Survival Analysis Without Sharing of Individual Patient Data by Using a Gaussian Copula.

ABSTRACT

Cox regression and Kaplan-Meier estimations are often needed in clinical research and this requires access to individual patient data (IPD). However, IPD cannot always be shared because of privacy or proprietary restrictions, which complicates the making of such estimations. We propose a method that generates pseudodata replacing the IPD by only sharing non-disclosive aggregates such as IPD marginal moments and a correlation matrix. Such aggregates are collected by a central computer and input as parameters to a Gaussian copula (GC) that generates the pseudodata. Survival inferences are computed on the pseudodata as if it were the IPD. Using practical examples we demonstrate the utility of the method, via the amount of IPD inferential content recoverable by the GC. We compare GC to a summary-based meta-analysis and an IPD bootstrap distributed across several centers. Other pseudodata approaches are also considered. In the empirical results, GC approximates the utility of the IPD bootstrap although it might yield more conservative inferences and it might have limitations in subgroup analyses. Overall, GC avoids many legal problems related to IPD privacy or property while enabling approximation of common IPD survival analyses otherwise difficult to conduct. Sharing more IPD aggregates than is currently practiced could facilitate "second purpose"-research and relax concerns regarding IPD access.