Neural Networks for Survival Prediction in Medicine Using Prognostic Factors: A Review and Critical Appraisal

Survival analysis deals with the expected duration of time until one or more events of interest occur. Time to the event of interest may be unobserved, a phenomenon commonly known as right censoring, which renders the analysis of these data challenging. Over the years, machine learning algorithms have been developed and adapted to right-censored data. Neural networks have been repeatedly employed to build clinical prediction models in healthcare with a focus on cancer and cardiology. We present the first ever attempt at a large-scale review of survival neural networks (SNNs) with prognostic factors for clinical prediction in medicine. This work provides a comprehensive understanding of the literature (24 studies from 1990 to August 2021, global search in PubMed). Relevant manuscripts are classified as methodological/technical (novel methodology or new theoretical model; 13 studies) or applications (11 studies). We investigate how researchers have used neural networks to fit survival data for prediction. There are two methodological trends: either time is added as part of the input features and a single output node is specified, or multiple output nodes are defined for each time interval. A critical appraisal of model aspects that should be designed and reported more carefully is performed. We identify key characteristics of prediction models (i.e., number of patients/predictors, evaluation measures, calibration), and compare ANN's predictive performance to the Cox proportional hazards model. The median sample size is 920 patients, and the median number of predictors is 7. Major findings include poor reporting (e.g., regarding missing data, hyperparameters) as well as inaccurate model development/validation. Calibration is neglected in more than half of the studies. Cox models are not developed to their full potential and claims for the performance of SNNs are exaggerated. Light is shed on the current state of art of SNNs in medicine with prognostic factors. Recommendations are made for the reporting of clinical prediction models. Limitations are discussed, and future directions are proposed for researchers who seek to develop existing methodology.