Design matters in patient-level prediction: evaluation of a cohort vs. case-control design when developing predictive models in observational healthcare datasets

Abstract

Background: The design used to create labelled data for training prediction models from observational healthcare databases (e.g., case-control and cohort) may impact the clinical usefulness. We aim to investigate hypothetical design issues and determine how the design impacts prediction model performance. Aim: To empirically investigate differences between models developed using a case-control design and a cohort design. Methods: Using a US claims database, we replicated two published prediction models (dementia and type 2 diabetes) which were developed using a case-control design, and trained models for the same prediction questions using cohort designs. We validated each model on data mimicking the point in time the models would be applied in clinical practice. We calculated the models’ discrimination and calibration-in-the-large performances. Results: The dementia models obtained area under the receiver operating characteristics of 0.560 and 0.897 for the case-control and cohort designs respectively. The type 2 diabetes models obtained area under the receiver operating characteristics of 0.733 and 0.727 for the case-control and cohort designs respectively. The dementia and diabetes case-control models were both poorly calibrated, whereas the dementia cohort model achieved good calibration. We show that careful construction of a case-control design can lead to comparable discriminative performance as a cohort design, but case-control designs over-represent the outcome class leading to miscalibration. Conclusions: Any case-control design can be converted to a cohort design. We recommend that researchers with observational data use the less subjective and generally better calibrated cohort design when extracting labelled data. However, if a carefully constructed case-control design is used, then the model must be prospectively validated using a cohort design for fair evaluation and be recalibrated.