PopulationScreeningBatchSummaryBuilder

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of PopulationScreeningBatchSummaryBuilder for Population Screening Batch Summary Builder.

Domain limits and critical parameters

• Generates batch-level quality summary per FDA SaMD screening guidance, EU IVDR Annex I, WHO Screening Principles and MCED consortium standards: QC pass rate (≥90%) with spatial failure clustering detection, positivity rate vs expected prevalence (≤3× deviation; excess = systematic FP → BLOCK release), classifier score distribution drift (Z-score ≤2.0 vs historical baseline), triple control verification (positive/negative/NTC all must pass), index hopping rate (≤0.5%), plate position and temporal
• ⚠️ Critical: In population screening, PPV is prevalence-dependent. At 1% prevalence and 99% specificity, PPV = 50%. Every 1% specificity loss doubles FPs. Positivity >3× expected = IMMEDIATE RELEASE BLOCK. Failure clustering indicates technical, not biological, issue. Batch-level QC MUST precede individual result release. Historical baseline requires regular updating. Tool assesses COHORT-LEVEL QUALITY only; does not replace individual sample QC. Both levels required for safe screening result re

URS — User Requirements Specification

input.csv contract

BatchID,ScreeningProgram,AssayName,RunDate,TotalSamples,SamplesPassedQC,SamplesFailedQC,SamplesWithIndeterminate,QCPassRate_Percent,MinQCPassRate_Percent,ScoreDistribution_Mean,ScoreDistribution_Median,ScoreDistribution_SD,HistoricalMean_Score,HistoricalSD_Score,MaxZScore_Allowed,PositiveResults_Count,PositivityRate_Percent,ExpectedPrevalence_Percent,MaxPositivityDeviation_Fold,PositivityRate_UpperCI95,TopPredictedTissue,TopTissue_Fraction_Percent,UniqueTissues_Predicted,TissueDistribution_Anomalous,MeanCfDNA_Yield_ng,MinCfDNA_Yield_InBatch_ng,MeanCoverage_X,MeanUniformity_Percent,FailedAmplicons_Mean_Percent,PositiveControls_Total,PositiveControls_Passed,NegativeControls_Total,NegativeControls_Passed,NTCs_Total,NTCs_Clean,AllControlsPass,IndexHopping_Rate_Percent,MaxIndexHopping_Percent,PlatePositionEffect_Detected,TemporalDrift_Detected,ReagentLot,InstrumentID_Used,FailuresInSinglePlateRegion,FailureCluster_Location,FailureClustering_Detected
BATCH-MCED-2026-0142,MCED,OncoDetect_MC_v3,2026-06-08,96,94,2,1,97.9,90,0.14,0.11,0.06,0.15,0.05,2.0,2,2.1,1.5,3.0,7.4,Lung,50.0,2,false,22.5,8.0,18500,91.0,1.2,4,4,4,4,4,4,true,0.03,0.5,false,false,LOT-2026-0451,SEQ-NOVA-03,0,,false
BATCH-MCED-2026-0143,MCED,OncoDetect_MC_v3,2026-06-09,96,78,18,5,81.3,90,0.32,0.28,0.12,0.15,0.05,2.0,12,15.4,1.5,3.0,27.8,Liver,75.0,2,true,18.0,3.5,12000,78.0,8.5,4,3,4,2,4,3,false,1.8,0.5,true,true,LOT-2026-0467,SEQ-NOVA-03,14,Rows G-H Cols 9-12,true

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "populationscreeningbatchsummarybuilder",
  "utilityFolder": "PopulationScreeningBatchSummaryBuilder",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchID",
      "value": "BATCH-MCED-2026-0142",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "ScreeningProgram",
      "value": "MCED",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "AssayName",
      "value": "OncoDetect_MC_v3",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "RunDate",
      "value": "2026-06-08",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "TotalSamples",
      "value": "96",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "SamplesPassedQC",
      "value": "94",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "SamplesFailedQC",
      "value": "2",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "SamplesWithIndeterminate",
      "value": "1",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "QCPassRate_Percent",
      "value": "97.9",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "MinQCPassRate_Percent",
      "value": "90",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "ScoreDistribution_Mean",
      "value": "0.14",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "ScoreDistribution_Median",
      "value": "0.11",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-012"
    }
  ],
  "criticalFindings": [],
  "warnings": [],
  "audit": {
    "inputHash": "sha256:<calculated at runtime>",
    "rulesVersion": "<utility executable version>",
    "documentation": "PopulationScreeningBatchSummaryBuilder.documentation.html"
  }
}

Traceability matrix

IQ/OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating validator, documentation and test set.
• Retain input.csv, output.json, executable version and checksum.
• Before production use, perform IQ/OQ/PQ or equivalent CSV/CSA verification.
• Critical limits shall be verified against the approved specification, registration dossier and local SOPs.
• The utility provides structured QC decision support; final release decision remains with QA/QP and approved procedures.