# Stage 4 — Synthetic Data Generation Report

**Pipeline stage:** 4 of 14
**Date:** 2 May 2026
**Author:** IQANOVA AI-QSP Master Pipeline v2.0

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## 4.1 Approach

The v1.3 calibration target table contained only 17 sparse summary points (W52 + W104 endpoints). v2.0 expands this to **370 rows** of figure-level trajectory data: **64 anchor points** lifted directly from published ASCEND, ASCEND-OLE, ASCEND-Peds and ASCEND-Peds 2-year extension reports, plus **306 mechanistically interpolated points** at 4-weekly resolution. Each row is fully provenanced with source ID, type, year, reliability grade (A/B/C), and pipeline role (Calibration / Bridge calibration / Bridge validation / Holdout / External descriptive).

## 4.2 Source registry

| Source ID | Title | Type | Year | Reliability | Rows used |
|---|---|---|---|---|---|
| SRC-ASCEND-ADULT-2022 | Wasserstein et al. 2022 — ASCEND adult Phase II/III primary 12-month | Phase II/III RCT | 2022 | A | 12 |
| SRC-ASCEND-ADULT-OLE-2024 | Wasserstein et al. 2024 — ASCEND-OLE adult open-label 24-month extension | RCT extension | 2024 | A | 7 |
| SRC-ASCEND-PEDS-2022 | Diaz et al. 2022 — ASCEND-Peds Phase I/II 52-week | Paediatric Phase I/II | 2022 | A | 9 |
| SRC-ASCEND-PEDS-2Y-2024 | Diaz et al. 2024 — ASCEND-Peds 2-year extension | Paediatric extension | 2024 | A | 8 |
| SRC-EMA-PI-2024 | EMA Xenpozyme Product Information (consolidated PI biomarker section) | Regulatory PI | 2024 | A | 28 |
| SRC-LITERATURE-INTERP | Mechanistic interpolation between published timepoints | Synthetic (literature-anchored) | 2026 | B | 306 |

**Total: 64 reliability-A anchor rows + 306 reliability-B interpolated rows = 370 rows.**

## 4.3 Endpoint coverage (anchor counts per population × endpoint)

| Endpoint | Adult anchors | Paediatric anchors | Calibration role | Holdout role |
|---|---|---|---|---|
| spleen_volume_pct | 5 | 5 | Calib + Bridge calib | W104 |
| liver_volume_pct  | 5 | 5 | Calib + Bridge calib | W104 |
| DLCO_pct          | 5 | 5 | Calib + Bridge calib | W104 |
| platelet_pct      | 4 | 4 | Calib + Bridge valid | W104 |
| LysoSM_pct        | 5 | 5 | Calib + Bridge calib | W104 |
| Ceramide_pct      | 6 | 6 | Calib + Bridge valid | W104 |
| height_z_change   | – | 4 | External descriptive | W104 |

Two methodological points worth noting. (i) Plasma ceramide trajectories are anchored at six points (week 0, 4, 12, 26, 52, 104) to capture the predicted early-peak-then-decline kinetics from hypothesis H5 (Stage 3); the v1.3 target table contained only the week-52 nadir, which is the reason v1.3 could not represent the dynamics correctly. (ii) Paediatric height-Z is included as External descriptive — it is not coupled mechanistically to the burden ODEs and is fitted by a stand-alone logistic catch-up rate rule.

## 4.4 Files produced

| File | Path | Format |
|---|---|---|
| Long-format dataset | `stage04_data/ASMD_Xenpozyme_QSP_v2_0_synthetic_data.csv` | CSV, 370 rows × 12 cols |
| Provenance workbook | `stage04_data/ASMD_Xenpozyme_QSP_v2_0_data_provenance.xlsx` | XLSX, 4 sheets |
| Calibration JSON | `stage04_data/ASMD_Xenpozyme_QSP_v2_0_synthetic_data.json` | JSON, nested by population/endpoint |
| Generator script | `stage04_data/build_synthetic_data.py` | Python |

**Gate G2 (every datapoint provenanced) — PASS. Gate to Stage 5: OPEN.**
