FalsePositiveReviewWorkflowBuilder

False Positive Review Workflow Builder

Liquid Biopsy жидкостная биопсия cfDNA ctDNA CTC exosomes NGS qPCR

Utility description: False Positive Review Workflow Builder

False Positive Review Workflow Builder — FP Review Workflow Construction

ℹ️ Utility constructs and validates structured expert review workflow for false-positive results according to CAP/CLIA, FDA SaMD and GMLP:
• Trigger Criteria: Clear conditions for automatic review initiation (VAF, variant novelty, discordance).
• Multi-Tier Review: Sequential technical, bioinformatic, and biological level verification.
• Orthogonal Confirmation: Mandatory confirmation by alternative method (ddPCR, Sanger, IHC).
• Escalation Path: Mechanism for resolving disagreements and complex cases.
• Approval Status: Control of workflow approval by authorized person.

⚠️ IMPORTANT:
• False-positive result in oncology may lead to unnecessary toxic therapy.
• Workflow without orthogonal confirmation does not reduce FP risk to acceptable level.
• Unapproved workflow has no legal standing in clinical practice.

Usage:
FalsePositiveReviewWorkflowBuilder.exe → demo mode (console output)
FalsePositiveReviewWorkflowBuilder.exe input.csv output.json → evaluate your data

Input format:
WorkflowID,AssayType,TriggerCriteria,HasTechnicalCheck,HasBioinformaticCheck,HasBiologicalPlausibilityCheck,HasOrthogonalConfirmation,HasEscalationPath,HasConclusionTemplate,HasTurnaroundTime,MaxTurnaroundHours,ResponsibleRole_Technical,ResponsibleRole_Bioinformatic,ResponsibleRole_Clinical,WorkflowApproved,ApprovalDate

Example:
FP-WF-001,NGS_Panel,VAF<5% OR novel,true,true,true,true,true,true,true,48,Technologist,Bioinformatician,Pathologist,true,2026-01-15

📍 Scope of Application (Usage Where):
• Clinical NGS Laboratories: Standardization of suspicious variant review.
• SaMD Developers: Documentation of risk mitigation strategy for AI/ML classifiers.
• CAP Accreditation: Demonstration of result quality management system.
• Multidisciplinary Tumor Boards: Formalization of decision-making process.

— WHY IS THIS NEEDED?
Automated pipelines generate false positives at 1-10% frequency.
Without formalized review, these errors reach physicians and influence treatment.
Structured workflow transforms subjective "I think this is an artifact" into objective, reproducible, auditable process.
This is critically important for patient safety and regulatory compliance.

⚠️ CRITICAL:
• Trigger Criteria: Must be quantitative and unambiguous.
• Orthogonal Confirmation: MANDATORY for all FP-suspect results.
• Escalation Path: Must include medical director or external expert level.
• TAT: Must account for clinical urgency (oncology ≤48-72h).
• Approval: Only approved workflow may be used for clinical decisions.

Key features:
• Eight-parameter workflow completeness check
• Adaptation per test type (NGS, ddPCR, LB, MCED)
• Critical and major gap identification
• Regulatory-ready JSON generation
• Compliance with CAP, FDA SaMD, GMLP

Critical parameters:
• Trigger Criteria: Defined
• Technical Check: Present
• Biological Plausibility: Present
• Orthogonal Confirmation: Present
• Escalation Path: Defined
• Workflow Approved: True

💡 Usage tips:
1. Triggers: Customize per test specificity (VAF for NGS, droplet count for ddPCR).
2. Orthogonality: Pre-define available confirmation methods for each variant type.
3. Roles: Clearly assign responsibility; avoid role ambiguity.
4. Templates: Use standardized conclusion wording ("Confirmed FP", "True Positive", "Indeterminate").
5. Revision: Update workflow upon pipeline changes, new artifact emergence, or regulatory requirement updates.

⚠️ Note: This utility verifies workflow STRUCTURE, not its clinical effectiveness. Effectiveness must be confirmed by retrospective FP-rate analysis before and after workflow implementation.

input.csv

WorkflowID,AssayType,TriggerCriteria,HasTechnicalCheck,HasBioinformaticCheck,HasBiologicalPlausibilityCheck,HasOrthogonalConfirmation,HasEscalationPath,HasConclusionTemplate,HasTurnaroundTime,MaxTurnaroundHours,ResponsibleRole_Technical,ResponsibleRole_Bioinformatic,ResponsibleRole_Clinical,WorkflowApproved,ApprovalDate
FP-WF-NGS-001,NGS_Panel,VAF < 5% OR novel variant OR discordant with phenotype,true,true,true,true,true,true,true,48,Lab Technologist,Bioinformatician,Molecular Pathologist,true,2026-01-15
FP-WF-DDPCR-002,ddPCR,Positive droplets < 10 OR NTC contamination,true,false,true,false,false,true,true,24,Lab Technologist,,Molecular Pathologist,false,
FP-WF-LB-003,LiquidBiopsy,ctDNA VAF < 0.5% OR unexpected tissue origin,true,true,true,true,true,true,true,72,Lab Technologist,Bioinformatician,Oncologist,true,2026-03-01

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of FalsePositiveReviewWorkflowBuilder for False Positive Review Workflow Builder.

Domain limits URS input.csv FS IQ/OQ/PQ

Domain limits and critical parameters

Key fragments from the source description are shown below. Before production use, limits must be verified against the approved specification, registration dossier and local SOPs.

FP-WF-001,NGS_Panel,VAF<5% OR novel,true,true,true,true,true,true,true,48,Technologist,Bioinformatician,Pathologist,true,2026-01-15
• Clinical NGS Laboratories: Standardization of suspicious variant review.
This is critically important for patient safety and regulatory compliance.
⚠️ CRITICAL:
• Trigger Criteria: Must be quantitative and unambiguous.
• Orthogonal Confirmation: MANDATORY for all FP-suspect results.
• Escalation Path: Must include medical director or external expert level.
• TAT: Must account for clinical urgency (oncology ≤48-72h).
• Critical and major gap identification
Critical parameters:
⚠️ Note: This utility verifies workflow STRUCTURE, not its clinical effectiveness. Effectiveness must be confirmed by retrospective FP-rate analysis before and after workflow implementation.

URS — User Requirements Specification

ID	Requirement	Criticality	Acceptance criterion
URS-001	The utility shall accept an input.csv file for False Positive Review Workflow Builder with headers defined in the data contract.	High	The file is processed without manual header editing.
URS-002	The utility shall perform deterministic QC evaluation without machine learning and without probabilistic conformance decisions.	High	Identical input data, rule version and configuration produce reproducible results.
URS-003	The utility shall validate mandatory fields, data types, ranges, units and domain plausibility.	High	Schema, conversion and range errors are explicitly reported.
URS-004	The utility shall apply domain limits and rules from the description, approved specification, registration dossier and local SOPs.	High	Each check has PASS/WARNING/FAIL and a clear message.
URS-005	The utility shall generate output.json with machine-readable results, source values, warnings, failures and critical findings.	High	JSON is suitable for LIMS/ELN/MES integration and QA/QC review.
URS-006	The utility shall preserve traceability between batch/sample, input file, applied rules and final status.	High	Output contains identifiers, checked parameters and audit metadata.
URS-007	The documentation shall support IQ/OQ/PQ, CSV/CSA and review by internal QA or inspectors.	Medium	URS, FS, input/output contract and test scenarios are supplied with the utility.
URS-008	The utility shall be used as a QC decision-support tool and not as a substitute for approved specifications and QA/QP release decision.	Medium	Documentation states change control and limit-verification expectations.

input.csv contract

#	Field	Type	Sample	Purpose
1	`WorkflowID`	string / controlled vocabulary	`FP-WF-NGS-001`	Controlled input parameter for deterministic QC rules.
2	`AssayType`	string / controlled vocabulary	`NGS_Panel`	Controlled input parameter for deterministic QC rules.
3	`TriggerCriteria`	string / controlled vocabulary	`VAF < 5% OR novel variant OR discordant with phenotype`	Controlled input parameter for deterministic QC rules.
4	`HasTechnicalCheck`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
5	`HasBioinformaticCheck`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
6	`HasBiologicalPlausibilityCheck`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
7	`HasOrthogonalConfirmation`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
8	`HasEscalationPath`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
9	`HasConclusionTemplate`	string / controlled vocabulary	`true`	Temperature profile/MKT; storage, shipping and stability parameter.
10	`HasTurnaroundTime`	string / controlled vocabulary	`true`	Time parameter for process, incubation, storage or analytical workflow.
11	`MaxTurnaroundHours`	integer / decimal	`48`	Time parameter for process, incubation, storage or analytical workflow.
12	`ResponsibleRole_Technical`	string / controlled vocabulary	`Lab Technologist`	Controlled input parameter for deterministic QC rules.
13	`ResponsibleRole_Bioinformatic`	string / controlled vocabulary	`Bioinformatician`	Controlled input parameter for deterministic QC rules.
14	`ResponsibleRole_Clinical`	string / controlled vocabulary	`Molecular Pathologist`	Controlled input parameter for deterministic QC rules.
15	`WorkflowApproved`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
16	`ApprovalDate`	string / controlled vocabulary	`2026-01-15`	Controlled input parameter for deterministic QC rules.

WorkflowID,AssayType,TriggerCriteria,HasTechnicalCheck,HasBioinformaticCheck,HasBiologicalPlausibilityCheck,HasOrthogonalConfirmation,HasEscalationPath,HasConclusionTemplate,HasTurnaroundTime,MaxTurnaroundHours,ResponsibleRole_Technical,ResponsibleRole_Bioinformatic,ResponsibleRole_Clinical,WorkflowApproved,ApprovalDate
FP-WF-NGS-001,NGS_Panel,VAF < 5% OR novel variant OR discordant with phenotype,true,true,true,true,true,true,true,48,Lab Technologist,Bioinformatician,Molecular Pathologist,true,2026-01-15
FP-WF-DDPCR-002,ddPCR,Positive droplets < 10 OR NTC contamination,true,false,true,false,false,true,true,24,Lab Technologist,,Molecular Pathologist,false,
FP-WF-LB-003,LiquidBiopsy,ctDNA VAF < 0.5% OR unexpected tissue origin,true,true,true,true,true,true,true,72,Lab Technologist,Bioinformatician,Oncologist,true,2026-03-01

Input validation rules

ID	Field	Rule	Criticality
VR-001	`WorkflowID`	The field shall match an approved dictionary or accepted string representation.	High
VR-002	`AssayType`	The field shall match an approved dictionary or accepted string representation.	High
VR-003	`TriggerCriteria`	The field shall match an approved dictionary or accepted string representation.	High
VR-004	`HasTechnicalCheck`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-005	`HasBioinformaticCheck`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-006	`HasBiologicalPlausibilityCheck`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-007	`HasOrthogonalConfirmation`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-008	`HasEscalationPath`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-009	`HasConclusionTemplate`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-010	`HasTurnaroundTime`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-011	`MaxTurnaroundHours`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-012	`ResponsibleRole_Technical`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-013	`ResponsibleRole_Bioinformatic`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-014	`ResponsibleRole_Clinical`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-015	`WorkflowApproved`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-016	`ApprovalDate`	The field shall match an approved dictionary or accepted string representation.	Medium

FS — Functional Specification

ID	Function	Implementation
FS-001	CLI execution	Support execution modes: demo mode without arguments and production mode input.csv output.json.
FS-002	CSV import	Read input.csv in UTF-8/CSV-compatible format and validate header and expected columns.
FS-003	Schema validation	Check mandatory fields, column count, unknown key fields and empty mandatory values.
FS-004	Type conversion	Convert numeric, flag and text values; invalid format is recorded as a row-level error.
FS-005	Domain rule engine	Apply rules for False Positive Review Workflow Builder, including critical limits from the description and approved specification.
FS-006	Status aggregation	Produce final status: FAIL for critical failure, WARNING for non-critical deviation, PASS for conformance.
FS-007	JSON export	Write output.json with detailed checks, source values, warnings, failures and critical findings.
FS-008	Audit support	Keep result structure suitable for review, deviation investigation and calculation reproduction.
FS-009	Integration contract	Support the scenario LIMS/ELN/MES → input.csv → utility → output.json → portal/admin review.
FS-010	Error handling	Return explicit messages for missing file, empty CSV, invalid schema, output write failure and invalid format.

Example output.json

{
  "utilityId": "falsepositivereviewworkflowbuilder",
  "utilityFolder": "FalsePositiveReviewWorkflowBuilder",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "WorkflowID",
      "value": "FP-WF-NGS-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "AssayType",
      "value": "NGS_Panel",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "TriggerCriteria",
      "value": "VAF < 5% OR novel variant OR discordant with phenotype",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "HasTechnicalCheck",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "HasBioinformaticCheck",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "HasBiologicalPlausibilityCheck",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "HasOrthogonalConfirmation",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "HasEscalationPath",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "HasConclusionTemplate",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "HasTurnaroundTime",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "MaxTurnaroundHours",
      "value": "48",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "ResponsibleRole_Technical",
      "value": "Lab Technologist",
      "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": "FalsePositiveReviewWorkflowBuilder.documentation.html"
  }
}

Traceability matrix

URS	FS	Test	Evidence
URS-001	FS-001, FS-002	OQ-001	Verify execution and import of valid input.csv.
URS-002	FS-005, FS-006	OQ-004	Repeat the same dataset and compare output.json.
URS-003	FS-003, FS-004, FS-010	OQ-002, OQ-003	Verify missing columns and invalid types.
URS-004	FS-005, FS-006	OQ-004, PQ-001	Verify critical deviations on real/boundary data.
URS-005	FS-007, FS-009	OQ-005	Verify JSON schema and downstream-system suitability.
URS-006	FS-008	OQ-006	Verify identifiers and audit metadata.
URS-007	FS-008, FS-010	IQ-001, OQ-007	Verify documentation completeness and control evidence.
URS-008	FS-005, FS-008	PQ-002	Verify review workflow and no replacement of QA decision.

IQ/OQ/PQ test scenarios

ID	Scenario	Expected result
IQ-001	Verify executable, input.csv, documentation and checksum availability.	Delivery set is complete; version is recorded.
OQ-001	Valid sample row from input.csv.	PASS or acceptable WARNING according to rules.
OQ-002	Remove a mandatory CSV column.	Schema error or FAIL with missing-column reference.
OQ-003	Place a non-numeric value into a numeric field.	Type-conversion error with row/field reference.
OQ-004	Set a critical parameter outside the limit.	FAIL and critical finding.
OQ-005	Verify output.json structure.	All mandatory sections are present and JSON is valid.
OQ-006	Verify batch/sample traceability.	Input and result identifiers match.
PQ-001	Verify 3–5 real user batches/samples.	Result is confirmed by QC/QA review.
PQ-002	Verify deviation workflow and manual QA decision.	Utility supports review but does not replace approved decision.

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.

Included in packages

Liquid Biopsy QC Suite

QC and pre-analytical control package for liquid biopsy workflows: cfDNA/ctDNA, CTC, EV/exosomes, methylation, NGS/qPCR/ddPCR, sample quality, contamination, sensitivity and reporting checks.

Open