Management of superficial venous thrombosis based on individual risk profiles: protocol for the development and validation of three prognostic prediction models in large primary care cohorts.

Background Superficial venous thrombosis (SVT) is considered a benign thrombotic condition in most patients. However, it also can cause serious complications, such as clot progression to deep venous thrombosis (DVT) and pulmonary embolism (PE). Although most SVT patients are encountered in primary healthcare, studies on SVT nearly all were focused on patients seen in the hospital setting. This paper describes the protocol of the development and external validation of three prognostic prediction models for relevant clinical outcomes in SVT patients seen in primary care: (i) prolonged (painful) symptoms within 14 days since SVT diagnosis, (ii) for clot progression to DVT or PE within 45 days and (iii) for clot recurrence within 12 months. Methods Data will be used from four primary care routine healthcare registries from both the Netherlands and the UK; one UK registry will be used for the development of the prediction models and the remaining three will be used as external validation cohorts. The study population will consist of patients ≥18 years with a diagnosis of SVT. Selection of SVT cases will be based on a combination of ICPC/READ/Snowmed coding and free text clinical symptoms. Predictors considered are sex, age, body mass index, clinical SVT characteristics, and co-morbidities including (history of any) cardiovascular disease, diabetes, autoimmune disease, malignancy, thrombophilia, pregnancy or puerperium and presence of varicose veins. The prediction models will be developed using multivariable logistic regression analysis techniques for models i and ii, and for model iii, a Cox proportional hazards model will be used. They will be validated by internal-external cross-validation as well as external validation. Discussion There are currently no prediction models available for predicting the risk of serious complications for SVT patients presenting in primary care settings. We aim to develop and validate new prediction models that should help identify patients at highest risk for complications and to support clinical decision making for this understudied thrombo-embolic disorder. Challenges that we anticipate to encounter are mostly related to performing research in large, routine healthcare databases, such as patient selection, endpoint classification, data harmonisation, missing data and avoiding (predictor) measurement heterogeneity.