RESOLVE-IPD: High-Fidelity Individual Patient Data Reconstruction and Uncertainty-Aware Subgroup Meta-Analysis

TL;DR

RESOLVE-IPD is a comprehensive framework that accurately reconstructs individual patient data from published Kaplan-Meier curves and performs uncertainty-aware subgroup meta-analysis, enhancing evidence synthesis in oncology.

Contribution

It introduces a unified method combining high-fidelity IPD reconstruction with uncertainty-aware subgroup inference, addressing key limitations of existing approaches.

Findings

Achieved precise IPD reconstruction with minimal digitization error.

Enabled reliable subgroup analysis with quantified uncertainty.

Validated effectiveness through a meta-analysis in esophageal cancer trials.

Abstract

Individual patient data (IPD) from oncology trials are essential for reliable evidence synthesis but are rarely publicly available, necessitating reconstruction from published Kaplan-Meier (KM) curves. Existing reconstruction methods suffer from digitization errors, unrealistic uniform censoring assumptions, and the inability to recover subgroup-level IPD when only aggregate statistics are available. We developed RESOLVE-IPD, a unified computational framework that enables high-fidelity IPD reconstruction and uncertainty-aware subgroup meta-analysis to address these limitations. RESOLVE-IPD comprises two components. The first component, High-Fidelity IPD Reconstruction, integrates the VEC-KM and CEN-KM modules: VEC-KM extracts precise KM coordinates and explicit censoring marks from vectorized figures, minimizing digitization error, while CEN-KM corrects overlapping censor symbols and eliminates the uniform censoring assumption. The second component, Uncertainty-Aware Subgroup Recovery, employs the MAPLE (Marginal Assignment of Plausible Labels and Evidence Propagation) algorithm to infer patient-level subgroup labels consistent with published summary statistics (e.g., hazard ratio, median overall survival) when subgroup KM curves are unavailable. MAPLE generates ensembles of mathematically valid labelings, facilitating a propagating meta-analysis that quantifies and reflects uncertainty from subgroup reconstruction. RESOLVE-IPD was validated through a subgroup meta-analysis of four trials in advanced esophageal squamous cell carcinoma, focusing on the programmed death ligand 1 (PD-L1)-low population. RESOLVE-IPD enables accurate IPD reconstruction and robust, uncertainty-aware subgroup meta-analyses, strengthening the reliability and transparency of secondary evidence synthesis in precision oncology.