A systematic review of prognostic models for recurrent venous thromboembolism (VTE) post treatment of first unprovoked VTE

Objectives: To review studies developing or validating a prognostic model for individual VTE recurrence risk following cessation of therapy for a first unprovoked VTE. Prediction of recurrence risk is crucial to informing patient prognosis and treatment decisions. The review aims to determine whether reliable prognostic models exist and, if not, what further research is needed within the field. Design: Bibliographic databases (including MEDLINE, EMBASE & the Cochrane library) were searched using index terms relating to the clinical field and prognosis. Screening of titles, abstracts and subsequently full texts was conducted by two reviewers independently using pre-defined criteria. Quality assessment and critical appraisal of included full texts was based on an early version of the PROBAST tool for risk of bias and applicability in prognostic model studies. Setting: Studies in any setting were included. Primary and secondary outcome measures: The primary outcome for the review was the predictive accuracy of identified prognostic models in relation to VTE recurrence risk. Results: Three unique prognostic models were identified including the HERDOO2 score, Vienna prediction model and DASH score. Quality assessment highlighted the Vienna and DASH models were developed with generally strong methodology, but the HERDOO2 model had many methodological concerns. Further, all models were considered at least at moderate risk of bias, primarily due to the need for further external validation before use in practice. Conclusions: Though the Vienna model shows the most promise (based on strong development methodology, applicability, and having some external validation), none of the models can be considered ready for use until further, external and robust validation is performed in new data. Any new models should consider the inclusion of predictors found to be consistently important in existing models (sex, site of index event, D-dimer), and take heed of several methodological issues identified through this review. Study registration: PROSPERO (CRD42013003494) Funding source: NIHR Health Technology Assessment Programme (10/94/02) Strengths and limitations of the study • To our knowledge this is the first systematic review identifying prognostic models for VTE recurrence risk in the unprovoked population, using a robust systematic methodology. • The study is also the first to assess the validity of the existing models in terms of risk of bias and applicability. • We were unable to perform a quantitative analysis of the identified articles due to a lack of homogeneity in many areas, including the predictors used, model types and study populations. • All models require further independent external validation, and as such the true performance of the models in the wider unprovoked population must be assessed in new research.