Quantitative prediction error analysis to investigate predictive performance under predictor measurement heterogeneity at model implementation

Background When a predictor variable is measured in similar ways at the derivation and validation setting of a prognostic prediction model, yet both differ from the intended use of the model in practice (i.e., "predictor measurement heterogeneity"), performance of the model at implementation needs to be inferred. This study proposed an analysis to quantify the impact of anticipated predictor measurement heterogeneity.Methods A simulation study was conducted to assess the impact of predictor measurement heterogeneity across validation and implementation setting in time-to-event outcome data. The use of the quantitative prediction error analysis was illustrated using an example of predicting the 6-year risk of developing type 2 diabetes with heterogeneity in measurement of the predictor body mass index.Results In the simulation study, calibration-in-the-large of prediction models was poor and overall accuracy was reduced in all scenarios of predictor measurement heterogeneity. Model discrimination decreased with increasing random predictor measurement heterogeneity.Conclusions Heterogeneity of predictor measurements across settings of validation and implementation reduced predictive performance at implementation of prognostic models with a time-to-event outcome. When validating a prognostic model, the targeted clinical setting needs to be considered and analyses can be conducted to quantify the impact of anticipated predictor measurement heterogeneity on model performance at implementation.