ACCEPT 3.0: Recalibrating ACute COPD Exacerbation Prediction Tool (ACCEPT) for global use

Abstract Background The ACute COPD Exacerbation Prediction Tool (ACCEPT) is an algorithm for predicting 12-month risk of chronic obstructive pulmonary disease (COPD) exacerbations. To make it suitable for international use, we externally validated and recalibrated ACCEPT 2.0 to incorporate country-specific background exacerbation risk, using multi-country data from NOVELTY (a NOVEL observational longiTudinal studY). Methods Our study cohort included patients aged $$\:\ge\:$$ 40 years with physician-diagnosed COPD and $$\:\ge\:$$ 30 days of follow-up. We predicted the occurrence of any moderate-to-severe (primary endpoint) and severe (secondary) exacerbations at 12 months, using country-level random effects to account for between-country differences in background exacerbation risks unexplained by predictor effects. We assessed model performance via discrimination, calibration, and net benefit. Results The analysis sample comprised 5,181 patients (59.4% male, mean age at baseline 66.5 years) from 18 countries, with a mean follow-up of 357 days. 12-month risks ranged between 0.11 and 0.46 (mean = 0.26) for moderate-to-severe and 0.03–0.21 (mean = 0.08) for severe exacerbations. Without country-level adjustment, ACCEPT 2.0’s area under the receiver operating characteristic curve (AUROC) was 0.73 (95% CI 0.72–0.75) and 0.76 (95% CI 0.73–0.78) for moderate-to-severe and severe exacerbations, respectively. However, ACCEPT 2.0 consistently overpredicted risks (observed-to-expected [O/E] risk ratio = 0.57 [95% CI 0.54–0.60] and 0.51 [95% CI 0.46–0.56]). After country-level recalibration, ACCEPT 3.0 showed similar AUROCs (0.75 and 0.76) but substantially improved calibration (O/E ratios: 0.99 [95% CI 0.94–1.05] and 0.99 [95% CI 0.90–1.09]). The net benefit of ACCEPT 3.0 exceeded ACCEPT 2.0 across treatment thresholds of 5%-20%. Conclusion Recalibrating ACCEPT 2.0 with country-level effects significantly improved calibration of COPD exacerbation risks. The resulting ACCEPT 3.0 is expected to provide higher clinical utility across a range of treatment thresholds.