Box 1.

: Etiology versus prediction key characteristics

	Etiology	Prediction
Research question	Objective is to find a causal relation between exposure(s) and outcome(s)	Objective is to predict or diagnose outcome or improve prediction of an outcome in individuals
Statistical approach	Controls for confounding or mediation analysis, using knowledge and assumptions of causal structure and pathways	Develop and/or validate a multivariable model that contains variables (predictors) based on their ability to predict/diagnose the outcome and usability in practice
Presentation of results	Relative risk or risk difference given the exposure, minimizing bias	Measures of the predictive or diagnostic performance of the multivariable model (e.g. discrimination and calibration)
Discussion and interpretation of results	Causal interpretation and/or recognition limitations that preclude causal inference	Proposed use of the prediction model, for example for risk stratification or prediction of prognosis/diagnosis on an individual level, and/or limitations that preclude use (e.g. poor calibration, need for further validation)