Outcome prediction models incorporating clinical variables for Head and Neck Squamous cell Carcinoma: A systematic review of methodological conduct and risk of bias

Multiple outcome prediction models have been developed for Head and Neck Squamous Cell Carcinoma (HNSCC). This systematic review aimed to identify HNSCC outcome prediction model studies, assess their methodological quality and identify those with potential utility for clinical practice. Inclusion criteria were mucosal HNSCC prognostic prediction model studies (development or validation) incorporating clinically available variables accessible at time of treatment decision making and predicting tumour-related outcomes. Eligible publications were identified from PubMed and Embase. Methodological quality and risk of bias were assessed using the checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies (CHARMS) and prediction model risk of bias assessment tool (PROBAST). Eligible publications were categorised by study type for reporting. 64 eligible publications were identified; 55 reported model development, 37 external validations, with 28 reporting both. CHARMS checklist items relating to participants, predictors, outcomes, handling of missing data, and some model development and evaluation procedures were generally well-reported. Less well-reported were measures accounting for model overfitting and model performance measures, especially model calibration. Full model information was poorly reported (3/55 model developments), specifically model intercept, baseline survival or full model code. Most publications (54/55 model developments, 28/37 external validations) were found to have high risk of bias, predominantly due to methodological issues in the PROBAST analysis domain. The identified methodological issues may affect prediction model accuracy in heterogeneous populations. Independent external validation studies in the local population and demonstration of clinical impact are essential for the clinical implementation of outcome prediction models.