Modeling the covariates effects on the hazard function by piecewise exponential artificial neural networks : an application to a controlled clinical trial on renal carcinoma

BACKGROUND: In exploring the time course of a disease to support or generate biological hypotheses, the shape of the hazard function provides relevant information. For long follow-ups the shape of hazard function may be complex, with the presence of multiple peaks. In this paper we present the use of a neural network extension of the piecewise exponential model to study the shape of the hazard function in time in dependence of covariates. The technique is applied to a dataset of 247 renal cell carcinoma patients from a randomized clinical trial. RESULTS: An interaction effect of treatment with number of metastatic lymph nodes but not with pathologic T-stage is highlighted. CONCLUSIONS: Piecewise Exponential Artificial Neural Networks demonstrate a clinically useful and flexible tool in assessing interaction or time-dependent effects of the prognostic factors on the hazard function

Self-Supervised Time-to-Event Modeling with Structured Medical Records

Time-to-event (TTE) models are used in medicine and other fields for estimating the probability distribution of the time until a specific event occurs. TTE models provide many advantages over classification using fixed time horizons, including naturally handling censored observations, but require more parameters and are challenging to train in settings with limited labeled data. Existing approaches, e.g. proportional hazards or accelerated failure time, employ distributional assumptions to reduce parameters but are vulnerable to model misspecification. In this work, we address these challenges with MOTOR (Many Outcome Time Oriented Representations), a self-supervised model that leverages temporal structure found in collections of timestamped events in electronic health records (EHR) and health insurance claims. MOTOR uses a TTE pretraining objective that predicts the probability distribution of times when events occur, making it well-suited to transfer learning for medical prediction tasks. Having pretrained on EHR and claims data of up to 55M patient records (9B clinical events), we evaluate performance after finetuning for 19 tasks across two datasets. Task-specific models built using MOTOR improve time-dependent C statistics by 4.6% over state-of-the-art while greatly improving sample efficiency, achieving comparable performance to existing methods using only 5% of available task data

Deep Learning for Survival Analysis: A Review

The influx of deep learning (DL) techniques into the field of survival analysis in recent years, coupled with the increasing availability of high-dimensional omics data and unstructured data like images or text, has led to substantial methodological progress; for instance, learning from such high-dimensional or unstructured data. Numerous modern DL-based survival methods have been developed since the mid-2010s; however, they often address only a small subset of scenarios in the time-to-event data setting - e.g., single-risk right-censored survival tasks - and neglect to incorporate more complex (and common) settings. Partially, this is due to a lack of exchange between experts in the respective fields. In this work, we provide a comprehensive systematic review of DL-based methods for time-to-event analysis, characterizing them according to both survival- and DL-related attributes. In doing so, we hope to provide a helpful overview to practitioners who are interested in DL techniques applicable to their specific use case as well as to enable researchers from both fields to identify directions for future investigation. We provide a detailed characterization of the methods included in this review as an open-source, interactive table: https://survival-org.github.io/DL4Survival. As this research area is advancing rapidly, we encourage the research community to contribute to keeping the information up to date.Comment: 24 pages, 6 figures, 2 tables, 1 interactive tabl

Computational Intelligence Methods for Bioinformatics and Biostatistics : 10th International Meeting, CIBB 2013, Nice, France, June 20-22, 2013, Revised Selected Papers

International audienc

The risk of re-intervention after endovascular aortic aneurysm repair

This thesis studies survival analysis techniques dealing with censoring to produce predictive tools that predict the risk of endovascular aortic aneurysm repair (EVAR) re-intervention. Censoring indicates that some patients do not continue follow up, so their outcome class is unknown. Methods dealing with censoring have drawbacks and cannot handle the high censoring of the two EVAR datasets collected. Therefore, this thesis presents a new solution to high censoring by modifying an approach that was incapable of differentiating between risks groups of aortic complications. Feature selection (FS) becomes complicated with censoring. Most survival FS methods depends on Cox's model, however machine learning classifiers (MLC) are preferred. Few methods adopted MLC to perform survival FS, but they cannot be used with high censoring. This thesis proposes two FS methods which use MLC to evaluate features. The two FS methods use the new solution to deal with censoring. They combine factor analysis with greedy stepwise FS search which allows eliminated features to enter the FS process. The first FS method searches for the best neural networks' configuration and subset of features. The second approach combines support vector machines, neural networks, and K nearest neighbor classifiers using simple and weighted majority voting to construct a multiple classifier system (MCS) for improving the performance of individual classifiers. It presents a new hybrid FS process by using MCS as a wrapper method and merging it with the iterated feature ranking filter method to further reduce the features. The proposed techniques outperformed FS methods based on Cox's model such as; Akaike and Bayesian information criteria, and least absolute shrinkage and selector operator in the log-rank test's p-values, sensitivity, and concordance. This proves that the proposed techniques are more powerful in correctly predicting the risk of re-intervention. Consequently, they enable doctors to set patients’ appropriate future observation plan

Piecewise Exponential Artificial Neural Networks (PEANN) for Modeling Hazard Function with Right Censored Data

The hazard function plays an important role in the study of disease dynamics in survival analysis. Longer follow-up for various kinds of cancer, particularly breast cancer, has made it possible the observation of complex shapes of the hazard function of occurrence of metastasis and death. The identification of the correct hazard shape is important both for formulation and support of biological hypotheses on the mechanism underlying the disease. In this paper we propose the use of a neural network to model the shape of the hazard function in time in dependence of covariates extending the piecewise exponential model. The use of neural networks accommodates a greater flexibility in the study of the hazard shape