/**
 * Real-World Oncology Orchestration Service
 *
 * ██████╗ ███████╗ █████╗ ██╗         ██╗    ██╗ ██████╗ ██████╗ ██╗     ██████╗
 * ██╔══██╗██╔════╝██╔══██╗██║         ██║    ██║██╔═══██╗██╔══██╗██║     ██╔══██╗
 * ██████╔╝█████╗  ███████║██║         ██║ █╗ ██║██║   ██║██████╔╝██║     ██║  ██║
 * ██╔══██╗██╔══╝  ██╔══██║██║         ██║███╗██║██║   ██║██╔══██╗██║     ██║  ██║
 * ██║  ██║███████╗██║  ██║███████╗    ╚███╔███╔╝╚██████╔╝██║  ██║███████╗██████╔╝
 * ╚═╝  ╚═╝╚══════╝╚═╝  ╚═╝╚══════╝     ╚══╝╚══╝  ╚═════╝ ╚═╝  ╚═╝╚══════╝╚═════╝
 *  ██████╗ ███╗   ██╗ ██████╗ ██████╗ ██╗      ██████╗  ██████╗██╗   ██╗
 * ██╔═══██╗████╗  ██║██╔════╝██╔═══██╗██║     ██╔═══██╗██╔════╝╚██╗ ██╔╝
 * ██║   ██║██╔██╗ ██║██║     ██║   ██║██║     ██║   ██║██║  ███╗╚████╔╝
 * ██║   ██║██║╚██╗██║██║     ██║   ██║██║     ██║   ██║██║   ██║ ╚██╔╝
 * ╚██████╔╝██║ ╚████║╚██████╗╚██████╔╝███████╗╚██████╔╝╚██████╔╝  ██║
 *  ╚═════╝ ╚═╝  ╚═══╝ ╚═════╝ ╚═════╝ ╚══════╝ ╚═════╝  ╚═════╝   ╚═╝
 *
 * This service orchestrates all components of the real-world precision oncology system:
 * - EHR Integration (Epic, Cerner via HL7 FHIR)
 * - Genomic Platforms (Foundation Medicine, Guardant Health, Tempus)
 * - Clinical Trials (ClinicalTrials.gov)
 * - HIPAA Compliance (Audit, Consent, Encryption, Access Control)
 * - ML Outcome Prediction (Response, Survival, Toxicity, Resistance)
 * - Drug Safety (Interactions, Contraindications, Pharmacogenomics)
 * - Validation Framework (Retrospective validation, Concordance analysis)
 * - Clinician Decision Support (Recommendations, Overrides, Tumor Board)
 * - Patient Portal (Symptoms, Adherence, QoL, Messaging)
 */
import { CancerCureResult } from '../capabilities/cancerTreatmentCapability.js';
export interface RealWorldConfig {
    ehr: {
        enabled: boolean;
        vendor: 'epic' | 'cerner' | 'other';
        baseUrl: string;
        clientId: string;
        clientSecret?: string;
    };
    genomics: {
        enabled: boolean;
        platforms: ('foundation' | 'guardant' | 'tempus')[];
    };
    clinicalTrials: {
        enabled: boolean;
        maxDistance?: number;
    };
    compliance: {
        enabled: boolean;
        encryptionKey?: string;
        auditRetentionDays: number;
    };
    ml: {
        enabled: boolean;
        modelVersion: string;
    };
    safety: {
        enabled: boolean;
        strictMode: boolean;
    };
}
export interface RealWorldPatient {
    id: string;
    mrn?: string;
    demographics: {
        firstName: string;
        lastName: string;
        dateOfBirth: Date;
        gender: 'male' | 'female' | 'other';
        ethnicity?: string;
        address?: {
            city: string;
            state: string;
            zipCode: string;
            country: string;
        };
    };
    diagnosis: {
        cancerType: string;
        stage: string;
        diagnosisDate: Date;
        histology?: string;
        grade?: string;
        primarySite?: string;
        metastaticSites?: string[];
    };
    genomics?: {
        testDate?: Date;
        platform?: string;
        mutations: string[];
        biomarkers: Record<string, any>;
        msiStatus?: 'MSI-H' | 'MSS';
        tmbLevel?: 'High' | 'Low';
        tmbValue?: number;
        pdl1Expression?: number;
        hrdStatus?: boolean;
        hrdScore?: number;
    };
    treatments?: {
        treatmentId: string;
        regimen: string;
        startDate: Date;
        endDate?: Date;
        response?: 'CR' | 'PR' | 'SD' | 'PD';
        discontinuationReason?: string;
    }[];
    medications?: {
        name: string;
        dose: string;
        frequency: string;
        startDate: Date;
    }[];
    comorbidities?: string[];
    allergies?: string[];
    performanceStatus?: 0 | 1 | 2 | 3 | 4;
    labValues?: {
        testName: string;
        value: number;
        unit: string;
        date: Date;
        isAbnormal: boolean;
    }[];
}
export interface ComprehensiveTreatmentPlan {
    patientId: string;
    planId: string;
    createdAt: Date;
    createdBy: string;
    coreRecommendation: CancerCureResult;
    ehrData?: {
        source: string;
        lastSync: Date;
        patientSummary: any;
    };
    genomicData?: {
        platforms: string[];
        lastUpdated: Date;
        unifiedReport: any;
        therapyMatches: any[];
    };
    clinicalTrials?: {
        matchingTrials: {
            nctId: string;
            title: string;
            phase: string;
            eligibilityScore: number;
            distance?: number;
        }[];
        searchDate: Date;
    };
    predictions?: {
        responseProb: {
            CR: number;
            PR: number;
            SD: number;
            PD: number;
        };
        survivalEstimates: {
            pfs: {
                median: number;
                ci95: [number, number];
            };
            os: {
                median: number;
                ci95: [number, number];
            };
        };
        toxicityRisks: {
            toxicity: string;
            grade34Risk: number;
            mitigationStrategy: string;
        }[];
        resistancePrediction: {
            mechanism: string;
            probability: number;
            timeToResistance?: number;
        }[];
    };
    safetyAssessment?: {
        interactions: {
            drug1: string;
            drug2: string;
            severity: 'major' | 'moderate' | 'minor';
            description: string;
        }[];
        contraindications: {
            drug: string;
            reason: string;
            severity: 'absolute' | 'relative';
        }[];
        pharmacogenomics: {
            gene: string;
            variant: string;
            implication: string;
            recommendation: string;
        }[];
        overallSafetyScore: number;
    };
    decisionSupport?: {
        evidenceLevel: 'Category 1' | 'Category 2A' | 'Category 2B' | 'Category 3';
        guidelines: string[];
        alternativeOptions: {
            regimen: string;
            rationale: string;
            tradeoffs: string;
        }[];
        tumorBoardRequired: boolean;
    };
    patientSummary?: {
        treatmentGoal: string;
        whatToExpect: string;
        sideEffectsToWatch: string[];
        questionsForDoctor: string[];
        supportResources: string[];
    };
    compliance?: {
        consentStatus: 'obtained' | 'pending' | 'declined';
        consentDate?: Date;
        auditLogId: string;
        accessLog: {
            userId: string;
            action: string;
            timestamp: Date;
        }[];
    };
    status: 'draft' | 'pending_review' | 'approved' | 'active' | 'completed' | 'discontinued';
    approvedBy?: string;
    approvedAt?: Date;
}
export interface TreatmentOutcome {
    patientId: string;
    planId: string;
    response: {
        assessmentDate: Date;
        recistResponse: 'CR' | 'PR' | 'SD' | 'PD';
        targetLesions: {
            lesionId: string;
            baselineSize: number;
            currentSize: number;
            percentChange: number;
        }[];
        newLesions: boolean;
    };
    survival: {
        progressionDate?: Date;
        deathDate?: Date;
        lastFollowUpDate: Date;
        pfsMonths?: number;
        osMonths?: number;
    };
    toxicities: {
        toxicityType: string;
        grade: 1 | 2 | 3 | 4 | 5;
        onsetDate: Date;
        resolvedDate?: Date;
        interventionRequired: boolean;
        doseModification: 'none' | 'reduction' | 'delay' | 'discontinuation';
    }[];
    qualityOfLife: {
        assessmentDate: Date;
        instrument: 'FACT-G' | 'EORTC-QLQ-C30' | 'PRO-CTCAE' | 'other';
        totalScore: number;
        domainScores: Record<string, number>;
    }[];
    adherence: {
        overallAdherence: number;
        missedDoses: number;
        reasonsForMissing: string[];
    };
}
export declare class RealWorldOncologyService {
    private config;
    private cancerCapability;
    private ehrService;
    private genomicsService;
    private trialsService;
    private complianceService;
    private mlService;
    private safetyService;
    private validationService;
    private decisionSupportService;
    private patientPortalService;
    constructor(config?: Partial<RealWorldConfig>);
    private mergeDefaultConfig;
    /**
     * Initialize all enabled services
     */
    initialize(): Promise<void>;
    private initializeEHR;
    private initializeGenomics;
    private initializeClinicalTrials;
    private initializeCompliance;
    private initializeML;
    private initializeSafety;
    /**
     * Generate a comprehensive treatment plan for a patient
     */
    generateComprehensivePlan(patient: RealWorldPatient, clinicianId: string, options?: {
        includeTrials?: boolean;
        includePredictions?: boolean;
        includeSafetyCheck?: boolean;
        requireTumorBoard?: boolean;
    }): Promise<ComprehensiveTreatmentPlan>;
    /**
     * Record treatment outcome for validation
     */
    recordOutcome(outcome: TreatmentOutcome): Promise<void>;
    /**
     * Validate system predictions against actual outcomes
     */
    runValidation(cohortCriteria: {
        cancerTypes?: string[];
        stages?: string[];
        dateRange?: {
            start: Date;
            end: Date;
        };
        minPatients?: number;
    }): Promise<{
        cohortSize: number;
        concordanceRate: number;
        responseAUC: number;
        survivalCIndex: number;
        calibrationError: number;
        subgroupResults: Record<string, any>;
    }>;
    private logAccess;
    private fetchEHRData;
    private aggregateGenomicData;
    private findMatchingTrials;
    private generatePredictions;
    private performSafetyAssessment;
    private generateDecisionSupport;
    private createPatientSummary;
    /**
     * Convert internal patient type to CancerPatient for the capability module
     */
    private toCancerPatient;
    private calculateAge;
    /**
     * Get system status and health check
     */
    getSystemStatus(): Promise<{
        status: 'healthy' | 'degraded' | 'unhealthy';
        services: Record<string, {
            status: string;
            latency?: number;
        }>;
        lastValidation?: Date;
        modelVersion: string;
    }>;
}
export declare function createRealWorldOncologyService(config?: Partial<RealWorldConfig>): RealWorldOncologyService;
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