Clinical Deviation Triage & CAPA AI

Here's the deviation triage draft. One note up front: this is a decision-support draft based on the excerpts provided — final severity grading, UPIRTSO determination, and regulatory submission decisions should be confirmed by a qualified CRA/regulatory affairs reviewer or medical monitor before any sponsor/IRB notification is sent, especially given the Per-Protocol exclusion implications here.

deviation_id: DEV-20260904-001
audit_hash: PENDING_SYSTEM_HASH
algorithm_version: "1.1.0"
generated_at: "2026-09-17T00:00:00Z"
confidence_score: 0.88
status: COMPLETE

classification:
  severity: MAJOR
  justification: >
    The Week 24 visit occurred on Day 185, 14 days outside the protocol-defined
    window of Day 168 +/- 3 days (Section 5.3). The Week 24 echocardiogram and
    Cardiac MRI constitute the trial's primary efficacy endpoint (Section 9.1:
    absolute change in LVEF from baseline to Week 24 via core-lab Cardiac MRI).
    Per Section 9.4, major timing deviations on primary imaging endpoints trigger
    exclusion from the Per-Protocol analysis set. This is a subject-level impact
    on a primary endpoint, not a study-level or systemic safety event, so it is
    graded MAJOR rather than CRITICAL. A secondary, lower-severity issue
    (LABORATORY category: PK sample drawn in an unchilled EDTA tube, contrary
    to lab manual specifications) should be logged separately and referred to
    the central lab/PK team for sample viability assessment.
  ich_gcp_reference: "ICH-GCP E6(R2) Section 4.5.2"
  protocol_section: "5.3; 9.1; 9.4"
  endpoint_impact: PRIMARY_ENDPOINT

regulatory_timeline:
  jurisdiction: US
  is_upirtso: false
  citations:
    - "ICH-GCP E6(R2) 4.5.2"
    - "21 CFR 312.32 (reviewed - not applicable; no safety/IND-reportable event)"
  sponsor_timeline_days: 5
  irb_timeline_days: 0
  identification_date: "2026-09-04"
  sponsor_due_date: "2026-09-11"
  calendar_invites:
    - name: "Sponsor Notification Due"
      date: "2026-09-11"
    - name: "Next Monitoring Visit - Deviation Follow-up"
      date: "TBD_BY_CRA"

capa:
  root_cause: >
    Two converging operational gaps: (1) no designated backup coordinator during
    the primary coordinator's annual leave, leaving no one to manage the visit
    scheduling conflict; (2) the site's MRI scanner recalibration was scheduled
    without cross-checking against upcoming subject visit windows, so the
    equipment outage was not anticipated or mitigated in advance.
  root_cause_category: STAFFING_AND_SCHEDULING_COVERAGE_GAP
  corrective_actions:
    - "Document the deviation in the source record and notify the PI immediately."
    - "Submit protocol deviation report to Sponsor/CRA without delay."
    - "Flag subject CARD-801-089 to biostatistics/data management for Per-Protocol population impact review per Section 9.4."
    - "Notify core imaging lab of the out-of-window Week 24 assessment for endpoint impact classification."
    - "Refer the unchilled PK sample to the central lab to assess sample viability per lab manual specifications."
  preventive_actions:
    - "Implement a mandatory backup-coordinator assignment policy for all planned staff absences at Site 212."
    - "Require equipment maintenance/recalibration scheduling to be cross-checked against the visit tracker before booking."
    - "Add an automated visit-window alert (e.g., 14/7/3-day flags) to the site's scheduling system."
  effectiveness_check:
    scope: "Next 3 subjects enrolled/visiting at Site 212"
    duration_days: 30
    metric: "Zero visit-window deviations attributable to staffing or equipment scheduling conflicts"
    reviewer: "Assigned CRA at next monitoring visit"

routing:
  primary_recipient: "Primary CRA"
  cc_recipients:
    - "Sponsor Clinical Operations"
    - "Site 212 PI"
  method: CTMS_WORKFLOW
  follow_up: "Address at next scheduled monitoring visit; confirm Per-Protocol population impact determination with biostatistics before final report closure."
  escalation_reason: ""

deliverables:
  pdf_report: PENDING_SYSTEM_GENERATION
  ctms_payload:
    deviation_id: DEV-20260904-001
    subject_id: "CARD-801-089"
    site_number: "SITE-212"
    severity: MAJOR
    category_primary: WINDOW
    category_secondary: LABORATORY
    endpoint_impact: PRIMARY_ENDPOINT
    per_protocol_exclusion_flag: true
    sponsor_due_date: "2026-09-11"
  text_report_preview: >
    Subject CARD-801-089 (Site 212) underwent the Week 24 visit 14 days outside
    the protocol window, affecting the primary efficacy endpoint (Cardiac MRI/LVEF)
    and triggering a likely Per-Protocol exclusion per Section 9.4. Root cause:
    lack of backup coordinator coverage plus unplanned MRI downtime. Graded MAJOR;
    sponsor notification due 2026-09-11. A secondary lab-handling deviation
    (unchilled PK tube) has been logged for central lab review.

A few things worth double-checking with a human reviewer: whether the PK sample handling issue should be filed as a fully separate deviation record rather than folded into this one, and whether the biostatistics team's actual Per-Protocol determination changes the endpoint_impact/exclusion flag before this goes into the TMF.