# AI Trial-Eligibility Reproducibility + Representative-Population Snapshot

**== SAMPLE / GENERIC EXAMPLE -- SYNTHETIC DATA, NOT A CLIENT ENGAGEMENT ==**

**Format:** contrarianAI Independent-Verifier $499 Snapshot (v0.9 sensor)
**Snapshot generation date:** 2026-07-22
**Snapshot ID:** CAI-PH-GEN-DEMO-9a9603a3a830c05b0dac14c2

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## 1. Scope of Snapshot

This SAMPLE Snapshot addresses a synthetic mid-cap biopharma sponsor's AI-assisted patient-eligibility classifier operating on an oncology Phase III trial. Scenario details:

- **Sponsor profile:** mid-cap biopharma (~$500M-$5B market cap) running an oncology Phase III trial
- **AI system in scope:** trial-eligibility classifier (mock model version trial-eligibility-classifier-v2.8.1, training cutoff 2026-01-15)
- **Audit period:** 2026-04-15 through 2026-07-13 (90 days)
- **Total screenings analyzed:** 4,969
- **Baseline window:** first 30 days (1,572 screenings)
- **Regulatory framework applied:**
  - 21 CFR Part 11 (Electronic Records + Electronic Signatures -- reproducibility requirements)
  - FDA Guidance for Industry: Diversity Plans to Improve Enrollment (April 2022)
  - FDA AI/ML SaMD Action Plan (2021, updates 2024-2026)
  - FDA Predetermined Change Control Plan (PCCP) Draft Guidance (2023)
  - ICH E6(R3) GCP -- Good Clinical Practice (Nov 2023, effective 2025-2026)
  - ICH E8(R1) General Considerations for Clinical Studies (revised for AI-in-trials)
  - ICH E9(R1) Statistical Principles (updates for AI-driven analyses 2026)
  - EMA Reflection Paper on AI in Medicinal Product Lifecycle (2023) + EMA Concept Paper
  - 21st Century Cures Act Section 3013 (Real-World Evidence + representative-population requirements)
  - FDA CDER Center for Excellence in Regulatory Decision Science AI Framework
  - HIPAA Section 164 (patient data privacy in AI training / inference)
  - IRB Common Rule 45 CFR 46 (AI-driven eligibility decision review)

---

## 2. Sensor summary

- **Sensor version:** contrarianAI-distsensor-v0.9
- **Sensor family:** distributional-shape (independent of production model family)
- **Independence:** sensor operates on the trial-eligibility AI's output stream only. Distinct from the production model family. Different mathematical basis (distributional-shape statistics vs gradient-boosted classifier). Different retention pipeline. contrarianAI holds no equity, employment, or vendor relationship with any clinical-AI vendor (Deep 6 AI / TrialGPT / Antidote / Unlearn / QuantHealth / Owkin / any similar), no CRO relationship (IQVIA / Parexel / ICON / PPD / Syneos), and no EDC / eTMF / CTMS vendor relationship (Veeva / Medidata / Oracle Clinical One / Castor).

- **Detection thresholds active:**
  - Mean-shift threshold: 1.5 standard deviations from baseline
  - Variance-ratio threshold: 1.5x baseline
  - KL-divergence threshold: 0.2
  - Cohort representative-population-differential threshold: 12% shift across cohorts

---

## 3. Findings summary

- **Total drift events detected:** 15
- **High severity:** 10
- **Medium severity:** 5
- **First drift day (post-baseline):** Day 44
- **Critical representative-population-differential signal flagged:** NO

---

## 4. Overall determination

**CATEGORY C -- INSUFFICIENT FOR ATTESTATION**

Multiple high-severity distributional-drift events detected in the AI trial-eligibility classifier across the audit period. Sponsor should not represent the trial-eligibility AI as 21 CFR Part 11-defensible or FDA-Diversity-Plan-compliant until named remediation completes and independent re-audit confirms closure. Findings materially affect the sponsor's ability to answer FDA Bioresearch Monitoring Program inspection questions, EMA scientific advice inquiries, ICH E6(R3) essential-documents review, DSMB safety-signal investigations, and IRB continuing-review responses.

---

## 5. The 3 fix-first items scoped to this AI surface

1. **Freeze or hold-for-investigator-review** all post-drift AI-generated eligibility decisions in Cohort P3 (age 65+, 3+ comorbidities, minority representation) pending representative-population validation per FDA Guidance for Industry: Diversity Plans to Improve Enrollment (April 2022). Document the pause, investigator-review override criteria, and resumption gate in the trial's Diversity Plan appendix + IRB continuing-review notification.
2. **Retain evidence artifacts** for every screening in the audit period -- patient-screening record, inclusion/exclusion state, model version pin, decision hash, tool-call trace, config state at decision-time -- for the full audit period per 21 CFR Part 11 Section 11.10 electronic-records retention + ICH E6(R3) essential-documents requirements. Retention duration = trial conclusion + FDA record-retention horizon (15 years post-NDA/BLA approval for pivotal-trial records; longer under Part 11 and sponsor SOP). Preservation-hold notifications should be issued to all site EDCs, the eTMF vendor, and the AI-classifier host now.
3. **Add adaptive drift-monitoring** to production trial-eligibility pipeline. Annual sponsor QA is insufficient given the between-audit blind spot where FDA Bioresearch Monitoring Program inspection findings, DSMB safety-signal reviews, and IRB continuing-review responses compound. Real-time per-cohort representative-population-differential monitoring on the AI output stream is the operational fix.

---

## 6. Detailed drift events

Each event includes date, sensor type, affected patient cohort, severity, and plain-language detail describing what the sensor observed in the trial-eligibility AI's decision stream.

### Day 44 (2026-05-29) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.784). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.7844

### Day 44 (2026-05-29) -- cohort_distribution_divergence (cohort P5)
- **Severity:** high
- **Detail:** Cohort P5 score distribution shape has diverged from baseline (KL=0.828). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.8282

### Day 44 (2026-05-29) -- cohort_distribution_divergence (cohort P1)
- **Severity:** medium
- **Detail:** Cohort P1 score distribution shape has diverged from baseline (KL=0.210). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.2103

### Day 51 (2026-06-05) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=1.126). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 1.1259

### Day 51 (2026-06-05) -- cohort_mean_shift (cohort P3)
- **Severity:** medium
- **Detail:** Cohort P3 eligibility-exclusion score mean shifted +24.77 points (Z=1.69). New rate risks representative-population-differential signal if disparity vs other segments persists.

### Day 51 (2026-06-05) -- cohort_distribution_divergence (cohort P5)
- **Severity:** medium
- **Detail:** Cohort P5 score distribution shape has diverged from baseline (KL=0.263). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.2629

### Day 58 (2026-06-12) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.822). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.8225

### Day 58 (2026-06-12) -- cohort_distribution_divergence (cohort P5)
- **Severity:** high
- **Detail:** Cohort P5 score distribution shape has diverged from baseline (KL=0.727). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.7268

### Day 65 (2026-06-19) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.752). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.7516

### Day 72 (2026-06-26) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.916). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.9161

### Day 72 (2026-06-26) -- cohort_distribution_divergence (cohort P5)
- **Severity:** high
- **Detail:** Cohort P5 score distribution shape has diverged from baseline (KL=0.448). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.4477

### Day 72 (2026-06-26) -- cohort_mean_shift (cohort P3)
- **Severity:** medium
- **Detail:** Cohort P3 eligibility-exclusion score mean shifted +22.32 points (Z=1.53). New rate risks representative-population-differential signal if disparity vs other segments persists.

### Day 79 (2026-07-03) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.782). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.7818

### Day 86 (2026-07-10) -- cohort_distribution_divergence (cohort P3)
- **Severity:** high
- **Detail:** Cohort P3 score distribution shape has diverged from baseline (KL=0.917). Bimodal-emergence or long-tail-shift likely.
- **KL-divergence:** 0.9172

### Day 86 (2026-07-10) -- cohort_mean_shift (cohort P3)
- **Severity:** medium
- **Detail:** Cohort P3 eligibility-exclusion score mean shifted +22.33 points (Z=1.53). New rate risks representative-population-differential signal if disparity vs other segments persists.

---

## 7. Counterparty-question rehearsal

**FDA / EMA / ICH E6(R3) / DSMB / IRB counterparty-question the sponsor's own regulatory affairs and clinical development leads would demand:**

> "Reproduce this AI-generated eligibility decision from Day 47 including the patient's primary diagnosis, comorbidity profile at screening, inclusion/exclusion criteria state, model version, eligibility-score, and lane routed -- as a defensible record we can produce for FDA inspection (including Bioresearch Monitoring Program), EMA scientific advice, ICH E6(R3) essential-documents review, DSMB safety-signal investigation, or IRB continuing-review response."

**Sample screening decisions from Day 47:**

| Screening ID | Exclusion Score | Lane | Model Version | Decision Hash |
|--------------|-----------------|------|---------------|---------------|
| SCR-002534 | 74.67 | Ineligible / Exclude | trial-eligibility-classifier-v2.8.1 | `tec-002534` |
| SCR-002533 | 30.47 | Eligible / Enroll | trial-eligibility-classifier-v2.8.1 | `tec-002533` |
| SCR-002532 | 43.12 | Further Screening / Investigator Review | trial-eligibility-classifier-v2.8.1 | `tec-002532` |
| SCR-002531 | 66.15 | Ineligible / Exclude | trial-eligibility-classifier-v2.8.1 | `tec-002531` |
| SCR-002525 | 74.05 | Ineligible / Exclude | trial-eligibility-classifier-v2.8.1 | `tec-002525` |

**Reproduction status:** all 5 sampled Day-47 screening decisions can be reproduced with defensible-records match: model version pinned, decision hash cryptographically bound, input data (patient cohort + primary diagnosis + ECOG performance status + prior-therapy lines + comorbidity count + days-to-randomization-target at screening-time) retained via decision-provenance record. Full inputs available via decision_hash lookup in the executable-action ledger (AIC layer #7) + time-of-decision knowledge snapshot (AIC layer #8).

**Retention:** artifacts retained for the FDA pivotal-trial record-retention horizon (15 years post-NDA/BLA approval; longer under sponsor SOP and 21 CFR Part 11 Section 11.10(c) electronic-records retention).

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## 8. What full Enterprise Attestation adds beyond this Snapshot

This $499 Snapshot addresses ONE AI system (trial-eligibility classifier) at the SAMPLE sponsor. A full Enterprise Attestation ($35-55K / 3-6 weeks) covers:

- **All 8 AIC layers** (this Snapshot covers layers 1-4 + 6; Enterprise adds layers 5, 7, 8)
- **Full AI surface inventory** (trial-eligibility classifier + eSource/EDC data extraction + adverse-event narrative generation + protocol-deviation classifier + PK/PD simulation assistant + medical-writing AI + safety-signal review AI -- every AI-touched surface in the clinical operations stack)
- **Signed regulator-facing attestation deliverable** (this Snapshot = internal-use PDF; Enterprise = signed statement suitable for FDA Type C meeting submission, EMA scientific advice package, ICH E6(R3) essential-documents inclusion, DSMB pre-read, IRB continuing-review response, or investor / diligence-partner review)
- **On-site scoping session with your team** (this Snapshot = data-driven only; Enterprise = on-ground with your Chief Medical Officer + VP Regulatory Affairs + Clinical Operations lead + IT/CIO + eTMF admin)
- **30/60/90 remediation roadmap w/ named owners + milestones**
- **Adaptive drift-monitoring implementation guidance** tied to your PCCP submission
- **Re-audit cadence recommendation tied to your DSMB safety-review cycle**

**Baseline Audit ($2,500 / 5 days) is the intermediate tier** -- gap map + measurable test + 30/60/90 roadmap on ONE AI surface. Snapshot credit applies to Baseline OR Enterprise upgrade within 30 days.

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## 9. Independent-verifier declaration

I, Kevin Luddy, as principal of contrarianAI LLC, personally attest that:

1. contrarianAI is not an employee, contractor, equity holder, or vendor of the audited sponsor or any of its clinical-AI vendors (Deep 6 AI, TrialGPT, Antidote, Unlearn, QuantHealth, Owkin, or any similar), any CRO (IQVIA, Parexel, ICON, PPD, Syneos), or any EDC / eTMF / CTMS vendor (Veeva, Medidata, Oracle Clinical One, Castor).
2. Assessment tools (distributional-shape sensor, retrieval-auditor, tool-call-grader, prompt-drift-sensor, predictor-corrector, router-drift-sensor) use model families and evaluation methods distinct from those in production at the audited sponsor.
3. This Snapshot is based on the data-sample submitted by the buyer. Changes to the audited sponsor's infrastructure after the Snapshot date are outside this Snapshot's scope.
4. Underlying audit evidence is retained for the Snapshot horizon and will be made available for legitimate regulatory / audit / counterparty inquiry with appropriate legal process, including FDA Bioresearch Monitoring Program requests, EMA scientific-advice inquiries, ICH E6(R3) essential-documents review, DSMB safety-signal investigation, and IRB continuing-review response.

**Signed:** Kevin Luddy, Principal, contrarianAI LLC
**Date:** 2026-07-22
**Retention key:** `9a9603a3a830c05b0dac14c2`

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## 10. Charts + artifacts

- `chart_ph_distributional_drift.png` -- 7-day rolling mean eligibility-exclusion score per patient cohort over the 90-day period
- `chart_ph_baseline_vs_drifted.png` -- Cohort P3 baseline vs recent eligibility-exclusion score distribution (largest observed drift)
- `chart_ph_lane_shift.png` -- Eligibility-lane rate per cohort, baseline vs recent
- `ph_drift_analysis.json` -- machine-readable analysis + event metadata
- `ph_dataset.csv` -- synthetic 90-day trial-eligibility screening input data
- `ph_agent_decisions.csv` -- trial-eligibility AI output + scored screening decisions

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*End of Snapshot CAI-PH-GEN-DEMO-9a9603a3a830c05b0dac14c2*

**== END OF SAMPLE -- YOUR ACTUAL $499 SNAPSHOT WILL LOOK STRUCTURALLY IDENTICAL BUT WITH YOUR SPONSOR'S DATA + AI SYSTEM + TRIAL PHASE + INDICATION + REGULATORY-FRAMEWORK-CITATIONS ==**

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## To purchase YOUR sponsor's $499 Snapshot:

1. Visit: **contrarianai-landing.onrender.com/pharma-snapshot.html**
2. Click **Buy $499** -- Stripe direct-buy, no procurement approval
3. Complete intake form (~2 min): name your AI system + submit 100-1000 anonymized eligibility-screening decision records
4. Report PDF delivered via email within 3 business days

**Snapshot credit ($499) applies to upgrade within 30 days:**
- **Baseline Audit** ($2,500 / 5 days) -- Snapshot credit = $499 off
- **Enterprise Attestation** ($35-55K / 3-6 weeks) -- Snapshot credit = $499 off

Book a call: **cal.com/kevin-luddy-0dlzuu**