} treatments identified`);
+    }
+    if (!connected) {
+        reasons.push(`Network is disconnected (${components.length} components) — NMA requires a connected network`);
+        feasible = false;
+    }
+    else {
+        reasons.push("Network is fully connected");
+    }
+    if (minTrialsPerEdge < 1) {
+        reasons.push("Some comparisons have no supporting trials");
+        feasible = false;
+    }
+    else if (minTrialsPerEdge < 2) {
+        reasons.push("Some comparisons have only 1 trial — consider heterogeneity carefully");
+    }
+    else {
+        reasons.push(`All comparisons supported by ≥${minTrialsPerEdge} trials`);
+    }
+    if (edges.length < 2) {
+        reasons.push(`Only ${edges.length} comparison(s) found — NMA adds value with ≥3 comparisons`);
+        feasible = false;
+    }
+    else {
+        reasons.push(`${edges.length} direct comparisons found`);
+    }
+    const feasibility = {
+        feasible,
+        reasons,
+        nodeCount: nodes.length,
+        edgeCount: edges.length,
+        connected,
+        componentCount: components.length,
+        components: components.map((c) => c.map((id) => nodeMap.get(id)?.label ?? id)),
+        minTrialsPerEdge,
+        gaps,
+    };
+    return { nodes, edges, feasibility };
+}
+//# sourceMappingURL=builder.js.map

package/dist/network/builder.js.map

@@ -0,0 +1 @@
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package/dist/network/extractor.d.ts

@@ -0,0 +1,5 @@
+import type { LiteratureResult } from "../providers/types.js";
+import type { ComparatorPair } from "./types.js";
+export declare function normalizeDrugName(name: string): string;
+export declare function extractComparatorPairs(results: LiteratureResult[]): ComparatorPair[];
+//# sourceMappingURL=extractor.d.ts.map

package/dist/network/extractor.d.ts.map

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