/**
 * Clinical Trial Matching Engine
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  CLINICAL TRIAL MATCHING - CONNECTING PATIENTS TO NOVEL THERAPIES            ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module provides:                                                        ║
 * ║  - Biomarker-to-trial mapping                                                ║
 * ║  - Eligibility criteria assessment                                           ║
 * ║  - Trial phase and mechanism matching                                        ║
 * ║  - Geographic and logistical feasibility                                     ║
 * ║  - Basket, umbrella, and platform trial navigation                           ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */

// ═══════════════════════════════════════════════════════════════════════════════
// CLINICAL TRIAL DEFINITIONS
// ═══════════════════════════════════════════════════════════════════════════════

export interface ClinicalTrial {
  nctId: string;
  title: string;
  phase: TrialPhase;
  status: TrialStatus;
  trialType: TrialType;
  sponsor: string;
  conditions: string[];
  interventions: TrialIntervention[];
  eligibilityCriteria: EligibilityCriteria;
  locations: TrialLocation[];
  biomarkerRequirements: BiomarkerCriterion[];
  primaryEndpoint: string;
  estimatedEnrollment: number;
  studyStartDate: string;
  estimatedCompletionDate: string;
}

export type TrialPhase = 'Early Phase 1' | 'Phase 1' | 'Phase 1/2' | 'Phase 2' | 'Phase 2/3' | 'Phase 3' | 'Phase 4';
export type TrialStatus = 'Recruiting' | 'Active, not recruiting' | 'Enrolling by invitation' | 'Not yet recruiting' | 'Completed' | 'Suspended' | 'Terminated' | 'Withdrawn';
export type TrialType = 'Interventional' | 'Basket' | 'Umbrella' | 'Platform' | 'Expanded Access';

export interface TrialIntervention {
  type: 'Drug' | 'Biological' | 'Device' | 'Radiation' | 'Procedure' | 'Combination';
  name: string;
  mechanism: string;
  targetedPathway?: string;
  novelty: 'First-in-class' | 'Next-generation' | 'Combination' | 'New indication';
}

export interface EligibilityCriteria {
  ageRange: { min: number; max: number };
  gender: 'All' | 'Male' | 'Female';
  performanceStatus: { scale: 'ECOG' | 'Karnofsky'; maxValue: number };
  priorTherapyRequirements: PriorTherapyRequirement[];
  organFunctionRequirements: OrganFunctionRequirement[];
  exclusionCriteria: string[];
  inclusionCriteria: string[];
}

export interface PriorTherapyRequirement {
  requirement: 'Required' | 'Allowed' | 'Excluded';
  therapyType: string;
  details: string;
}

export interface OrganFunctionRequirement {
  organ: string;
  parameter: string;
  requirement: string;
}

export interface TrialLocation {
  facility: string;
  city: string;
  state: string;
  country: string;
  status: 'Recruiting' | 'Not yet recruiting' | 'Completed';
  contactName?: string;
  contactPhone?: string;
  contactEmail?: string;
}

export interface BiomarkerCriterion {
  biomarker: string;
  requirement: 'Required' | 'Preferred' | 'Excluded';
  testMethod: string[];
  details?: string;
}

// ═══════════════════════════════════════════════════════════════════════════════
// TRIAL MATCHING CRITERIA
// ═══════════════════════════════════════════════════════════════════════════════

export interface PatientTrialProfile {
  cancerType: string;
  histology: string;
  stage: string;
  biomarkers: PatientBiomarker[];
  priorTherapies: string[];
  currentLine: number;
  age: number;
  performanceStatus: number;
  organFunction: OrganFunctionStatus;
  location: { country: string; state?: string; city?: string };
  willingToTravel: boolean;
  maxTravelDistance?: number; // miles
  preferences: TrialPreferences;
}

export interface PatientBiomarker {
  name: string;
  status: 'Positive' | 'Negative' | 'Unknown';
  value?: string | number;
  method?: string;
}

export interface OrganFunctionStatus {
  renalFunction: 'Normal' | 'Mild impairment' | 'Moderate impairment' | 'Severe impairment';
  hepaticFunction: 'Normal' | 'Mild impairment' | 'Moderate impairment' | 'Severe impairment';
  cardiacFunction: 'Normal' | 'Reduced' | 'Severely reduced';
  bonemarrowFunction: 'Normal' | 'Reduced';
}

export interface TrialPreferences {
  preferredPhases: TrialPhase[];
  acceptPlaceboArm: boolean;
  preferLocalTrials: boolean;
  interestedMechanisms: string[];
}

export interface TrialMatch {
  trial: ClinicalTrial;
  matchScore: number;
  matchDetails: MatchDetail[];
  eligibilityStatus: 'Likely Eligible' | 'Possibly Eligible' | 'Likely Ineligible' | 'Need More Info';
  barriers: string[];
  nextSteps: string[];
}

export interface MatchDetail {
  criterion: string;
  status: 'Met' | 'Not Met' | 'Partial' | 'Unknown';
  explanation: string;
}

// ═══════════════════════════════════════════════════════════════════════════════
// TRIAL DATABASE (REPRESENTATIVE EXAMPLES)
// ═══════════════════════════════════════════════════════════════════════════════

export const TRIAL_DATABASE: ClinicalTrial[] = [
  // EGFR-mutant NSCLC Trials
  {
    nctId: 'NCT04816214',
    title: 'Amivantamab + Lazertinib vs Osimertinib in EGFR-Mutant NSCLC (MARIPOSA)',
    phase: 'Phase 3',
    status: 'Active, not recruiting',
    trialType: 'Interventional',
    sponsor: 'Janssen',
    conditions: ['NSCLC', 'EGFR-mutant'],
    interventions: [
      { type: 'Combination', name: 'Amivantamab + Lazertinib', mechanism: 'EGFR-MET bispecific + EGFR TKI', novelty: 'Combination' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Excluded', therapyType: 'Prior EGFR TKI', details: 'No prior EGFR TKI for metastatic disease' }
      ],
      organFunctionRequirements: [
        { organ: 'Renal', parameter: 'CrCl', requirement: '≥50 mL/min' },
        { organ: 'Hepatic', parameter: 'AST/ALT', requirement: '≤3x ULN' }
      ],
      exclusionCriteria: ['Active brain metastases', 'Prior EGFR TKI', 'Interstitial lung disease'],
      inclusionCriteria: ['EGFR exon 19 del or L858R', 'Metastatic NSCLC', 'Treatment-naive']
    },
    locations: [
      { facility: 'MD Anderson Cancer Center', city: 'Houston', state: 'TX', country: 'USA', status: 'Recruiting' },
      { facility: 'Memorial Sloan Kettering', city: 'New York', state: 'NY', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [
      { biomarker: 'EGFR exon 19 del or L858R', requirement: 'Required', testMethod: ['NGS', 'PCR', 'ctDNA'] }
    ],
    primaryEndpoint: 'Progression-free survival',
    estimatedEnrollment: 1074,
    studyStartDate: '2021-05',
    estimatedCompletionDate: '2025-12'
  },
  // HER2+ Breast Cancer Trials
  {
    nctId: 'NCT04784715',
    title: 'Trastuzumab Deruxtecan vs Physician Choice in HER2-low Breast Cancer (DESTINY-Breast06)',
    phase: 'Phase 3',
    status: 'Recruiting',
    trialType: 'Interventional',
    sponsor: 'Daiichi Sankyo',
    conditions: ['Breast Cancer', 'HER2-low'],
    interventions: [
      { type: 'Biological', name: 'Trastuzumab Deruxtecan', mechanism: 'HER2-directed ADC', novelty: 'New indication' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Required', therapyType: 'Prior endocrine therapy', details: 'For HR+ patients' },
        { requirement: 'Allowed', therapyType: 'Prior chemotherapy', details: '1-2 prior lines allowed' }
      ],
      organFunctionRequirements: [
        { organ: 'Cardiac', parameter: 'LVEF', requirement: '≥50%' }
      ],
      exclusionCriteria: ['HER2-positive (IHC 3+)', 'History of ILD', 'Uncontrolled brain mets'],
      inclusionCriteria: ['HER2-low (IHC 1+ or 2+/FISH-)', 'HR+ or HR-', 'Metastatic breast cancer']
    },
    locations: [
      { facility: 'Dana-Farber Cancer Institute', city: 'Boston', state: 'MA', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [
      { biomarker: 'HER2-low', requirement: 'Required', testMethod: ['IHC', 'FISH'] }
    ],
    primaryEndpoint: 'Progression-free survival',
    estimatedEnrollment: 850,
    studyStartDate: '2021-03',
    estimatedCompletionDate: '2026-06'
  },
  // KRAS G12C Trials
  {
    nctId: 'NCT04685135',
    title: 'Sotorasib + Anti-EGFR in KRAS G12C CRC (CodeBreaK 300)',
    phase: 'Phase 3',
    status: 'Recruiting',
    trialType: 'Interventional',
    sponsor: 'Amgen',
    conditions: ['Colorectal Cancer', 'KRAS G12C'],
    interventions: [
      { type: 'Combination', name: 'Sotorasib + Panitumumab', mechanism: 'KRAS G12C inhibitor + anti-EGFR', novelty: 'Combination' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Required', therapyType: 'Prior chemotherapy', details: '1-2 prior lines for metastatic disease' }
      ],
      organFunctionRequirements: [],
      exclusionCriteria: ['Prior KRAS G12C inhibitor', 'Symptomatic brain mets'],
      inclusionCriteria: ['KRAS G12C mutation', 'Metastatic CRC', 'Prior fluoropyrimidine, oxaliplatin, irinotecan']
    },
    locations: [
      { facility: 'Multiple sites', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [
      { biomarker: 'KRAS G12C', requirement: 'Required', testMethod: ['NGS', 'PCR'] }
    ],
    primaryEndpoint: 'Overall survival',
    estimatedEnrollment: 160,
    studyStartDate: '2021-01',
    estimatedCompletionDate: '2025-06'
  },
  // Basket Trial Example
  {
    nctId: 'NCT02465060',
    title: 'NCI-MATCH: Targeted Therapy Directed by Genetic Testing (Basket Trial)',
    phase: 'Phase 2',
    status: 'Active, not recruiting',
    trialType: 'Basket',
    sponsor: 'NCI',
    conditions: ['Solid Tumors', 'Lymphoma'],
    interventions: [
      { type: 'Drug', name: 'Multiple targeted agents', mechanism: 'Various - based on molecular alteration', novelty: 'First-in-class' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Required', therapyType: 'Prior standard therapy', details: 'Progressed on standard options' }
      ],
      organFunctionRequirements: [],
      exclusionCriteria: ['Matched targeted therapy previously received'],
      inclusionCriteria: ['Actionable genomic alteration', 'No standard treatment options']
    },
    locations: [
      { facility: 'ECOG-ACRIN Network Sites', city: 'Multiple', state: 'Multiple', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [
      { biomarker: 'Actionable mutation per NCI-MATCH arms', requirement: 'Required', testMethod: ['NGS'] }
    ],
    primaryEndpoint: 'Overall response rate',
    estimatedEnrollment: 6000,
    studyStartDate: '2015-08',
    estimatedCompletionDate: '2025-12'
  },
  // Immunotherapy Combination
  {
    nctId: 'NCT03899610',
    title: 'Nivolumab + Relatlimab vs Nivolumab in Melanoma (RELATIVITY-047)',
    phase: 'Phase 3',
    status: 'Active, not recruiting',
    trialType: 'Interventional',
    sponsor: 'Bristol-Myers Squibb',
    conditions: ['Melanoma'],
    interventions: [
      { type: 'Combination', name: 'Nivolumab + Relatlimab', mechanism: 'Anti-PD-1 + Anti-LAG-3', novelty: 'First-in-class' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Excluded', therapyType: 'Prior anti-PD-1/PD-L1', details: 'No prior checkpoint inhibitor' }
      ],
      organFunctionRequirements: [],
      exclusionCriteria: ['Active autoimmune disease', 'Prior immunotherapy'],
      inclusionCriteria: ['Unresectable or metastatic melanoma', 'Treatment-naive for metastatic disease']
    },
    locations: [
      { facility: 'Multiple sites', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [],
    primaryEndpoint: 'Progression-free survival',
    estimatedEnrollment: 714,
    studyStartDate: '2019-04',
    estimatedCompletionDate: '2024-12'
  },
  // CAR-T Trial
  {
    nctId: 'NCT04503278',
    title: 'Cilta-cel vs Standard of Care in Multiple Myeloma (CARTITUDE-4)',
    phase: 'Phase 3',
    status: 'Active, not recruiting',
    trialType: 'Interventional',
    sponsor: 'Janssen',
    conditions: ['Multiple Myeloma'],
    interventions: [
      { type: 'Biological', name: 'Ciltacabtagene autoleucel (Cilta-cel)', mechanism: 'BCMA-directed CAR-T', novelty: 'Next-generation' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 18, max: 99 },
      gender: 'All',
      performanceStatus: { scale: 'ECOG', maxValue: 1 },
      priorTherapyRequirements: [
        { requirement: 'Required', therapyType: 'Prior lenalidomide and PI', details: '1-3 prior lines including lenalidomide and a PI' }
      ],
      organFunctionRequirements: [
        { organ: 'Cardiac', parameter: 'LVEF', requirement: '≥45%' },
        { organ: 'Pulmonary', parameter: 'O2 sat', requirement: '≥92% on room air' }
      ],
      exclusionCriteria: ['Prior BCMA-targeted therapy', 'Active CNS involvement', 'Uncontrolled infection'],
      inclusionCriteria: ['Relapsed/refractory MM', 'Lenalidomide-refractory', '1-3 prior lines']
    },
    locations: [
      { facility: 'Multiple academic centers', city: 'Various', state: 'Various', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [],
    primaryEndpoint: 'Progression-free survival',
    estimatedEnrollment: 400,
    studyStartDate: '2020-06',
    estimatedCompletionDate: '2026-01'
  },
  // Pediatric Trial
  {
    nctId: 'NCT03155620',
    title: 'Larotrectinib in Pediatric Solid Tumors with NTRK Fusion (SCOUT)',
    phase: 'Phase 1/2',
    status: 'Recruiting',
    trialType: 'Basket',
    sponsor: 'Bayer',
    conditions: ['Pediatric Solid Tumors', 'NTRK Fusion'],
    interventions: [
      { type: 'Drug', name: 'Larotrectinib', mechanism: 'TRK inhibitor', novelty: 'First-in-class' }
    ],
    eligibilityCriteria: {
      ageRange: { min: 0, max: 21 },
      gender: 'All',
      performanceStatus: { scale: 'Karnofsky', maxValue: 50 },
      priorTherapyRequirements: [
        { requirement: 'Allowed', therapyType: 'Prior therapy', details: 'No limit on prior therapies' }
      ],
      organFunctionRequirements: [],
      exclusionCriteria: ['Prior TRK inhibitor', 'Primary CNS tumor'],
      inclusionCriteria: ['NTRK gene fusion', 'Relapsed or refractory solid tumor', 'Age ≤21']
    },
    locations: [
      { facility: "Children's Hospital of Philadelphia", city: 'Philadelphia', state: 'PA', country: 'USA', status: 'Recruiting' },
      { facility: 'Texas Childrens Hospital', city: 'Houston', state: 'TX', country: 'USA', status: 'Recruiting' }
    ],
    biomarkerRequirements: [
      { biomarker: 'NTRK1/2/3 fusion', requirement: 'Required', testMethod: ['NGS', 'FISH', 'IHC'] }
    ],
    primaryEndpoint: 'Overall response rate',
    estimatedEnrollment: 150,
    studyStartDate: '2017-07',
    estimatedCompletionDate: '2025-12'
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// TRIAL MATCHING ENGINE
// ═══════════════════════════════════════════════════════════════════════════════

export class ClinicalTrialMatchingEngine {
  private trials: ClinicalTrial[] = TRIAL_DATABASE;

  findMatchingTrials(patient: PatientTrialProfile): TrialMatch[] {
    const matches: TrialMatch[] = [];

    for (const trial of this.trials) {
      if (trial.status === 'Withdrawn' || trial.status === 'Terminated') continue;

      const matchResult = this.evaluateTrialMatch(patient, trial);
      if (matchResult.matchScore > 0) {
        matches.push(matchResult);
      }
    }

    return matches.sort((a, b) => b.matchScore - a.matchScore);
  }

  private evaluateTrialMatch(patient: PatientTrialProfile, trial: ClinicalTrial): TrialMatch {
    const matchDetails: MatchDetail[] = [];
    const barriers: string[] = [];
    let score = 0;

    // Check cancer type match
    const cancerMatch = trial.conditions.some(c =>
      c.toLowerCase().includes(patient.cancerType.toLowerCase()) ||
      patient.cancerType.toLowerCase().includes(c.toLowerCase())
    );
    if (cancerMatch) {
      score += 30;
      matchDetails.push({ criterion: 'Cancer type', status: 'Met', explanation: 'Cancer type matches trial conditions' });
    } else {
      matchDetails.push({ criterion: 'Cancer type', status: 'Not Met', explanation: 'Cancer type does not match' });
    }

    // Check biomarker requirements
    for (const bioReq of trial.biomarkerRequirements) {
      const patientBiomarker = patient.biomarkers.find(b =>
        b.name.toLowerCase().includes(bioReq.biomarker.toLowerCase()) ||
        bioReq.biomarker.toLowerCase().includes(b.name.toLowerCase())
      );

      if (bioReq.requirement === 'Required') {
        if (patientBiomarker?.status === 'Positive') {
          score += 25;
          matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Met', explanation: 'Required biomarker is positive' });
        } else if (patientBiomarker?.status === 'Negative') {
          score -= 50;
          barriers.push(`Required biomarker ${bioReq.biomarker} is negative`);
          matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Not Met', explanation: 'Required biomarker is negative' });
        } else {
          matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Unknown', explanation: 'Biomarker status not tested' });
        }
      } else if (bioReq.requirement === 'Excluded') {
        if (patientBiomarker?.status === 'Positive') {
          score -= 50;
          barriers.push(`Excluded biomarker ${bioReq.biomarker} is positive`);
          matchDetails.push({ criterion: `Biomarker: ${bioReq.biomarker}`, status: 'Not Met', explanation: 'Excluded biomarker is positive' });
        }
      }
    }

    // Check age eligibility
    const ageElig = trial.eligibilityCriteria.ageRange;
    if (patient.age >= ageElig.min && patient.age <= ageElig.max) {
      score += 10;
      matchDetails.push({ criterion: 'Age', status: 'Met', explanation: `Age ${patient.age} within range ${ageElig.min}-${ageElig.max}` });
    } else {
      barriers.push(`Age ${patient.age} outside eligible range ${ageElig.min}-${ageElig.max}`);
      matchDetails.push({ criterion: 'Age', status: 'Not Met', explanation: 'Age outside eligible range' });
    }

    // Check performance status
    const psReq = trial.eligibilityCriteria.performanceStatus;
    if (patient.performanceStatus <= psReq.maxValue) {
      score += 10;
      matchDetails.push({ criterion: 'Performance status', status: 'Met', explanation: `PS ${patient.performanceStatus} meets requirement ≤${psReq.maxValue}` });
    } else {
      barriers.push(`Performance status ${patient.performanceStatus} exceeds maximum ${psReq.maxValue}`);
      matchDetails.push({ criterion: 'Performance status', status: 'Not Met', explanation: 'Performance status too high' });
    }

    // Check phase preference
    if (patient.preferences.preferredPhases.includes(trial.phase)) {
      score += 5;
    }

    // Check location
    const matchingLocation = trial.locations.find(loc =>
      loc.country === patient.location.country &&
      loc.status === 'Recruiting'
    );
    if (matchingLocation) {
      score += 10;
      matchDetails.push({ criterion: 'Location', status: 'Met', explanation: `Trial available in ${matchingLocation.city}, ${matchingLocation.state}` });
    } else if (patient.willingToTravel) {
      score += 5;
      matchDetails.push({ criterion: 'Location', status: 'Partial', explanation: 'Patient willing to travel' });
    } else {
      barriers.push('No recruiting sites in patient location');
      matchDetails.push({ criterion: 'Location', status: 'Not Met', explanation: 'No local sites; travel required' });
    }

    // Determine eligibility status
    let eligibilityStatus: TrialMatch['eligibilityStatus'];
    if (barriers.length === 0 && score > 50) {
      eligibilityStatus = 'Likely Eligible';
    } else if (barriers.length === 0) {
      eligibilityStatus = 'Need More Info';
    } else if (barriers.some(b => b.includes('Required biomarker') || b.includes('Age'))) {
      eligibilityStatus = 'Likely Ineligible';
    } else {
      eligibilityStatus = 'Possibly Eligible';
    }

    // Generate next steps
    const nextSteps: string[] = [];
    if (eligibilityStatus === 'Likely Eligible' || eligibilityStatus === 'Possibly Eligible') {
      nextSteps.push('Discuss with oncologist');
      nextSteps.push(`Contact trial site: ${trial.locations[0]?.facility || 'See ClinicalTrials.gov'}`);
      nextSteps.push(`Search ClinicalTrials.gov for NCT: ${trial.nctId}`);
    }
    if (matchDetails.some(m => m.status === 'Unknown')) {
      nextSteps.push('Complete biomarker testing');
    }

    return {
      trial,
      matchScore: Math.max(0, score),
      matchDetails,
      eligibilityStatus,
      barriers,
      nextSteps
    };
  }

  findTrialsByBiomarker(biomarker: string): ClinicalTrial[] {
    return this.trials.filter(trial =>
      trial.biomarkerRequirements.some(b =>
        b.biomarker.toLowerCase().includes(biomarker.toLowerCase())
      )
    );
  }

  findTrialsByMechanism(mechanism: string): ClinicalTrial[] {
    return this.trials.filter(trial =>
      trial.interventions.some(i =>
        i.mechanism.toLowerCase().includes(mechanism.toLowerCase())
      )
    );
  }

  findBasketTrials(): ClinicalTrial[] {
    return this.trials.filter(trial => trial.trialType === 'Basket');
  }

  findPediatricTrials(): ClinicalTrial[] {
    return this.trials.filter(trial =>
      trial.eligibilityCriteria.ageRange.min < 18 ||
      trial.conditions.some(c => c.toLowerCase().includes('pediatric'))
    );
  }

  getTrialById(nctId: string): ClinicalTrial | undefined {
    return this.trials.find(t => t.nctId === nctId);
  }

  generateTrialSearchStrategy(patient: PatientTrialProfile): {
    searchTerms: string[];
    recommendedDatabases: string[];
    searchTips: string[];
  } {
    const searchTerms: string[] = [
      patient.cancerType,
      patient.histology,
      ...patient.biomarkers.filter(b => b.status === 'Positive').map(b => b.name)
    ];

    return {
      searchTerms,
      recommendedDatabases: [
        'ClinicalTrials.gov (clinicaltrials.gov)',
        'NCI Cancer Clinical Trials (cancer.gov/clinicaltrials)',
        'TrialMatch (lls.org/support/information-specialists)',
        'EmergingMed Navigator (emergingmed.com)'
      ],
      searchTips: [
        'Use condition + biomarker for targeted searches',
        'Filter by "Recruiting" status',
        'Check Phase 1/2 trials for novel mechanisms',
        'Consider basket trials if you have an actionable mutation',
        'Contact trial coordinators directly for eligibility questions'
      ]
    };
  }
}

// Export singleton
export const clinicalTrialMatchingEngine = new ClinicalTrialMatchingEngine();