This week, I covered the story of Casey Harrell --a man with ALS who is "the first power user" of a brain implant, according to the researchers who worked with him. Harrell is paralyzed and unable to speak coherently without the device. He has now spent almost three years using a brain-computer interface (BCI) that enables him to "speak," surf the web, and perform his job as a climate activist, largely independently. Since Harrell was implanted with the device, in July 2023, a team at the University of California, Davis, has worked with him to adjust and improve its offerings. They've refined its accuracy, for example.

The Download: the first brain implant power user and South Korea's AI obsession Plus: The US says it restricted Anthropic AI over foreign intelligence risks. This man with ALS is the first "power user" of a brain implant that lets him speak Casey Harrell has had a set of electrodes embedded in his brain for almost three years. Harrell, who has ALS and is paralyzed, first used his brain-computer interface (BCI) to "speak" in 2023. Since then, he's clocked thousands of hours of use. Harrell can now use the device largely independently. His team has added new features to it, and he also uses it to surf the web and perform his job.

Casey Harrell has had a set of electrodes embedded in his brain for almost three years. Harrell, who has amyotrophic lateral sclerosis (ALS) and is paralyzed, first used his brain-computer interface (BCI) to "speak" sentences with the help of a research team in 2023. Since then, Harrell has clocked thousands of hours of use. He can use the device largely independently, once he's been "plugged in" with the help of a carer. His team has added new features to it, and Harrell also uses it to surf the web and perform his job.

Survival analysis often relies on Cox models, assuming both linearity and proportional hazards (PH). This study evaluates machine and deep learning methods that relax these constraints, comparing their performance with penalized Cox models on a benchmark of three synthetic and three real datasets. In total, eight different models were tested, including six non-linear models of which four were also non-PH. Although Cox regression often yielded satisfactory performance, we showed the conditions under which machine and deep learning models can perform better. Indeed, the performance of these methods has often been underestimated due to the improper use of Harrell's concordance index (C-index) instead of more appropriate scores such as Antolini's concordance index, which generalizes C-index in cases where the PH assumption does not hold. In addition, since occasionally high C-index models happen to be badly calibrated, combining Antolini's C-index with Brier's score is useful to assess the overall performance of a survival method. Results on our benchmark data showed that survival prediction should be approached by testing different methods to select the most appropriate one according to sample size, non-linearity and non-PH conditions. To allow an easy reproducibility of these tests on our benchmark data, code and documentation are freely available at https://github.com/compbiomed-unito/survhive.

We argue that many survival analysis and time-to-event models are incorrectly evaluated. First, we survey many examples of evaluation approaches in the literature and find that most rely on concordance (C-index). However, the C-index only measures a model's discriminative ability and does not assess other important aspects, such as the accuracy of the time-to-event predictions or the calibration of the model's probabilistic estimates. Next, we present a set of key desiderata for choosing the right evaluation metric and discuss their pros and cons. These are tailored to the challenges in survival analysis, such as sensitivity to miscalibration and various censoring assumptions. We hypothesize that the current development of survival metrics conforms to a double-helix ladder, and that model validity and metric validity must stand on the same rung of the assumption ladder. Finally, we discuss the appropriate methods for evaluating a survival model in practice and summarize various viewpoints opposing our analysis.

Conventional survival metrics, such as Harrell's concordance index and the Brier Score, rely on the independent censoring assumption for valid inference in the presence of right-censored data. However, when instances are censored for reasons related to the event of interest, this assumption no longer holds, as this kind of dependent censoring biases the marginal survival estimates of popular nonparametric estimators. In this paper, we propose three copula-based metrics to evaluate survival models in the presence of dependent censoring, and design a framework to create realistic, semi-synthetic datasets with dependent censoring to facilitate the evaluation of the metrics. Our empirical analyses in synthetic and semi-synthetic datasets show that our metrics can give error estimates that are closer to the true error, mainly in terms of predictive accuracy.

With the rise of medical foundation models and the growing availability of imaging data, scalable pretraining techniques offer a promising way to identify imaging biomarkers predictive of future disease risk. While current self-supervised methods for 3D medical imaging models capture local structural features like organ morphology, they fail to link pixel biomarkers with long-term health outcomes due to a missing context problem. Current approaches lack the temporal context necessary to identify biomarkers correlated with disease progression, as they rely on supervision derived only from images and concurrent text descriptions. To address this, we introduce time-to-event pretraining, a pretraining framework for 3D medical imaging models that leverages large-scale temporal supervision from paired, longitudinal electronic health records (EHRs). Using a dataset of 18,945 CT scans (4.2 million 2D images) and time-to-event distributions across thousands of EHR-derived tasks, our method improves outcome prediction, achieving an average AUROC increase of 23.7% and a 29.4% gain in Harrell's C-index across 8 benchmark tasks. Importantly, these gains are achieved without sacrificing diagnostic classification performance. This study lays the foundation for integrating longitudinal EHR and 3D imaging data to advance clinical risk prediction.

This work presents the first large-scale neutral benchmark experiment focused on single-event, right-censored, low-dimensional survival data. Benchmark experiments are essential in methodological research to scientifically compare new and existing model classes through proper empirical evaluation. Existing benchmarks in the survival literature are often narrow in scope, focusing, for example, on high-dimensional data. Additionally, they may lack appropriate tuning or evaluation procedures, or are qualitative reviews, rather than quantitative comparisons. This comprehensive study aims to fill the gap by neutrally evaluating a broad range of methods and providing generalizable conclusions. We benchmark 18 models, ranging from classical statistical approaches to many common machine learning methods, on 32 publicly available datasets. The benchmark tunes for both a discrimination measure and a proper scoring rule to assess performance in different settings. Evaluating on 8 survival metrics, we assess discrimination, calibration, and overall predictive performance of the tested models. Using discrimination measures, we find that no method significantly outperforms the Cox model. However, (tuned) Accelerated Failure Time models were able to achieve significantly better results with respect to overall predictive performance as measured by the right-censored log-likelihood. Machine learning methods that performed comparably well include Oblique Random Survival Forests under discrimination, and Cox-based likelihood-boosting under overall predictive performance. We conclude that for predictive purposes in the standard survival analysis setting of low-dimensional, right-censored data, the Cox Proportional Hazards model remains a simple and robust method, sufficient for practitioners.

Survival analysis studies and predicts the time of death, or other singular unrepeated events, based on historical data, while the true time of death for some instances is unknown. Survival trees enable the discovery of complex nonlinear relations in a compact human comprehensible model, by recursively splitting the population and predicting a distinct survival distribution in each leaf node. We use dynamic programming to provide the first survival tree method with optimality guarantees, enabling the assessment of the optimality gap of heuristics. We improve the scalability of our method through a special algorithm for computing trees up to depth two. The experiments show that our method's run time even outperforms some heuristics for realistic cases while obtaining similar out-of-sample performance with the state-of-the-art.

Background: Accurate survival time estimates aid end-of-life medical decision-making. Objectives: Develop an interpretable survival model for elderly residential aged care residents using advanced machine learning. Setting: A major Australasian residential aged care provider. Participants: Residents aged 65+ admitted for long-term care from July 2017 to August 2023. Sample size: 11,944 residents across 40 facilities. Predictors: Factors include age, gender, health status, co-morbidities, cognitive function, mood, nutrition, mobility, smoking, sleep, skin integrity, and continence. Outcome: Probability of survival post-admission, specifically calibrated for 6-month survival estimates. Statistical Analysis: Tested CoxPH, EN, RR, Lasso, GB, XGB, and RF models in 20 experiments with a 90/10 train/test split. Evaluated accuracy using C-index, Harrell's C-index, dynamic AUROC, IBS, and calibrated ROC. Chose XGB for its performance and calibrated it for 1, 3, 6, and 12-month predictions using Platt scaling. Employed SHAP values to analyze predictor impacts. Results: GB, XGB, and RF models showed the highest C-Index values (0.714, 0.712, 0.712). The optimal XGB model demonstrated a 6-month survival prediction AUROC of 0.746 (95% CI 0.744-0.749). Key mortality predictors include age, male gender, mobility, health status, pressure ulcer risk, and appetite. Conclusions: The study successfully applies machine learning to create a survival model for aged care, aligning with clinical insights on mortality risk factors and enhancing model interpretability and clinical utility through explainable AI.