ACCEPT 2·0: Recalibrating and externally validating the Acute COPD exacerbation prediction tool (ACCEPT)

BACKGROUND: The Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Prediction Tool (ACCEPT) was developed for individualised prediction of COPD exacerbations. ACCEPT was well calibrated overall and had a high discriminatory power, but overestimated risk among individuals without recent exacerbations. The objectives of this study were to 1) fine-tune ACCEPT to make better predictions for individuals with a negative exacerbation history, 2) develop more parsimonious models, and 3) externally validate the models in a new dataset. METHODS: We recalibrated ACCEPT using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE, a three-year observational study, 1,803 patients, 2,117 exacerbations) study by applying non-parametric regression splines to the predicted rates. We developed three reduced versions of ACCEPT by removing symptom score and/or baseline medications as predictors. We examined the discrimination, calibration, and net benefit of ACCEPT 2·0 in the placebo arm of the Towards a Revolution in COPD Health (TORCH, a three-year randomised clinical trial of inhaled therapies in COPD, 1,091 patients, 1,064 exacerbations) study. The primary outcome for prediction was the occurrence of ≥2 moderate or ≥1 severe exacerbation in the next 12 months; the secondary outcomes were prediction of the occurrence of any moderate/severe exacerbation or any severe exacerbation. FINDINGS: ACCEPT 2·0 had an area-under-the-curve (AUC) of 0·76 for predicting the primary outcome. Exacerbation history alone (current standard of care) had an AUC of 0·68. The model was well calibrated in patients with positive or negative exacerbation histories. Changes in AUC in reduced versions were minimal for the primary outcome as well as for predicting the occurrence of any moderate/severe exacerbations (ΔAUC<0·011), but more substantial for predicting the occurrence of any severe exacerbations (ΔAUC<0·020). All versions of ACCEPT 2·0 provided positive net benefit over the use of exacerbation history alone for some range of thresholds. INTERPRETATION: ACCEPT 2·0 showed good calibration regardless of exacerbation history, and predicts exacerbation risk better than current standard of care for a range of thresholds. Future studies need to investigate the utility of exacerbation prediction in various subgroups of patients. FUNDING: This study was funded by a team grant from the Canadian Institutes of Health Research (PHT 178432).