Treatment use in prognostic model research: a systematic review of cardiovascular prognostic studies

Background: Ignoring treatments in prognostic model development or validation can affect the accuracy and transportability of models. We aim to quantify the extent to which the effects of treatment have been addressed in existing prognostic model research and provide recommendations for the handling and reporting of treatment use in future studies. Methods: We first describe how and when the use of treatments by individuals in a prognostic study can influence the development or validation of a prognostic model. We subsequently conducted a systematic review of the handling and reporting of treatment use in prognostic model studies in cardiovascular medicine. Data on treatment use (e.g. medications, surgeries, lifestyle interventions), the timing of their use, and the handling of such treatment use in the analyses were extracted and summarised. Results: Three hundred two articles were included in the review. Treatment use was not mentioned in 91 (30%) articles. One hundred forty-six (48%) reported specific information about treatment use in their studies; 78 (26%) provided information about multiple treatments. Three articles (1%) reported changes in medication use (“treatment drop-in”) during follow-up. Seventy-nine articles (26%) excluded treated individuals from their analysis, 80 articles (26%) modelled treatment as an outcome, and of the 155 articles that developed a model, 86 (55%) modelled treatment use, almost exclusively at baseline, as a predictor. Conclusions: The use of treatments has been partly considered by the majority of CVD prognostic model studies. Detailed accounts including, for example, information on treatment drop-in were rare. Where relevant, the use of treatments should be considered in the analysis of prognostic model studies, particularly when a prognostic model is designed to guide the use of certain treatments and these treatments have been used by the study participants. Future prognostic model studies should clearly report the use of treatments by study participants and consider the potential impact of treatment use on the study findings.