Prediction of premature all-cause mortality: A prospective general population cohort study comparing machine-learning and standard epidemiological approaches

Prognostic modelling using standard methods is well-established, particularly for predicting risk of single diseases. Machine-learning may offer potential to explore outcomes of even greater complexity, such as premature death. This study aimed to develop novel prediction algorithms using machine-learning, in addition to standard survival modelling, to predict premature all-cause mortality. A prospective population cohort of 502,628 participants aged 40-69 years were recruited to the UK Biobank from 2006-2010 and followed-up until 2016. Participants were assessed on a range of demographic, biometric, clinical and lifestyle factors. Mortality data by ICD-10 were obtained from linkage to Office of National Statistics. Models were developed using deep learning, random forest and Cox regression. Calibration was assessed by comparing observed to predicted risks; and discrimination by area under the 'receiver operating curve' (AUC). 14,418 deaths (2.9%) occurred over a total follow-up time of 3,508,454 person-years. A simple age and gender Cox model was the least predictive (AUC 0.689, 95% CI 0.681-0.699). A multivariate Cox regression model significantly improved discrimination by 6.2% (AUC 0.751, 95% CI 0.748-0.767). The application of machine-learning algorithms further improved discrimination by 3.2% using random forest (AUC 0.783, 95% CI 0.776-0.791) and 3.9% using deep learning (AUC 0.790, 95% CI 0.783-0.797). These ML algorithms improved discrimination by 9.4% and 10.1% respectively from a simple age and gender Cox regression model. Random forest and deep learning achieved similar levels of discrimination with no significant difference. Machine-learning algorithms were well-calibrated, while Cox regression models consistently over-predicted risk. Machine-learning significantly improved accuracy of prediction of premature all-cause mortality in this middle-aged population, compared to standard methods. This study illustrates the value of machine-learning for risk prediction within a traditional epidemiological study design, and how this approach might be reported to assist scientific verification.