Flexible modeling of ratio outcomes in clinical and epidemiological research.

Abstract

In medical studies one frequently encounters ratio outcomes. For modeling these right-skewed positive variables, two approaches are in common use. The first one assumes that the outcome follows a normal distribution after transformation (e.g. a log-normal distribution), and the second one assumes gamma distributed outcome values. Classical regression approaches relate the mean ratio to a set of explanatory variables and treat the other parameters of the underlying distribution as nuisance parameters. Here, more flexible extensions for modeling ratio outcomes are proposed that allow to relate all the distribution parameters to explanatory variables. The models are embedded into the framework of generalized additive models for location, scale and shape (GAMLSS), and can be fitted using a component-wise gradient boosting algorithm. The added value of the new modeling approach is demonstrated by the analysis of the LDL/HDL cholesterol ratio, which is a strong predictor of cardiovascular events, using data from the German Chronic Kidney Disease Study. Particularly, our results confirm various important findings on risk factors for cardiovascular events.