A visualization tool for continuous reference intervals based on GAMLSS

Abstract

Reference intervals are an important component in the interpretation of medical laboratory findings. Especially in children and adolescents, their limits sometimes can change very rapidly with age. We suggest continuous methods to better represent the age-dependent progression of reference intervals. The generalized additive models for location, scale, and shape parameters (GAMLSS) from the R package gamlss generates continuous percentile plots of laboratory values. A user-friendly Shiny application called AdRI_GAMLSS (Age-dependent Reference Intervals), available at github.com/SandraKla/AdRI_GAMLSS, has been developed for this purpose. Using alkaline phosphatase (ALP) as an example, we obtain different smoothed percentile curves depending on the model used. We demonstrate the superiority of continuously modeled reference intervals compared to fixed age groups and provide the Shiny application AdRI_GAMLSS to make the technique easily accessible to clinicians and other experts.

Keywords

• generalized additive models for location, scale, and shape parameters (gamlss)
• reference intervals
• statistical learning methods