survival curve
Isotonic Survival Regression: Calibrated Survival Distributions from Deep Cox Models
Jain, Anchit, Zhang, Kevin, Bates, Stephen
Time-to-event data is widespread across the life sciences and engineering, but it is typically encountered together with censoring, which complicates the application of standard machine learning methods. Deep Cox models have emerged as a popular method for analyzing time-to-event data because they gracefully handle censoring and can be used with unstructured data such as clinical text reports, genomic sequences, and pathology images. However, their predicted survival probabilities are often poorly calibrated, thus limiting their practical utility. In this paper, we propose a novel post hoc calibration method for Deep Cox models that uses isotonic regression to refine predicted survival probabilities without affecting discriminative power. We establish favorable theoretical guarantees, including a double-robustness property and asymptotic calibration. Experiments on synthetic and real-world clinical data demonstrate the empirical effectiveness of our method.
Causal Fairness for Survival Analysis
In the data-driven era, large-scale datasets are routinely collected and analyzed using machine learning (ML) and artificial intelligence (AI) to inform decisions in high-stakes domains such as healthcare, employment, and criminal justice, raising concerns about the fairness behavior of these systems. Existing works in fair ML cover tasks such as bias detection, fair prediction, and fair decision-making, but largely focus on static settings. At the same time, fairness in temporal contexts, particularly survival/time-to-event (TTE) analysis, remains relatively underexplored, with current approaches to fair survival analysis adopting statistical fairness definitions, which, even with unlimited data, cannot disentangle the causal mechanisms that generate disparities. To address this gap, we develop a causal framework for fairness in TTE analysis, enabling the decomposition of disparities in survival into contributions from direct, indirect, and spurious pathways. This provides a human-understandable explanation of why disparities arise and how they evolve over time. Our non-parametric approach proceeds in four steps: (1) formalizing the necessary assumptions about censoring and lack of confounding using a graphical model; (2) recovering the conditional survival function given covariates; (3) applying the Causal Reduction Theorem to reframe the problem in a form amenable to causal pathway decomposition; (4) estimating the effects efficiently. Finally, our approach is used to analyze the temporal evolution of racial disparities in outcome after admission to an intensive care unit (ICU).
Nonparametric Regression Discontinuity Designs with Survival Outcomes
Schuessler, Maximilian, Sverdrup, Erik, Tibshirani, Robert, Wager, Stefan
Quasi-experimental evaluations are central for generating real-world causal evidence and complementing insights from randomized trials. The regression discontinuity design (RDD) is a quasi-experimental design that can be used to estimate the causal effect of treatments that are assigned based on a running variable crossing a threshold. Such threshold-based rules are ubiquitous in healthcare, where predictive and prognostic biomarkers frequently guide treatment decisions. However, standard RD estimators rely on complete outcome data, an assumption often violated in time-to-event analyses where censoring arises from loss to follow-up. To address this issue, we propose a nonparametric approach that leverages doubly robust censoring corrections and can be paired with existing RD estimators. Our approach can handle multiple survival endpoints, long follow-up times, and covariate-dependent variation in survival and censoring. We discuss the relevance of our approach across multiple areas of applications and demonstrate its usefulness through simulations and the prostate component of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial where our new approach offers several advantages, including higher efficiency and robustness to misspecification. We have also developed an open-source software package, $\texttt{rdsurvival}$, for the $\texttt{R}$ language.
Efficient and Debiased Learning of Average Hazard Under Non-Proportional Hazards
Meng, Xiang, Tian, Lu, Kehl, Kenneth, Uno, Hajime
The hazard ratio from the Cox proportional hazards model is a ubiquitous summary of treatment effect. However, when hazards are non-proportional, the hazard ratio can lose a stable causal interpretation and become study-dependent because it effectively averages time-varying effects with weights determined by follow-up and censoring. We consider the average hazard (AH) as an alternative causal estimand: a population-level person-time event rate that remains well-defined and interpretable without assuming proportional hazards. Although AH can be estimated nonparametrically and regression-style adjustments have been proposed, existing approaches do not provide a general framework for flexible, high-dimensional nuisance estimation with valid sqrt{n} inference. We address this gap by developing a semiparametric, doubly robust framework for covariate-adjusted AH. We establish pathwise differentiability of AH in the nonparametric model, derive its efficient influence function, and construct cross-fitted, debiased estimators that leverage machine learning for nuisance estimation while retaining asymptotically normal, sqrt{n}-consistent inference under mild product-rate conditions. Simulations demonstrate that the proposed estimator achieves small bias and near-nominal confidence-interval coverage across proportional and non-proportional hazards settings, including crossing-hazards regimes where Cox-based summaries can be unstable. We illustrate practical utility in comparative effectiveness research by comparing immunotherapy regimens for advanced melanoma using SEER-Medicare linked data.
Efficient and scalable clustering of survival curves
Villanueva, Nora M., Sestelo, Marta, Meira-Machado, Luis
Survival analysis encompasses a broad range of methods for analyzing time-to-event data, with one key objective being the comparison of survival curves across groups. Traditional approaches for identifying clusters of survival curves often rely on computationally intensive bootstrap techniques to approximate the null hypothesis distribution. While effective, these methods impose significant computational burdens. In this work, we propose a novel approach that leverages the k-means and log-rank test to efficiently identify and cluster survival curves. Our method eliminates the need for computationally expensive resampling, significantly reducing processing time while maintaining statistical reliability. By systematically evaluating survival curves and determining optimal clusters, the proposed method ensures a practical and scalable alternative for large-scale survival data analysis. Through simulation studies, we demonstrate that our approach achieves results comparable to existing bootstrap-based clustering methods while dramatically improving computational efficiency. These findings suggest that the log-rank-based clustering procedure offers a viable and time-efficient solution for researchers working with multiple survival curves in medical and epidemiological studies.
Methodology for Comparing Machine Learning Algorithms for Survival Analysis
Cardoso, Lucas Buk, Angelo, Simone Aldrey, Bonilha, Yasmin Pacheco Gil, Maia, Fernando, Ribeiro, Adeylson Guimarรฃes, Curado, Maria Paula, Fernandes, Gisele Aparecida, Parro, Vanderlei Cunha, Cipparrone, Flรกvio Almeida de Magalhรฃes, Filho, Alexandre Dias Porto Chiavegatto, Filho, Victor Wรผnsch, Toporcov, Tatiana Natasha
This study presents a comparative methodological analysis of six machine learning models for survival analysis (MLSA). Using data from nearly 45,000 colorectal cancer patients in the Hospital-Based Cancer Registries of Sรฃo Paulo, we evaluated Random Survival Forest (RSF), Gradient Boosting for Survival Analysis (GBSA), Survival SVM (SSVM), XGBoost-Cox (XGB-Cox), XGBoost-AFT (XGB-AFT), and LightGBM (LGBM), capable of predicting survival considering censored data. Hyperparameter optimization was performed with different samplers, and model performance was assessed using the Concordance Index (C-Index), C-Index IPCW, time-dependent AUC, and Integrated Brier Score (IBS). Survival curves produced by the models were compared with predictions from classification algorithms, and predictor interpretation was conducted using SHAP and permutation importance. XGB-AFT achieved the best performance (C-Index = 0.7618; IPCW = 0.7532), followed by GBSA and RSF. The results highlight the potential and applicability of MLSA to improve survival prediction and support decision making.
Deep Multi-task Gaussian Processes for Survival Analysis with Competing Risks
Designing optimal treatment plans for patients with comorbidities requires accurate cause-specific mortality prognosis. Motivated by the recent availability of linked electronic health records, we develop a nonparametric Bayesian model for survival analysis with competing risks, which can be used for jointly assessing a patient's risk of multiple (competing) adverse outcomes. The model views a patient's survival times with respect to the competing risks as the outputs of a deep multi-task Gaussian process (DMGP), the inputs to which are the patients' covari-ates. Unlike parametric survival analysis methods based on Cox and Weibull models, our model uses DMGPs to capture complex non-linear interactions between the patients' covariates and cause-specific survival times, thereby learning flexible patient-specific and cause-specific survival curves, all in a data-driven fashion without explicit parametric assumptions on the hazard rates. We propose a varia-tional inference algorithm that is capable of learning the model parameters from time-to-event data while handling right censoring. Experiments on synthetic and real data show that our model outperforms the state-of-the-art survival models.
Learning a Distance for the Clustering of Patients with Amyotrophic Lateral Sclerosis
Tejedor, Guillaume, Peralta, Veronika, Labroche, Nicolas, Marcel, Patrick, Blasco, Hรฉlรจne, Alarcan, Hugo
Amyotrophic lateral sclerosis (ALS) is a severe disease with a typical survival of 3-5 years after symptom onset. Current treatments offer only limited life extension, and the variability in patient responses highlights the need for personalized care. However, research is hindered by small, heterogeneous cohorts, sparse longitudinal data, and the lack of a clear definition for clinically meaningful patient clusters. Existing clustering methods remain limited in both scope and number. To address this, we propose a clustering approach that groups sequences using a disease progression declarative score. Our approach integrates medical expertise through multiple descriptive variables, investigating several distance measures combining such variables, both by reusing off-the-shelf distances and employing a weak-supervised learning method. We pair these distances with clustering methods and benchmark them against state-of-the-art techniques. The evaluation of our approach on a dataset of 353 ALS patients from the University Hospital of Tours, shows that our method outperforms state-of-the-art methods in survival analysis while achieving comparable silhouette scores. In addition, the learned distances enhance the relevance and interpretability of results for medical experts.
PISA: An AI Pipeline for Interpretable-by-design Survival Analysis Providing Multiple Complexity-Accuracy Trade-off Models
Schlender, Thalea, Romme, Catharina J. A., van der Linden, Yvette M., van Lonkhuijzen, Luc R. C. W., Bosman, Peter A. N., Alderliesten, Tanja
Survival analysis is central to clinical research, informing patient prognoses, guiding treatment decisions, and optimising resource allocation. Accurate time-to-event predictions not only improve quality of life but also reveal risk factors that shape clinical practice. For these models to be relevant in healthcare, interpretability is critical: predictions must be traceable to patient-specific characteristics, and risk factors should be identifiable to generate actionable insights for both clinicians and researchers. Traditional survival models often fail to capture non-linear interactions, while modern deep learning approaches, though powerful, are limited by poor interpretability. We propose a Pipeline for Interpretable Survival Analysis (PISA) - a pipeline that provides multiple survival analysis models that trade off complexity and performance. Using multiple-feature, multi-objective feature engineering, PISA transforms patient characteristics and time-to-event data into multiple survival analysis models, providing valuable insights into the survival prediction task. Crucially, every model is converted into simple patient stratification flowcharts supported by Kaplan-Meier curves, whilst not compromising on performance. While PISA is model-agnostic, we illustrate its flexibility through applications of Cox regression and shallow survival trees, the latter avoiding proportional hazards assumptions. Applied to two clinical benchmark datasets, PISA produced interpretable survival models and intuitive stratification flowcharts whilst achieving state-of-the-art performances. Revisiting a prior departmental study further demonstrated its capacity to automate survival analysis workflows in real-world clinical research.
KM-GPT: An Automated Pipeline for Reconstructing Individual Patient Data from Kaplan-Meier Plots
Zhao, Yao, Sun, Haoyue, Ding, Yantian, Xu, Yanxun
Reconstructing individual patient data (IPD) from Kaplan-Meier (KM) plots provides valuable insights for evidence synthesis in clinical research. However, existing approaches often rely on manual digitization, which is error-prone and lacks scalability. To address these limitations, we develop KM-GPT, the first fully automated, AI-powered pipeline for reconstructing IPD directly from KM plots with high accuracy, robustness, and reproducibility. KM-GPT integrates advanced image preprocessing, multi-modal reasoning powered by GPT-5, and iterative reconstruction algorithms to generate high-quality IPD without manual input or intervention. Its hybrid reasoning architecture automates the conversion of unstructured information into structured data flows and validates data extraction from complex KM plots. To improve accessibility, KM-GPT is equipped with a user-friendly web interface and an integrated AI assistant, enabling researchers to reconstruct IPD without requiring programming expertise. KM-GPT was rigorously evaluated on synthetic and real-world datasets, consistently demonstrating superior accuracy. To illustrate its utility, we applied KM-GPT to a meta-analysis of gastric cancer immunotherapy trials, reconstructing IPD to facilitate evidence synthesis and biomarker-based subgroup analyses. By automating traditionally manual processes and providing a scalable, web-based solution, KM-GPT transforms clinical research by leveraging reconstructed IPD to enable more informed downstream analyses, supporting evidence-based decision-making.