# Validation Plan & Clinical-Study Roadmap

The basis for discussion with neurosurgical partners (e.g., University of Arizona
and Barrow Neurological Institute). This describes how Sulcora moves from
research software to a validated planning aid. It is a plan, not a claim of
completed validation. Regulatory specifics must be confirmed with qualified
regulatory advisers.

## 1. Accuracy metrics (what we measure)

| Metric | Definition | Provisional acceptance target* |
|---|---|---|
| **Target Registration Error (TRE)** | Distance (mm) between the planned target and the achieved/known target in physical space | mean ≤ 1.5 mm; 95th pct ≤ 2.0 mm |
| **Entry-point error** | Distance (mm) between planned and achieved entry | mean ≤ 1.5 mm |
| **Angular error** | Angle (deg) between planned and achieved trajectory | ≤ 2° |
| **Structure-clearance error** | Error in computed distance to a labelled structure vs. ground truth | ≤ 1 mm |
| **Segmentation accuracy** | Dice / surface distance vs. expert annotation for eloquent regions & vessels | Dice ≥ 0.90 on key structures |
| **Deformation-model error** (Phase II) | Predicted vs. measured tissue displacement | ≤ 2 mm |

*Targets are provisional and to be finalised with clinical partners and against
the official ARPA-H Topic 7 metrics once published.

## 2. Staged validation (bench → cadaver → retrospective → prospective)

**Stage A — Phantom / bench.** Anthropomorphic skull-and-brain phantoms with
embedded fiducials of known geometry. Plan trajectories in Sulcora, execute on
a stereotactic frame or test rig, measure TRE/entry/angular error. Fully
controlled ground truth; no human subjects.

**Stage B — Cadaveric.** Plan and execute trajectories in cadaveric specimens
imaged pre/post; compare planned vs. achieved with post-placement CT. Validates
on real tissue and real anatomy. Conducted under institutional anatomical-lab
governance with neurosurgical partners.

**Stage C — Retrospective imaging.** Run Sulcora on de-identified historical
MRI/CT datasets (IRB-approved, data-use agreement). Compare Sulcora plans and
segmentations against expert neurosurgeon plans and annotations. No patient
contact; establishes agreement with expert practice at scale.

**Stage D — Prospective clinical study (planning-aid).** See §4.

## 3. Software quality & risk (medical-device engineering)

- Design controls and a Quality Management System (e.g., ISO 13485) once the
  product path is committed.
- Software lifecycle per **IEC 62304**; risk management per **ISO 14971**;
  usability per **IEC 62366**.
- Requirements traceability, verification tests (the unit-test suite is the seed
  of this), and a documented hazard analysis.
- Cybersecurity and PHI handling controls for any patient data.

## 4. Clinical study design (illustrative)

**Phase 0 / usability:** neurosurgeons plan representative cases in Sulcora;
collect usability (SUS), planning time, and qualitative feedback. No patient
impact.

**Pivotal (planning-aid, non-interventional first):** prospective, multi-reader
study comparing Sulcora-assisted plans to standard-of-care plans on the same
patients' images.
- **Primary endpoint:** agreement of Sulcora trajectory metrics with the
  accepted clinical plan / achieved placement (TRE-equivalent), non-inferiority
  to standard planning.
- **Secondary:** planning time, inter-rater variability, surgeon-reported
  confidence, proximity-warning sensitivity/specificity vs. expert review.
- **Design:** prospective, blinded multi-reader multi-case where feasible; IRB
  approval; informed consent; pre-registered statistical analysis plan and
  sample-size justification powered to the non-inferiority margin.
- **Safety:** as a planning aid used alongside standard navigation, the device
  does not actuate; risk is mis-display/mis-measurement, mitigated by the §3
  controls and by keeping the surgeon in the loop.

Sites: University of Arizona (Tucson/Phoenix) and Barrow Neurological Institute
are natural partners given their neurosurgical volume, robotics expertise, and
research infrastructure.

## 5. Regulatory pathway (to confirm with regulatory counsel)

- Likely **FDA Software as a Medical Device (SaMD)**. A stereotactic planning aid
  may fit an existing device classification (potential **510(k)** with a
  predicate such as cleared surgical-planning/navigation software) or require a
  **De Novo** if no suitable predicate exists.
- Predicate analysis, intended-use statement, and pre-submission (**Q-Sub**)
  meeting with FDA recommended early.
- Robotic/autonomous capability, if pursued later, is a separate and
  substantially higher regulatory burden and is not part of the initial
  submission.

## 6. What the ARPA-H Phase I/II work delivers against this plan

- **Phase I:** automated segmentation of eloquent structures & vasculature
  (enabling real structure-aware risk scoring), the real-time deformation
  surrogate, and Stage A (phantom) + initial Stage C (retrospective) validation,
  with a peer-reviewed accuracy publication.
- **Phase II:** Stage B (cadaveric) and expanded Stage C, hardware-in-the-loop
  robotics integration, QMS/IEC 62304 maturation, and pre-submission engagement.

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*This is clinical-research and engineering planning material, not regulatory,
legal, or medical advice.*
