/**
 * ClinicalTrials.gov Integration
 *
 * Provides real-time access to clinical trial data from ClinicalTrials.gov
 * using the official API v2. Enables matching patients to eligible trials
 * based on their cancer type, biomarkers, and treatment history.
 */
import { EventEmitter } from 'events';
export interface ClinicalTrial {
    nctId: string;
    title: string;
    briefTitle?: string;
    officialTitle?: string;
    status: TrialStatus;
    phase: TrialPhase;
    studyType: 'interventional' | 'observational' | 'expanded-access';
    conditions: string[];
    interventions: TrialIntervention[];
    eligibility: TrialEligibility;
    locations: TrialLocation[];
    sponsors: TrialSponsor[];
    contacts: TrialContact[];
    dates: {
        startDate?: Date;
        primaryCompletionDate?: Date;
        completionDate?: Date;
        firstPostedDate?: Date;
        lastUpdatePostedDate?: Date;
    };
    enrollment?: {
        count: number;
        type: 'actual' | 'anticipated';
    };
    arms?: TrialArm[];
    outcomes?: TrialOutcome[];
    biomarkerRequirements?: BiomarkerRequirement[];
    references?: string[];
    url: string;
}
export type TrialStatus = 'not-yet-recruiting' | 'recruiting' | 'enrolling-by-invitation' | 'active-not-recruiting' | 'suspended' | 'terminated' | 'completed' | 'withdrawn' | 'unknown';
export type TrialPhase = 'early-phase-1' | 'phase-1' | 'phase-1-2' | 'phase-2' | 'phase-2-3' | 'phase-3' | 'phase-4' | 'not-applicable';
export interface TrialIntervention {
    type: 'drug' | 'biological' | 'device' | 'procedure' | 'radiation' | 'behavioral' | 'genetic' | 'dietary' | 'combination' | 'other';
    name: string;
    description?: string;
    armGroupLabels?: string[];
    otherNames?: string[];
}
export interface TrialEligibility {
    criteria: string;
    gender: 'all' | 'female' | 'male';
    minimumAge?: string;
    maximumAge?: string;
    healthyVolunteers: boolean;
    inclusionCriteria?: string[];
    exclusionCriteria?: string[];
}
export interface TrialLocation {
    facility: string;
    city: string;
    state?: string;
    country: string;
    zip?: string;
    status?: 'recruiting' | 'not-recruiting' | 'withdrawn' | 'active' | 'completed';
    contact?: {
        name?: string;
        phone?: string;
        email?: string;
    };
    coordinates?: {
        latitude: number;
        longitude: number;
    };
    distance?: number;
}
export interface TrialSponsor {
    name: string;
    type: 'principal-investigator' | 'sponsor' | 'sponsor-investigator';
    leadOrCollaborator: 'lead' | 'collaborator';
}
export interface TrialContact {
    name?: string;
    phone?: string;
    email?: string;
    role?: string;
}
export interface TrialArm {
    label: string;
    type: 'experimental' | 'active-comparator' | 'placebo-comparator' | 'sham-comparator' | 'no-intervention' | 'other';
    description?: string;
    interventions?: string[];
}
export interface TrialOutcome {
    type: 'primary' | 'secondary' | 'other';
    measure: string;
    description?: string;
    timeFrame?: string;
}
export interface BiomarkerRequirement {
    biomarker: string;
    requirement: 'required' | 'excluded' | 'preferred';
    value?: string;
    operator?: 'equals' | 'greater-than' | 'less-than' | 'between';
}
export interface TrialSearchParams {
    condition?: string;
    conditionTerms?: string[];
    intervention?: string;
    interventionType?: TrialIntervention['type'];
    drugName?: string;
    biomarkers?: string[];
    genomicAlterations?: string[];
    status?: TrialStatus[];
    phase?: TrialPhase[];
    country?: string;
    state?: string;
    city?: string;
    zipCode?: string;
    distance?: number;
    coordinates?: {
        lat: number;
        lon: number;
    };
    age?: number;
    gender?: 'male' | 'female';
    sponsorType?: 'industry' | 'academic' | 'government' | 'other';
    funderType?: 'nih' | 'industry' | 'other';
    studyType?: 'interventional' | 'observational' | 'expanded-access';
    hasResults?: boolean;
    pageSize?: number;
    pageToken?: string;
}
export interface TrialSearchResult {
    trials: ClinicalTrial[];
    totalCount: number;
    nextPageToken?: string;
}
export interface PatientProfile {
    cancerType: string;
    stage?: string;
    age?: number;
    gender?: 'male' | 'female';
    ecogStatus?: number;
    biomarkers?: {
        name: string;
        value: string | number;
        status?: 'positive' | 'negative';
    }[];
    genomicAlterations?: {
        gene: string;
        alteration: string;
        type: 'mutation' | 'fusion' | 'amplification' | 'deletion';
    }[];
    msiStatus?: 'MSI-H' | 'MSI-L' | 'MSS';
    tmbLevel?: 'high' | 'low';
    pdl1Score?: number;
    hrdStatus?: 'positive' | 'negative';
    priorTherapies?: string[];
    comorbidities?: string[];
    location?: {
        zipCode?: string;
        city?: string;
        state?: string;
        country?: string;
        coordinates?: {
            lat: number;
            lon: number;
        };
    };
    maxTravelDistance?: number;
}
export interface TrialMatch {
    trial: ClinicalTrial;
    matchScore: number;
    matchReasons: string[];
    eligibilityAssessment: {
        status: 'likely-eligible' | 'possibly-eligible' | 'likely-ineligible' | 'unknown';
        matchingCriteria: string[];
        potentialExclusions: string[];
        missingInformation: string[];
    };
    nearestLocation?: TrialLocation;
    biomarkerMatches?: {
        biomarker: string;
        trialRequirement: string;
        patientValue: string;
        match: boolean;
    }[];
}
export declare class ClinicalTrialsGovClient extends EventEmitter {
    private baseUrl;
    private timeout;
    private cache;
    private cacheDuration;
    constructor(options?: {
        timeout?: number;
        cacheDuration?: number;
    });
    /**
     * Search for clinical trials
     */
    searchTrials(params: TrialSearchParams): Promise<TrialSearchResult>;
    /**
     * Get a specific trial by NCT ID
     */
    getTrial(nctId: string): Promise<ClinicalTrial>;
    /**
     * Get multiple trials by NCT IDs
     */
    getTrials(nctIds: string[]): Promise<ClinicalTrial[]>;
    /**
     * Search for trials matching a patient profile
     */
    findMatchingTrials(patient: PatientProfile): Promise<TrialMatch[]>;
    /**
     * Search for trials by biomarker
     */
    searchByBiomarker(biomarker: string, options?: {
        cancerType?: string;
        status?: TrialStatus[];
        phase?: TrialPhase[];
    }): Promise<ClinicalTrial[]>;
    /**
     * Search for trials by drug/intervention
     */
    searchByDrug(drugName: string, options?: {
        cancerType?: string;
        status?: TrialStatus[];
        phase?: TrialPhase[];
    }): Promise<ClinicalTrial[]>;
    /**
     * Get trials for a specific cancer type
     */
    getTrialsForCancerType(cancerType: string, options?: {
        phase?: TrialPhase[];
        location?: {
            country?: string;
            state?: string;
        };
        biomarkers?: string[];
    }): Promise<ClinicalTrial[]>;
    private buildSearchQuery;
    private mapStudyToTrial;
    private mapTrialStatus;
    private mapTrialPhase;
    private mapStudyType;
    private mapInterventionType;
    private mapLocationStatus;
    private mapArmType;
    private mapGender;
    private parseEligibilityCriteria;
    private extractBiomarkerRequirements;
    private assessTrialMatch;
    private calculateDistance;
    private toRadians;
    private httpRequest;
    private getFromCache;
    private setCache;
    /**
     * Clear the cache
     */
    clearCache(): void;
}
export default ClinicalTrialsGovClient;
//# sourceMappingURL=clinicalTrialsGov.d.ts.map