TruthNexus
Biomarker Validation · Medical

Biomarker evidence that holds up to scrutiny.

95% of candidate biomarkers fail to demonstrate clinical utility. Most validation pipelines pull from a single source, miss contradictions between studies, and don't reconcile AMP, OncoKB, and ESCAT tiers. Skippy Biomarker fuses 20+ sources with Bayesian aggregation, flags contradictions with fragility scoring, and generates FDA RBM-structured evidence packages.

POST /api/biomarker · 200 OK
PD-L1
Non-Small Cell Lung Cancer · Predictive
AMP/ASCO/CAP IA
0.87
Bayesian confidence
CI [0.81–0.93]
Level 1
OncoKB
ESCAT I-A
0.69
OS HR
45.4%
ORR PD-L1+
28.8%
ORR control
CIViCFDA LabelsKEYNOTE-024Retraction clean
95%
Of candidate biomarkers fail clinical utility
142+
Evidence integrations per biomarker assessment
3 frameworks
AMP/ASCO/CAP + OncoKB + ESCAT reconciled
FDA RBM
Regulatory evidence package structure
See It In Action

What a response looks like

Biomarker validation with Bayesian confidence, multi-framework tier emission, and contradiction detection — all three in one API.

POST /api/biomarker · application/jsonsimulation
PD-L1×Non-Small Cell Lung CancerPredictive
0.87
Bayesian confidence
95% CI [0.810.93] · 142 verified findings · 8 sources
AMP/ASCO/CAP IAOncoKB Lvl 1
0.69
OS hazard ratio
[0.560.85]
45.4%
ORR (PD-L1+)
28.8%
ORR (control)
Therapeutic implication · KEYNOTE-024 (NCT02142738) Phase III

Pembrolizumab (PD-1/PD-L1 inhibitor) — FDA-approved first-line for TPS ≥50%

ClinVarCIViCOpenTargetsClinicalTrials.govPubMed+3 moreRetraction clean

Simulated output representative of real API responses. Bayesian Beta-Binomial fusion across 20+ sources. AMP/ASCO/CAP, OncoKB, ESCAT, ACMG tiers.

What It Does

Six capabilities. One API.

POST /api/biomarker

Biomarker validation

Validate any biomarker-disease pair across 20+ curated sources — ClinVar, CIViC, OpenTargets, FDA Labels, ESMO, NCCN, and clinical trial registries. Returns Bayesian confidence with credible interval, role classification (predictive / prognostic / diagnostic), and retraction check.

POST /api/tiers/emit

Multi-framework tier emission

Emit AMP/ASCO/CAP (IA–IVD), OncoKB (Level 1–4), and ESCAT (I-A through IV) tier assignments simultaneously for somatic biomarkers. ACMG Pathogenic/LP/VUS germline classification available for dual-role variants. All three frameworks reconciled in a single call.

POST /api/contradictions/detect

Contradiction detection

Identifies conflicting claims across sources — endpoint mismatch, curation cutoff discrepancies, cohort heterogeneity. Returns fragility index (studies-to-overturn), leave-one-out sensitivity, and root-cause hypothesis. Confidence is adjusted downward when contradictions are unresolved.

GET /api/evidence/package

Regulatory evidence package

Generate FDA RBM qualification-ready or EMA Article 10-scoped evidence packages: executive summary, analytical validation, clinical validation, clinical utility, and references. Structured to LOI → Qualification Plan → Data Submission workflow. Weeks instead of months.

POST /api/biomarker/monitor

Continuous evidence monitoring

Continuous watch on ClinVar, PubMed, and clinical trial registries for new evidence. When incoming data warrants tier reclassification or contradicts the current confidence, an alert fires automatically — without waiting for annual review.

POST /api/ancestry/equity

Ancestry equity audit

Flag biomarkers where clinical evidence derives predominantly from a single ancestry group — a systematic source of validation bias. Returns per-cohort coverage gaps and confidence impact, with guidance on where additional trial data is needed for equitable evidence generation.

Evidence Framework

AMP/ASCO/CAP, OncoKB, ESCAT, and ACMG — reconciled.

Three independent tiering systems use different evidence standards and terminology. Skippy Biomarker emits all frameworks simultaneously — so a single API call tells you where a biomarker stands across every guideline body a regulator or payer will ask about.

AMP/ASCO/CAP Tier IA
Strong clinical significance

FDA-approved therapy available for this biomarker in the tested tumor type. Highest actionability.

AMP/ASCO/CAP Tier IB
Strong clinical significance

Well-powered clinical trial (not yet FDA-approved) demonstrates predictive value with durable response.

AMP/ASCO/CAP Tier IIC/IID
Potential clinical significance

Small study, case reports, or preclinical evidence. Biological plausibility established; clinical validation incomplete.

OncoKB Level 1 / Level 2
FDA-recognized / Standard care

Level 1: FDA-recognized biomarker with approved therapy. Level 2: Standard-of-care biomarker per major guidelines.

ESCAT I-A / I-B
Highest actionability evidence

ESCAT I-A: Prospective randomized trial in the target population. I-B: Prospective non-randomized or retrospective with strong statistical power.

ACMG Pathogenic / LP
Germline classification

Available for dual-role variants. Tavtigian Bayesian posterior — Pathogenic ≥ 0.99, Likely Pathogenic ≥ 0.90. Supports companion diagnostic CDx design.

The contradiction problem

CIViC and OncoKB can disagree on the same biomarker. ASCO GI 2023 and NEJM 2024 can reach opposite conclusions on the same drug-disease pair. Most validation tools don't tell you this.

Skippy Biomarker detects conflicting claims between sources, identifies the root cause (endpoint mismatch, curation cutoff, cohort heterogeneity), and adjusts Bayesian confidence downward when contradictions are unresolved. Fragility index tells you how many studies it would take to overturn the current evidence — a fragility index of 2 is a different clinical reality than a fragility index of 20.

Single-source validation bias
“Validation programs that rely on a single curated database inherit that database's curation cutoff date, inclusion criteria, and ancestral cohort distribution as silent assumptions.”

Skippy Biomarker fuses 20+ sources with TruthFinder source-reputation weighting — sources with retraction histories or curation lag are down-weighted automatically. Ancestry equity audits surface evidence gaps for non-European populations before they become regulatory findings.

Who It's For

Pharma, labs, biotech, and academia

Pharma R&D
Accelerate FDA RBM biomarker qualification and EMA Article 10 pathways without rebuilding the evidence case from scratch. Evidence packages generated in weeks, not months.
Clinical Laboratories
Systematic validation for new biomarker panels meeting CLIA/CAP accreditation requirements. Contradiction detection flags sources that shouldn't be weighted equally.
Biotech / CDx Companies
Evidence-backed validation for companion diagnostic assets — AMP/ASCO/CAP + OncoKB + ESCAT tier emissions support investor diligence and regulatory submissions.
Academic Medical Centers
Rigorous Bayesian validation methodology with full source provenance for biomarker discovery programs, grant applications, and tumor board reporting.
Regulatory

FDA RBM, EMA Article 10, and CLIA/CAP

Evidence packages structured to FDA Biomarker Qualification Program requirements — Letter of Intent, Qualification Plan, Data Submission, and Qualification Opinion stages. EMA Biomarker Qualification Opinion (Article 10 protocol) output also available.

CLIA/CAP analytical validation standards supported for clinical laboratory accreditation. AMP/ASCO/CAP somatic tiering with full evidence provenance meets tumor board reporting standards.

HIPAA-ready with BAA available. Every assessment produces an immutable audit record with all source attributions, Bayesian parameters, tier assignments, and contradiction flags.

HIPAA ReadyFDA RBM AlignedEMA Article 10CLIA/CAP SupportedAMP/ASCO/CAP 2017
Clinical Use

Skippy Biomarker is a decision-support tool for qualified healthcare and research professionals. It does not replace pathologist review, laboratory director sign-out, clinical validation studies, or physician interpretation. All biomarker tier assignments and confidence scores should be confirmed against current institutional guidelines, applicable regulatory approvals, and patient-specific clinical context before use in clinical decisions. HIPAA-ready; BAA available.

See Biomarker in your validation program

We work with pharma R&D, clinical labs, and biotech companies. Let's talk about your biomarker validation problem.