survextrap: a package for flexible and transparent survival extrapolation

Abstract

Background: Health policy decisions are often informed by estimates of long-term survival based primarily on short-term data. A range of methods are available to include longer-term information, but there has previously been no comprehensive and accessible tool for implementing these.

Results: This paper introduces a novel model and software package for parametric survival modelling of individual-level, right-censored data, optionally combined with summary survival data on one or more time periods. It could be used to estimate long-term survival based on short-term data from a clinical trial, combined with longer-term disease registry or population data, or elicited judgements. All data sources are represented jointly in a Bayesian model. The hazard is modelled as an M-spline function, which can represent potential changes in the hazard trajectory at any time. Through Bayesian estimation, the model automatically adapts to fit the available data, and acknowledges uncertainty where the data are weak. Therefore long-term estimates are only confident if there are strong long-term data, and inferences do not rely on extrapolating parametric functions learned from short-term data. The effects of treatment or other explanatory variables can be estimated through proportional hazards or with a flexible non-proportional hazards model. Some commonly-used mechanisms for survival can also be assumed: cure models, additive hazards models with known background mortality, and models where the effect of a treatment wanes over time. All of these features are provided for the first time in an R package, survextrap, in which models can be fitted using standard R survival modelling syntax. This paper explains the model, and demonstrates the use of the package to fit a range of models to common forms of survival data used in health technology assessments.

Conclusions: This paper has provided a tool that makes comprehensive and principled methods for survival extrapolation easily usable.

Keywords: Bayesian; External data; Extrapolation; Survival.