heor-agent-mcp 0.3.0 → 0.7.1

package/README.md

@@ -126,6 +126,50 @@ Pass `project: "project-id"` to any tool and results are saved automatically.
 
 ---
 
+## Examples
+
+Copy-paste prompts to try in Claude Code, Claude Desktop, or the [web UI](https://web-michael-ns-projects.vercel.app).
+
+### Single-tool examples
+
+**Literature search**
+> Search the literature for tirzepatide cardiovascular outcomes in type 2 diabetes. Use PubMed, ClinicalTrials.gov, and NICE TAs.
+
+**Survival curve fitting**
+> Fit survival curves to this OS data from KEYNOTE-189: time 0 survival 1.0, time 6 survival 0.88, time 12 survival 0.72, time 18 survival 0.60, time 24 survival 0.51, time 36 survival 0.38. Use months.
+
+**Budget impact**
+> Estimate the 5-year NHS budget impact of semaglutide for obesity. 200,000 eligible patients, drug cost £1,200/year, comparator (orlistat) £250/year, uptake 15% year 1 to 40% year 5.
+
+**Cost-effectiveness model**
+> Build a CE model for semaglutide vs sitagliptin in T2D, NHS perspective, lifetime horizon, with PSA.
+
+**Indirect comparison (Bucher)**
+> I have two trials: SUSTAIN-1 showed semaglutide vs placebo HR 0.74 (0.58-0.95) for HbA1c, and AWARD-5 showed dulaglutide vs placebo HR 0.78 (0.65-0.93). Run a Bucher indirect comparison between semaglutide and dulaglutide.
+
+**MAIC (population-adjusted comparison)**
+> Run a MAIC between SUSTAIN-7 (N=300, semaglutide vs placebo, HR 0.74, CI 0.58-0.95, age 56±10, BMI 33±5) and AWARD-11 (N=600, dulaglutide vs placebo, HR 0.78, CI 0.65-0.93, age 58±9, BMI 35±6). Adjust for age and BMI.
+
+### Multi-tool workflows
+
+**Abstract screening workflow**
+> Search PubMed for pembrolizumab in NSCLC, then screen the results with population adults with NSCLC, intervention pembrolizumab, comparator chemotherapy, outcomes overall survival and PFS.
+
+**Evidence network + NMA feasibility**
+> Search for GLP-1 receptor agonists in T2D using PubMed, build an evidence network from the results, and assess NMA feasibility.
+
+**CE model with scenarios**
+> Build a CE model for dapagliflozin vs placebo in heart failure, NHS perspective, lifetime horizon, with PSA. Add scenarios: "20% price reduction" with drug cost 400, "10-year horizon" with time_horizon 10yr.
+
+### End-to-end HTA workflow
+
+**Full dossier preparation**
+> Create a project for semaglutide in obesity targeting NICE and ICER. Search literature for evidence, screen the results for adults with obesity comparing semaglutide to placebo for weight loss outcomes, then draft a NICE STA dossier using the screened results.
+
+This single prompt exercises: `project_create` → `literature_search` → `screen_abstracts` → `hta_dossier_prep` (with auto-GRADE).
+
+---
+
 ## Data Sources
 
 **41 sources across 9 categories.** Every `literature_search` call includes a source selection table showing used/not-used status and reason for each.

package/dist/models/evppi.d.ts

@@ -0,0 +1,33 @@
+/**
+ * Expected Value of Partial Perfect Information (EVPPI)
+ *
+ * Per-parameter VOI analysis: shows which specific parameters are
+ * worth further research by computing how much value would be gained
+ * from resolving uncertainty in each parameter individually.
+ *
+ * Method: non-parametric regression (GAM approximation via binning)
+ * following Strong et al. (2014) "Estimating multiparameter partial
+ * expected value of perfect information from a probabilistic
+ * sensitivity analysis sample"
+ */
+export interface EVPPIResult {
+    parameter: string;
+    evppi: number;
+    evppi_proportion: number;
+}
+export interface PSAIterationData {
+    delta_cost: number;
+    delta_qaly: number;
+    params: Record<string, number>;
+}
+/**
+ * Compute EVPPI for each parameter using the binning method.
+ *
+ * For each parameter theta_j:
+ * 1. Sort iterations by theta_j
+ * 2. Bin into K groups
+ * 3. Within each bin, compute E[max_arm(NMB)]
+ * 4. EVPPI(theta_j) = E_bins[max(NMB_bin)] - max(E[NMB])
+ */
+export declare function computeEVPPI(iterations: PSAIterationData[], lambda: number, parameterNames: string[]): EVPPIResult[];
+//# sourceMappingURL=evppi.d.ts.map

package/dist/models/evppi.d.ts.map

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package/dist/models/evppi.js

@@ -0,0 +1,75 @@
+/**
+ * Expected Value of Partial Perfect Information (EVPPI)
+ *
+ * Per-parameter VOI analysis: shows which specific parameters are
+ * worth further research by computing how much value would be gained
+ * from resolving uncertainty in each parameter individually.
+ *
+ * Method: non-parametric regression (GAM approximation via binning)
+ * following Strong et al. (2014) "Estimating multiparameter partial
+ * expected value of perfect information from a probabilistic
+ * sensitivity analysis sample"
+ */
+/**
+ * Compute EVPPI for each parameter using the binning method.
+ *
+ * For each parameter theta_j:
+ * 1. Sort iterations by theta_j
+ * 2. Bin into K groups
+ * 3. Within each bin, compute E[max_arm(NMB)]
+ * 4. EVPPI(theta_j) = E_bins[max(NMB_bin)] - max(E[NMB])
+ */
+export function computeEVPPI(iterations, lambda, parameterNames) {
+    const N = iterations.length;
+    if (N < 20)
+        return [];
+    // Overall expected NMB for each arm
+    const nmb_intervention_mean = iterations.reduce((sum, it) => sum + (lambda * it.delta_qaly - it.delta_cost), 0) / N;
+    const nmb_comparator_mean = 0;
+    const max_e_nmb = Math.max(nmb_intervention_mean, nmb_comparator_mean);
+    // Total EVPI for reference
+    const e_max_nmb = iterations.reduce((sum, it) => {
+        const nmb_int = lambda * it.delta_qaly - it.delta_cost;
+        return sum + Math.max(nmb_int, 0);
+    }, 0) / N;
+    const totalEVPI = Math.max(0, e_max_nmb - max_e_nmb);
+    // Number of bins (Sturges' rule)
+    const K = Math.max(5, Math.min(30, Math.ceil(1 + 3.322 * Math.log10(N))));
+    const binSize = Math.ceil(N / K);
+    const results = [];
+    for (const paramName of parameterNames) {
+        // Check if parameter exists in iterations
+        if (iterations[0]?.params[paramName] === undefined)
+            continue;
+        // Sort by this parameter
+        const sorted = [...iterations].sort((a, b) => (a.params[paramName] ?? 0) - (b.params[paramName] ?? 0));
+        // Bin and compute conditional expectations
+        let e_max_conditional = 0;
+        for (let bin = 0; bin < K; bin++) {
+            const start = bin * binSize;
+            const end = Math.min(start + binSize, N);
+            const binN = end - start;
+            if (binN === 0)
+                continue;
+            // Expected NMB within this bin for intervention
+            let sumNMBInt = 0;
+            for (let i = start; i < end; i++) {
+                const it = sorted[i];
+                sumNMBInt += lambda * it.delta_qaly - it.delta_cost;
+            }
+            const meanNMBInt = sumNMBInt / binN;
+            // Max of conditional expectations
+            e_max_conditional += Math.max(meanNMBInt, 0) * (binN / N);
+        }
+        const evppi = Math.max(0, e_max_conditional - max_e_nmb);
+        results.push({
+            parameter: paramName,
+            evppi,
+            evppi_proportion: totalEVPI > 0 ? evppi / totalEVPI : 0,
+        });
+    }
+    // Sort by EVPPI descending
+    results.sort((a, b) => b.evppi - a.evppi);
+    return results;
+}
+//# sourceMappingURL=evppi.js.map

package/dist/models/evppi.js.map

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package/dist/models/modelUtils.d.ts

@@ -4,9 +4,14 @@
  */
 import type { CEModelParams } from "../providers/types.js";
 import type { MarkovParams } from "./markov.js";
+export declare function getTimeHorizonYears(horizon: CEModelParams["time_horizon"]): number;
 /**
- * Build MarkovParams from CEModelParams using a 2-state model
- * (On-Treatment, Off-Treatment).
+ * Build MarkovParams from CEModelParams using a 3-state model
+ * (On-Treatment, Off-Treatment, Dead).
+ *
+ * The Dead state is an absorbing state (utility=0, cost=0) — the cohort
+ * fraction that enters Dead never leaves, which correctly bounds life-year
+ * and QALY accumulation over the time horizon.
  */
 export declare function buildMarkovParamsFromCE(params: CEModelParams): MarkovParams;
 /**

package/dist/models/modelUtils.d.ts.map

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package/dist/models/modelUtils.js

@@ -4,7 +4,7 @@
  */
 import { runMarkovModel } from "./markov.js";
 const DISCOUNT_RATE = 0.035;
-function getTimeHorizonYears(horizon) {
+export function getTimeHorizonYears(horizon) {
     if (horizon === "lifetime")
         return 40;
     if (horizon === "5yr")
@@ -14,8 +14,12 @@ function getTimeHorizonYears(horizon) {
     return Number(horizon);
 }
 /**
- * Build MarkovParams from CEModelParams using a 2-state model
- * (On-Treatment, Off-Treatment).
+ * Build MarkovParams from CEModelParams using a 3-state model
+ * (On-Treatment, Off-Treatment, Dead).
+ *
+ * The Dead state is an absorbing state (utility=0, cost=0) — the cohort
+ * fraction that enters Dead never leaves, which correctly bounds life-year
+ * and QALY accumulation over the time horizon.
  */
 export function buildMarkovParamsFromCE(params) {
     const years = getTimeHorizonYears(params.time_horizon);
@@ -29,50 +33,62 @@ export function buildMarkovParamsFromCE(params) {
     const costComparator = params.cost_inputs.comparator_cost_annual +
         (params.cost_inputs.admin_cost ?? 0);
     // Efficacy delta used to derive annual probability of staying on treatment
-    // Higher efficacy → more cycles on treatment → better health
     const efficacyDelta = Math.max(0, Math.min(0.999, params.clinical_inputs.efficacy_delta));
     const mortalityReduction = params.clinical_inputs.mortality_reduction ?? 0;
-    // Transition: prob of staying in On-Treatment state for intervention
-    // Base: driven by efficacy (0.4 efficacy → ~0.8 prob of staying on treatment, modulated)
-    const probStayOnIntervention = Math.max(0.05, Math.min(0.95, 0.5 + efficacyDelta * 0.5));
-    // For comparator: lower stay probability (baseline)
-    const baselineProbStayOn = Math.max(0.05, Math.min(0.9, probStayOnIntervention * 0.7));
-    // Mortality reduction affects off-treatment → death transition
-    // (simplified: mortality reduction lowers probability of going to off-treatment)
-    const mortalityEffect = Math.max(0, Math.min(0.3, mortalityReduction * 0.3));
+    // Background annual mortality rate (~2% baseline, reduced by mortalityReduction)
+    const baseMortality = 0.02;
+    const interventionMortality = Math.max(0.005, baseMortality * (1 - mortalityReduction));
+    const comparatorMortality = baseMortality;
+    // Transition: prob of staying in On-Treatment state
+    const probStayOnIntervention = Math.max(0.05, Math.min(0.93, 0.5 + efficacyDelta * 0.5));
+    const baselineProbStayOn = Math.max(0.05, Math.min(0.88, probStayOnIntervention * 0.7));
     const states = [
         { name: "On-Treatment", utility: utilityOn, cost_annual: costIntervention },
         { name: "Off-Treatment", utility: utilityOff, cost_annual: 0 },
+        { name: "Dead", utility: 0, cost_annual: 0 },
     ];
-    const statesComparator = [
-        { name: "On-Treatment", utility: utilityOn, cost_annual: costComparator },
-        { name: "Off-Treatment", utility: utilityOff, cost_annual: 0 },
-    ];
+    // Helper: ensure row sums to 1.0
+    function normalizeRow(row) {
+        const sum = Object.values(row).reduce((a, b) => a + b, 0);
+        if (Math.abs(sum - 1.0) < 1e-10)
+            return row;
+        const result = {};
+        for (const [k, v] of Object.entries(row)) {
+            result[k] = v / sum;
+        }
+        return result;
+    }
     const transition_matrix_intervention = {
-        "On-Treatment": {
-            "On-Treatment": Math.min(0.95, probStayOnIntervention + mortalityEffect),
-            "Off-Treatment": Math.max(0.05, 1 - probStayOnIntervention - mortalityEffect),
-        },
-        "Off-Treatment": {
+        "On-Treatment": normalizeRow({
+            "On-Treatment": probStayOnIntervention,
+            "Off-Treatment": 1 - probStayOnIntervention - interventionMortality,
+            Dead: interventionMortality,
+        }),
+        "Off-Treatment": normalizeRow({
             "On-Treatment": 0.05,
-            "Off-Treatment": 0.95,
-        },
+            "Off-Treatment": 0.95 - interventionMortality,
+            Dead: interventionMortality,
+        }),
+        Dead: { "On-Treatment": 0, "Off-Treatment": 0, Dead: 1 },
     };
     const transition_matrix_comparator = {
-        "On-Treatment": {
-            "On-Treatment": Math.min(0.9, baselineProbStayOn),
-            "Off-Treatment": Math.max(0.1, 1 - baselineProbStayOn),
-        },
-        "Off-Treatment": {
+        "On-Treatment": normalizeRow({
+            "On-Treatment": baselineProbStayOn,
+            "Off-Treatment": 1 - baselineProbStayOn - comparatorMortality,
+            Dead: comparatorMortality,
+        }),
+        "Off-Treatment": normalizeRow({
             "On-Treatment": 0.05,
-            "Off-Treatment": 0.95,
-        },
+            "Off-Treatment": 0.95 - comparatorMortality,
+            Dead: comparatorMortality,
+        }),
+        Dead: { "On-Treatment": 0, "Off-Treatment": 0, Dead: 1 },
     };
     return {
         states,
         transition_matrix_intervention,
         transition_matrix_comparator,
-        initial_cohort: { "On-Treatment": 1.0, "Off-Treatment": 0.0 },
+        initial_cohort: { "On-Treatment": 1.0, "Off-Treatment": 0.0, Dead: 0.0 },
         cycle_length_years,
         n_cycles,
         discount_rate_costs: DISCOUNT_RATE,
@@ -97,10 +113,12 @@ export function runMarkovAndComputeICER(params) {
     const statesIntervention = [
         { name: "On-Treatment", utility: utilityOn, cost_annual: costIntervention },
         { name: "Off-Treatment", utility: utilityOff, cost_annual: 0 },
+        { name: "Dead", utility: 0, cost_annual: 0 },
     ];
     const statesComparator = [
         { name: "On-Treatment", utility: utilityOn, cost_annual: costComparator },
         { name: "Off-Treatment", utility: utilityOff, cost_annual: 0 },
+        { name: "Dead", utility: 0, cost_annual: 0 },
     ];
     // Run intervention arm: use intervention states + intervention transition matrix.
     // We pass intervention states in both arms' params; we only use the intervention

package/dist/models/modelUtils.js.map

@@ -1 +1 @@
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package/dist/models/psa.d.ts

@@ -2,11 +2,14 @@
  * Probabilistic Sensitivity Analysis (PSA) using Monte Carlo simulation.
  */
 import type { CEModelParams } from "../providers/types.js";
+import { type EVPPIResult } from "./evppi.js";
 export type CEModelInputs = CEModelParams;
 export interface PSAParams {
     base_params: CEModelInputs;
     n_iterations: number;
     seed?: number;
+    /** WTP threshold for EVPI calculation. Defaults to perspective-appropriate value. */
+    evpi_lambda?: number;
 }
 export interface PSAIteration {
     delta_cost: number;
@@ -24,6 +27,7 @@ export interface PSAResult {
         prob_ce: number;
     }>;
     evpi: number;
+    evppi: EVPPIResult[];
     scatter_sample: PSAIteration[];
 }
 /**

package/dist/models/psa.d.ts.map

@@ -1 +1 @@
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+{"version":3,"file":"psa.d.ts","sourceRoot":"","sources":["../../src/models/psa.ts"],"names":[],"mappings":"AAAA;;GAEG;AAEH,OAAO,KAAK,EAAE,aAAa,EAAE,MAAM,uBAAuB,CAAC;AAM3D,OAAO,EAEL,KAAK,WAAW,EAEjB,MAAM,YAAY,CAAC;AAEpB,MAAM,MAAM,aAAa,GAAG,aAAa,CAAC;AAE1C,MAAM,WAAW,SAAS;IACxB,WAAW,EAAE,aAAa,CAAC;IAC3B,YAAY,EAAE,MAAM,CAAC;IACrB,IAAI,CAAC,EAAE,MAAM,CAAC;IACd,qFAAqF;IACrF,WAAW,CAAC,EAAE,MAAM,CAAC;CACtB;AAED,MAAM,WAAW,YAAY;IAC3B,UAAU,EAAE,MAAM,CAAC;IACnB,UAAU,EAAE,MAAM,CAAC;IACnB,IAAI,EAAE,MAAM,CAAC;CACd;AAED,MAAM,WAAW,SAAS;IACxB,UAAU,EAAE,YAAY,EAAE,CAAC;IAC3B,SAAS,EAAE,MAAM,CAAC;IAClB,aAAa,EAAE,MAAM,CAAC;IACtB,aAAa,EAAE,MAAM,CAAC;IACtB,mBAAmB,EAAE,MAAM,CAAC,MAAM,EAAE,MAAM,CAAC,CAAC;IAC5C,IAAI,EAAE,KAAK,CAAC;QAAE,GAAG,EAAE,MAAM,CAAC;QAAC,OAAO,EAAE,MAAM,CAAA;KAAE,CAAC,CAAC;IAC9C,IAAI,EAAE,MAAM,CAAC;IACb,KAAK,EAAE,WAAW,EAAE,CAAC;IACrB,cAAc,EAAE,YAAY,EAAE,CAAC;CAChC;AAiCD;;GAEG;AACH,wBAAgB,MAAM,CAAC,MAAM,EAAE,SAAS,GAAG,SAAS,CA8KnD"}

package/dist/models/psa.js

@@ -3,6 +3,7 @@
  */
 import { betaSample, gammaSample, createSeededRng } from "./distributions.js";
 import { runMarkovAndComputeICER, } from "./modelUtils.js";
+import { computeEVPPI, } from "./evppi.js";
 const WTP_THRESHOLDS_PSA = {
     nhs_low: 25000,
     nhs_high: 35000,
@@ -37,6 +38,7 @@ function perturbGamma(value, cv, rng) {
 export function runPSA(params) {
     const rng = createSeededRng(params.seed ?? 42);
     const iterations = [];
+    const evppiData = [];
     for (let i = 0; i < params.n_iterations; i++) {
         // Sample perturbed parameters
         const perturbedParams = {
@@ -67,6 +69,27 @@ export function runPSA(params) {
         };
         const { delta_cost, delta_qaly, icer } = runMarkovAndComputeICER(perturbedParams);
         iterations.push({ delta_cost, delta_qaly, icer });
+        // Track parameter values for EVPPI
+        evppiData.push({
+            delta_cost,
+            delta_qaly,
+            params: {
+                efficacy_delta: perturbedParams.clinical_inputs.efficacy_delta,
+                drug_cost_annual: perturbedParams.cost_inputs.drug_cost_annual,
+                comparator_cost_annual: perturbedParams.cost_inputs.comparator_cost_annual,
+                ...(perturbedParams.clinical_inputs.mortality_reduction !== undefined
+                    ? {
+                        mortality_reduction: perturbedParams.clinical_inputs.mortality_reduction,
+                    }
+                    : {}),
+                ...(perturbedParams.utility_inputs
+                    ? {
+                        qaly_on_treatment: perturbedParams.utility_inputs.qaly_on_treatment,
+                        qaly_comparator: perturbedParams.utility_inputs.qaly_comparator,
+                    }
+                    : {}),
+            },
+        });
     }
     // Compute statistics
     const finiteICERs = iterations
@@ -96,8 +119,8 @@ export function runPSA(params) {
         ceac.push({ wtp, prob_ce: n_ce / iterations.length });
     }
     // EVPI: E[max_arm(NMB)] - max_arm(E[NMB])
-    // Using a reference WTP (midpoint of common thresholds: $50,000)
-    const lambda = 50000;
+    // Use perspective-appropriate WTP threshold (passed via evpi_lambda)
+    const lambda = params.evpi_lambda ?? 50000;
     const nmb_intervention_mean = iterations.reduce((sum, it) => sum + (lambda * it.delta_qaly - it.delta_cost), 0) / iterations.length;
     const nmb_comparator_mean = 0; // comparator is reference (delta = 0)
     const e_max_nmb = iterations.reduce((sum, it) => {
@@ -106,6 +129,9 @@ export function runPSA(params) {
     }, 0) / iterations.length;
     const max_e_nmb = Math.max(nmb_intervention_mean, nmb_comparator_mean);
     const evpi = Math.max(0, e_max_nmb - max_e_nmb);
+    // EVPPI: per-parameter partial value of information
+    const paramNames = evppiData.length > 0 ? Object.keys(evppiData[0].params) : [];
+    const evppiResults = computeEVPPI(evppiData, lambda, paramNames);
     const scatter_sample = iterations.slice(0, 500);
     return {
         iterations,
@@ -115,6 +141,7 @@ export function runPSA(params) {
         prob_cost_effective,
         ceac,
         evpi,
+        evppi: evppiResults,
         scatter_sample,
     };
 }

package/dist/models/psa.js.map

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package/dist/models/survivalFitting.d.ts

@@ -0,0 +1,47 @@
+/**
+ * Survival Curve Fitting — fit parametric distributions to Kaplan-Meier data.
+ *
+ * Supports: Exponential, Weibull, Log-logistic, Log-normal, Gompertz.
+ * Uses maximum likelihood estimation via Newton-Raphson optimization.
+ * Model selection via AIC/BIC.
+ *
+ * References:
+ * - Latimer NR. NICE DSU TSD 14: Survival analysis (2013)
+ * - Collett D. Modelling Survival Data in Medical Research (2015)
+ */
+export interface KMDataPoint {
+    time: number;
+    survival: number;
+    n_at_risk?: number;
+    n_events?: number;
+}
+export type DistributionName = "exponential" | "weibull" | "log_logistic" | "log_normal" | "gompertz";
+export interface FittedDistribution {
+    name: DistributionName;
+    params: Record<string, number>;
+    aic: number;
+    bic: number;
+    log_likelihood: number;
+    survival_at: (t: number) => number;
+    hazard_at: (t: number) => number;
+    median_survival: number;
+    mean_survival_restricted: number;
+}
+export interface SurvivalFitResult {
+    fits: FittedDistribution[];
+    best_aic: FittedDistribution;
+    best_bic: FittedDistribution;
+    km_data: KMDataPoint[];
+    time_unit: string;
+    extrapolations: Array<{
+        time: number;
+        km_observed?: number;
+        exponential: number;
+        weibull: number;
+        log_logistic: number;
+        log_normal: number;
+        gompertz: number;
+    }>;
+}
+export declare function fitSurvivalCurves(data: KMDataPoint[], timeUnit?: string): SurvivalFitResult;
+//# sourceMappingURL=survivalFitting.d.ts.map

package/dist/models/survivalFitting.d.ts.map

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