This study quantifies the association between non-adherence to antipsychotic medications and adverse outcomes in individuals with schizophrenia. We frame the problem using survival analysis, focusing on the time to the earliest of several adverse events (early death, involuntary hospitalization, jail booking). We extend standard causal inference methods (T-learner, S-learner, nearest neighbor matching) to utilize various survival models to estimate individual and average treatment effects, where treatment corresponds to medication non-adherence. Analyses are repeated using different amounts of longitudinal information (3, 6, 9, and 12 months). Using data from Allegheny County in western Pennsylvania, we find strong evidence that non-adherence advances adverse outcomes by approximately 1 to 4 months. Ablation studies confirm that county-provided risk scores adjust for key confounders, as their removal amplifies the estimated effects. Subgroup analyses by medication formulation (injectable vs. oral) and medication type consistently show that non-adherence is associated with earlier adverse events. These findings highlight the clinical importance of adherence in delaying psychiatric crises and show that integrating survival analysis with causal inference tools can yield policy-relevant insights. We caution that although we apply causal inference, we only make associative claims and discuss assumptions needed for causal interpretation.

Many ensemble-based models have been proposed to solve machine learning problems in the survival analysis framework, including random survival forests, the gradient boosting machine with weak survival models, ensembles of the Cox models. To extend the set of models, a new ensemble-based model called SurvBETA (the Survival Beran estimator Ensemble using Three Attention mechanisms) is proposed where the Beran estimator is used as a weak learner in the ensemble. The Beran estimator can be regarded as a kernel regression model taking into account the relationship between instances. Outputs of weak learners in the form of conditional survival functions are aggregated with attention weights taking into account the distance between the analyzed instance and prototypes of all bootstrap samples. The attention mechanism is used three times: for implementation of the Beran estimators, for determining specific prototypes of bootstrap samples and for aggregating the weak model predictions. The proposed model is presented in two forms: in a general form requiring to solve a complex optimization problem for its training; in a simplified form by considering a special representation of the attention weights by means of the imprecise Huber's contamination model which leads to solving a simple optimization problem. Numerical experiments illustrate properties of the model on synthetic data and compare the model with other survival models on real data. A code implementing the proposed model is publicly available.

This paper introduces a Random Survival Forest (RSF) method for functional data. The focus is specifically on defining a new functional data structure, the Censored Functional Data (CFD), for dealing with temporal observations that are censored due to study limitations or incomplete data collection. This approach allows for precise modelling of functional survival trajectories, leading to improved interpretation and prediction of survival dynamics across different groups. A medical survival study on the benchmark SOFA data set is presented. Results show good performance of the proposed approach, particularly in ranking the importance of predicting variables, as captured through dynamic changes in SOFA scores and patient mortality rates.

Time-to-event analysis is a branch of statistics that has increased in popularity during the last decades due to its many application fields, such as predictive maintenance, customer churn prediction and population lifetime estimation. In this paper, we review and compare the performance of several prediction models for time-to-event analysis. These consist of semi-parametric and parametric statistical models, in addition to machine learning approaches. Our study is carried out on three datasets and evaluated in two different scores (the integrated Brier score and concordance index). Moreover, we show how ensemble methods, which surprisingly have not yet been much studied in time-to-event analysis, can improve the prediction accuracy and enhance the robustness of the prediction performance. We conclude the analysis with a simulation experiment in which we evaluate the factors influencing the performance ranking of the methods using both scores. Keywords: Ensemble methods, time-to-event analysis, integrated Brier score, concordance index.

Survival analysis is a subfield of statistics concerned with modeling the occurrence time of a particular event of interest for a population. Survival analysis found widespread applications in healthcare, engineering, and social sciences. However, real-world applications involve survival datasets that are distributed, incomplete, censored, and confidential. In this context, federated learning can tremendously improve the performance of survival analysis applications. Federated learning provides a set of privacy-preserving techniques to jointly train machine learning models on multiple datasets without compromising user privacy, leading to a better generalization performance. However, despite the widespread development of federated learning in recent AI research, few studies focus on federated survival analysis. In this work, we present a novel federated algorithm for survival analysis based on one of the most successful survival models, the random survival forest. We call the proposed method Federated Survival Forest (FedSurF). With a single communication round, FedSurF obtains a discriminative power comparable to deep-learning-based federated models trained over hundreds of federated iterations. Moreover, FedSurF retains all the advantages of random forests, namely low computational cost and natural handling of missing values and incomplete datasets. These advantages are especially desirable in real-world federated environments with multiple small datasets stored on devices with low computational capabilities. Numerical experiments compare FedSurF with state-of-the-art survival models in federated networks, showing how FedSurF outperforms deep-learning-based federated algorithms in realistic environments with non-identically distributed data.

Survival analysis is a fundamental tool in medicine, modeling the time until an event of interest occurs in a population. However, in real-world applications, survival data are often incomplete, censored, distributed, and confidential, especially in healthcare settings where privacy is critical. The scarcity of data can severely limit the scalability of survival models to distributed applications that rely on large data pools. Federated learning is a promising technique that enables machine learning models to be trained on multiple datasets without compromising user privacy, making it particularly well-suited for addressing the challenges of survival data and large-scale survival applications. Despite significant developments in federated learning for classification and regression, many directions remain unexplored in the context of survival analysis. In this work, we propose an extension of the Federated Survival Forest algorithm, called FedSurF++. This federated ensemble method constructs random survival forests in heterogeneous federations. Specifically, we investigate several new tree sampling methods from client forests and compare the results with state-of-the-art survival models based on neural networks. The key advantage of FedSurF++ is its ability to achieve comparable performance to existing methods while requiring only a single communication round to complete. The extensive empirical investigation results in a significant improvement from the algorithmic and privacy preservation perspectives, making the original FedSurF algorithm more efficient, robust, and private. We also present results on two real-world datasets demonstrating the success of FedSurF++ in real-world healthcare studies. Our results underscore the potential of FedSurF++ to improve the scalability and effectiveness of survival analysis in distributed settings while preserving user privacy.

Predicting the individual risk of a clinical event using the complete patient history is still a major challenge for personalized medicine. Among the methods developed to compute individual dynamic predictions, the joint models have the assets of using all the available information while accounting for dropout. However, they are restricted to a very small number of longitudinal predictors. Our objective was to propose an innovative alternative solution to predict an event probability using a possibly large number of longitudinal predictors. We developed DynForest, an extension of competing-risk random survival forests that handles endogenous longitudinal predictors. At each node of the tree, the time-dependent predictors are translated into time-fixed features (using mixed models) to be used as candidates for splitting the subjects into two subgroups. The individual event probability is estimated in each tree by the Aalen-Johansen estimator of the leaf in which the subject is classified according to his/her history of predictors. The final individual prediction is given by the average of the tree-specific individual event probabilities. We carried out a simulation study to demonstrate the performances of DynForest both in a small dimensional context (in comparison with joint models) and in a large dimensional context (in comparison with a regression calibration method that ignores informative dropout). We also applied DynForest to (i) predict the individual probability of dementia in the elderly according to repeated measures of cognitive, functional, vascular and neuro-degeneration markers, and (ii) quantify the importance of each type of markers for the prediction of dementia. Implemented in the R package DynForest, our methodology provides a novel and appropriate solution for the prediction of events from any number of longitudinal endogenous predictors.

Many clinical studies require the follow-up of patients over time. This is challenging: apart from frequently observed drop-out, there are often also organizational and financial challenges, which can lead to reduced data collection and, in turn, can complicate subsequent analyses. In contrast, there is often plenty of baseline data available of patients with similar characteristics and background information, e.g., from patients that fall outside the study time window. In this article, we investigate whether we can benefit from the inclusion of such unlabeled data instances to predict accurate survival times. In other words, we introduce a third level of supervision in the context of survival analysis, apart from fully observed and censored instances, we also include unlabeled instances. We propose three approaches to deal with this novel setting and provide an empirical comparison over fifteen real-life clinical and gene expression survival datasets. Our results demonstrate that all approaches are able to increase the predictive performance over independent test data. We also show that integrating the partial supervision provided by censored data in a semi-supervised wrapper approach generally provides the best results, often achieving high improvements, compared to not using unlabeled data.

Scoring systems are highly interpretable and widely used to evaluate time-to-event outcomes in healthcare research. However, existing time-to-event scores are predominantly created ad-hoc using a few manually selected variables based on clinician's knowledge, suggesting an unmet need for a robust and efficient generic score-generating method. AutoScore was previously developed as an interpretable machine learning score generator, integrated both machine learning and point-based scores in the strong discriminability and accessibility. We have further extended it to time-to-event data and developed AutoScore-Survival, for automatically generating time-to-event scores with right-censored survival data. Random survival forest provides an efficient solution for selecting variables, and Cox regression was used for score weighting. We illustrated our method in a real-life study of 90-day mortality of patients in intensive care units and compared its performance with survival models (i.e., Cox) and the random survival forest. The AutoScore-Survival-derived scoring model was more parsimonious than survival models built using traditional variable selection methods (e.g., penalized likelihood approach and stepwise variable selection), and its performance was comparable to survival models using the same set of variables. Although AutoScore-Survival achieved a comparable integrated area under the curve of 0.782 (95% CI: 0.767-0.794), the integer-valued time-to-event scores generated are favorable in clinical applications because they are easier to compute and interpret. Our proposed AutoScore-Survival provides an automated, robust and easy-to-use machine learning-based clinical score generator to studies of time-to-event outcomes. It provides a systematic guideline to facilitate the future development of time-to-event scores for clinical applications.

Recent studies have adopted an approach of selecting accurate and diverse trees based on individual or collective performance within an ensemble for classification and regression problems. This work follows in the wake of these investigations and considers the possibility of growing a forest of optimal survival trees. Initially, a large set of survival trees are grown using the method of random survival forest. The grown trees are then ranked from smallest to highest value of their prediction error using out-of-bag observations for each respective survival tree. The top ranked survival trees are then assessed for their collective performance as an ensemble. This ensemble is initiated with the survival tree which stands first in rank, then further trees are tested one by one by adding them to the ensemble in order of rank. A survival tree is selected for the resultant ensemble if the performance improves after an assessment using independent training data. This ensemble is called an optimal trees ensemble (OSTE). The proposed method is assessed using 17 benchmark datasets and the results are compared with those of random survival forest, conditional inference forest, bagging and a non tree based method, the Cox proportional hazard model. In addition to improve predictive performance, the proposed method reduces the number of survival trees in the ensemble as compared to the other tree based methods. The method is implemented in an R package called "OSTE".