/**
 * Machine Learning Outcome Prediction Infrastructure
 *
 * Provides ML-based prediction models for:
 * - Treatment response prediction
 * - Survival probability estimation
 * - Toxicity risk assessment
 * - Resistance prediction
 * - Optimal therapy selection
 *
 * This module provides the infrastructure for training and deploying
 * ML models. In production, models would be trained on real patient cohorts
 * with proper validation and FDA clearance.
 */
import { EventEmitter } from 'events';
export interface PatientFeatures {
    age: number;
    gender: 'male' | 'female';
    ethnicity?: string;
    bmi?: number;
    cancerType: string;
    histology?: string;
    stage: 'I' | 'II' | 'III' | 'IV' | 'IA' | 'IB' | 'IIA' | 'IIB' | 'IIIA' | 'IIIB' | 'IIIC' | 'IVA' | 'IVB';
    grade?: 1 | 2 | 3;
    tumorSize?: number;
    lymphNodeInvolvement?: number;
    metastaticSites?: string[];
    ecogStatus: 0 | 1 | 2 | 3 | 4;
    genomicAlterations: {
        gene: string;
        alteration: string;
        type: 'mutation' | 'amplification' | 'deletion' | 'fusion';
        vaf?: number;
    }[];
    pdl1Score?: number;
    pdl1ScoreType?: 'TPS' | 'CPS' | 'IC';
    msiStatus?: 'MSI-H' | 'MSI-L' | 'MSS';
    tmbValue?: number;
    tmbStatus?: 'high' | 'low';
    hrdScore?: number;
    hrdStatus?: 'positive' | 'negative';
    brcaStatus?: 'BRCA1' | 'BRCA2' | 'wild-type';
    ldh?: number;
    albumin?: number;
    hemoglobin?: number;
    neutrophils?: number;
    lymphocytes?: number;
    platelets?: number;
    creatinine?: number;
    bilirubin?: number;
    alkalinePhosphatase?: number;
    priorLines?: number;
    priorTherapies?: string[];
    priorResponse?: 'CR' | 'PR' | 'SD' | 'PD';
    treatmentFreeInterval?: number;
    comorbidityIndex?: number;
    organFunction?: {
        cardiac?: 'normal' | 'impaired';
        hepatic?: 'normal' | 'impaired';
        renal?: 'normal' | 'impaired';
        pulmonary?: 'normal' | 'impaired';
    };
}
export interface TreatmentFeatures {
    regimen: string;
    drugs: string[];
    treatmentType: 'chemotherapy' | 'immunotherapy' | 'targeted' | 'combination' | 'radiation' | 'surgery' | 'car-t';
    setting: 'neoadjuvant' | 'adjuvant' | 'first-line' | 'second-line' | 'third-line-plus' | 'maintenance';
    dosing?: 'standard' | 'reduced' | 'dose-dense';
    schedule?: string;
}
export interface ResponsePrediction {
    predictedResponse: 'CR' | 'PR' | 'SD' | 'PD';
    probabilities: {
        completeResponse: number;
        partialResponse: number;
        stableDisease: number;
        progressiveDisease: number;
    };
    confidence: number;
    objectiveResponseRate: number;
    diseaseControlRate: number;
    timeToResponse?: {
        median: number;
        range: [number, number];
    };
}
export interface SurvivalPrediction {
    pfs: {
        median: number;
        sixMonth: number;
        twelveMonth: number;
        twentyFourMonth: number;
        confidence: number;
        hazardRatio?: number;
    };
    os: {
        median: number;
        twelveMonth: number;
        twentyFourMonth: number;
        fiveYear: number;
        confidence: number;
        hazardRatio?: number;
    };
    riskGroup: 'low' | 'intermediate-low' | 'intermediate-high' | 'high';
    riskScore: number;
}
export interface ToxicityPrediction {
    overallRisk: 'low' | 'moderate' | 'high';
    grade3PlusRisk: number;
    specificRisks: {
        toxicity: string;
        grade: 1 | 2 | 3 | 4 | 5;
        probability: number;
        timeToOnset?: {
            median: number;
            unit: 'days' | 'weeks' | 'cycles';
        };
        reversible: boolean;
        management?: string;
    }[];
    iraeRisk?: {
        any: number;
        grade3Plus: number;
        specificOrgans: {
            organ: string;
            risk: number;
        }[];
    };
    doseModification?: {
        recommended: boolean;
        reduction: number;
        reason: string;
    };
}
export interface ResistancePrediction {
    intrinsicResistanceRisk: number;
    acquiredResistanceRisk: number;
    predictedMechanisms: {
        mechanism: string;
        probability: number;
        monitoringBiomarker?: string;
    }[];
    timeToResistance?: {
        median: number;
        range: [number, number];
    };
    nextLineOptions: {
        therapy: string;
        rationale: string;
        expectedBenefit: number;
    }[];
}
export interface TherapyRanking {
    therapies: {
        regimen: string;
        drugs: string[];
        rank: number;
        predictions: {
            responseRate: number;
            pfsSurvival: number;
            osSurvival: number;
            toxicityRisk: number;
            qualityOfLifeScore: number;
        };
        overallScore: number;
        confidence: number;
        matchingBiomarkers: string[];
        fdaApproved: boolean;
        nccnRecommended: boolean;
        considerations: string[];
        contraindications?: string[];
    }[];
    bestChoice: {
        regimen: string;
        rationale: string[];
    };
}
export interface MLModel {
    id: string;
    name: string;
    version: string;
    type: 'classification' | 'regression' | 'survival' | 'ranking';
    target: 'response' | 'pfs' | 'os' | 'toxicity' | 'resistance';
    cancerTypes: string[];
    performance: {
        auc?: number;
        accuracy?: number;
        sensitivity?: number;
        specificity?: number;
        cIndex?: number;
        calibration?: number;
        brier?: number;
    };
    validation: {
        method: 'cross-validation' | 'temporal' | 'external' | 'prospective';
        cohortSize: number;
        testSetSize: number;
        validationDate: Date;
    };
    features: string[];
    importantFeatures: {
        feature: string;
        importance: number;
    }[];
    status: 'development' | 'validation' | 'clinical-use' | 'deprecated';
    regulatoryStatus?: 'not-submitted' | 'pending' | 'cleared' | '510k' | 'de-novo';
}
export interface ModelRegistry {
    models: MLModel[];
    getModel(id: string): MLModel | undefined;
    getBestModel(target: MLModel['target'], cancerType: string): MLModel | undefined;
    registerModel(model: MLModel): void;
}
export declare class OutcomePredictorService extends EventEmitter {
    private modelRegistry;
    private featureEncoders;
    private predictionCache;
    private cacheDuration;
    constructor();
    /**
     * Predict treatment response
     */
    predictResponse(patient: PatientFeatures, treatment: TreatmentFeatures): Promise<ResponsePrediction>;
    /**
     * Predict survival outcomes
     */
    predictSurvival(patient: PatientFeatures, treatment: TreatmentFeatures): Promise<SurvivalPrediction>;
    /**
     * Predict toxicity risk
     */
    predictToxicity(patient: PatientFeatures, treatment: TreatmentFeatures): Promise<ToxicityPrediction>;
    /**
     * Predict resistance development
     */
    predictResistance(patient: PatientFeatures, treatment: TreatmentFeatures): Promise<ResistancePrediction>;
    /**
     * Rank treatment options
     */
    rankTherapies(patient: PatientFeatures, treatmentOptions: TreatmentFeatures[], preferences?: {
        prioritizeEfficacy?: boolean;
        prioritizeToxicity?: boolean;
        prioritizeQoL?: boolean;
    }): Promise<TherapyRanking>;
    /**
     * Get comprehensive prediction report
     */
    getComprehensivePrediction(patient: PatientFeatures, treatment: TreatmentFeatures): Promise<{
        response: ResponsePrediction;
        survival: SurvivalPrediction;
        toxicity: ToxicityPrediction;
        resistance: ResistancePrediction;
        overallAssessment: {
            recommendation: 'strongly-recommended' | 'recommended' | 'consider' | 'caution' | 'not-recommended';
            rationale: string[];
            caveats: string[];
            alternativeOptions: string[];
        };
    }>;
    private computeResponsePrediction;
    private computeSurvivalPrediction;
    private computeToxicityPrediction;
    private computeResistancePrediction;
    private initializeDefaultModels;
    private initializeFeatureEncoders;
    private encodeFeatures;
    private getBestModel;
    private hasBiomarkerMatch;
    private hasImmunotherapyDrug;
    private getDrugToxicityProfiles;
    private getResistanceMechanisms;
    private getNextLineOptions;
    private estimateQoLScore;
    private getMatchingBiomarkers;
    private isBiomarkerRelevant;
    private checkFDAApproval;
    private checkNCCNRecommendation;
    private getConsiderations;
    private generateOverallAssessment;
    private getCacheKey;
    private getFromCache;
    private setCache;
    /**
     * Register a new model
     */
    registerModel(model: MLModel): void;
    /**
     * Get model performance metrics
     */
    getModelMetrics(modelId: string): MLModel['performance'] | undefined;
    /**
     * List all available models
     */
    listModels(): MLModel[];
}
export default OutcomePredictorService;
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