Privacy enhanced collaborative inference in the Cox proportional hazards model for distributed data

Abstract

Data sharing barriers are paramount challenges arising from multicenter clinical studies where multiple data sources are stored in a distributed fashion at different local study sites. Particularly in the case of time-to-event analysis when global risk sets are needed for the Cox proportional hazards model, access to a centralized database is typically necessary. Merging such data sources into a common data storage for a centralized statistical analysis requires a data use agreement, which is often time-consuming. Furthermore, the construction and distribution of risk sets to participating clinical centers for subsequent calculations may pose a risk of revealing individual-level information. We propose a new collaborative Cox model that eliminates the need for accessing the centralized database and constructing global risk sets but needs only the sharing of summary statistics with significantly smaller dimensions than risk sets. Thus, the proposed collaborative inference enjoys maximal protection of data privacy. We show theoretically and numerically that the new distributed proportional hazards model approach has little loss of statistical power when compared to the centralized method that requires merging the entire data. We present a renewable sieve method to establish large-sample properties for the proposed method. We illustrate its performance through simulation experiments and a real-world data example from patients with kidney transplantation in the Organ Procurement and Transplantation Network (OPTN) to understand the factors associated with the 5-year death-censored graft failure (DCGF) for patients who underwent kidney transplants in the US.