Non-linear relationships in clinical research

ABSTRACT True linear relationships are rare in clinical data. Despite this, linearity is often assumed during analyses, leading to potentially biased estimates and inaccurate conclusions. In this introductory paper, we aim to first describe—in a non-mathematical manner—how to identify non-linear relationships. Various methods are then discussed that can be applied to deal with non-linearity, including transformations, polynomials, splines and generalized additive models, along with their strengths and weaknesses. Finally, we illustrate the use of these methods with a practical example from nephrology, providing guidance on how to report the results from non-linear relationships.