Performance of multivariable risk prediction algorithms in predicting COPD exacerbations: a population-based study

INTRODUCTION: Efficient preventive management of acute exacerbation of chronic obstructive pulmonary disease (COPD) is predicated on accurate risk stratification. We compared the performance of exacerbation history (current standard of care) versus a revised version of a multivariable risk scoring tool (Acute COPD Exacerbation Prediction Tool (ACCEPT)) using primary-care UK data. METHODS: We used validated case definitions to identify diagnosed patients with COPD ≥40 years old from the UK Clinical Practice Research Datalink Aurum (2004-2020). For each patient, a single annual COPD visit was randomly selected as the index date. The outcome was the occurrence of ≥1 moderate/severe exacerbation(s) within a year of the index date. We conducted time-to-event analyses of the latest version of ACCEPT (ACCEPT 2.0) and developed a recalibrated version (ACCEPT 3.0-UK). Model performance was evaluated using discrimination (time-dependent area under the receiver operating characteristic curve (AUC)), calibration and net benefit. RESULTS: The final cohort included 158 384 patients (55.0% male; mean age 71.5 years). ACCEPT 2.0 achieved an AUC of 0.77 for predicting moderate/severe exacerbations, outperforming both any and frequent exacerbator categories (AUC: 0.69 and 0.67, respectively). However, it overpredicted exacerbation events (observed-to-expected (O/E) ratio: 0.81 (95% CI 0.80 to 0.81)). Recalibration resolved this overprediction, yielding O/E ratio of 1.00 (95% CI 0.99 to 1.00), while maintaining discrimination (AUC: 0.77). ACCEPT 3.0-UK was net beneficial and superior to exacerbation history across a wide range of risk thresholds. CONCLUSION: ACCEPT 3.0-UK has substantially higher performance than exacerbation history, quantifies predicted risks for shared decision-making and is likely to confer clinical utility for risk stratification in primary care.