We propose a reinforcement learning method for estimating an optimal dynamic treatment regime for survival outcomes with dependent censoring. The estimator allows the failure time to be conditionally independent of censoring and dependent on the treatment decision times, supports a flexible number of treatment arms and treatment stages, and can maximize either the mean survival time or the survival probability at a certain time point. The estimator is constructed using generalized random survival forests and can have polynomial rates of convergence. Simulations and data analysis results suggest that the new estimator brings higher expected outcomes than existing methods in various settings. An R package dtrSurv is available on CRAN.
This manuscripts develops a new class of deep learning algorithms for outcomes that are potentially censored. To account for censoring, the unobservable loss function used in the absence of censoring is replaced by a censoring unbiased transformation. The resulting class of algorithms can be used to estimate both survival probabilities and restricted mean survival. We show how the deep learning algorithms can be implemented using software for uncensored data using a form of response transformation. Simulations and analysis of the Netherlands 70 Gene Signature Data show strong performance of th…
Kaplan-Meier survival analysis represents the most objective measure of treatment efficacy in oncology, though subjected to potential bias, which is worrisome in an era of precision medicine. Independent of the bias inherent to the design and execution of clinical trials, bias may be the result of patient censoring, or incomplete observation. Unlike disease/progression free survival, overall survival is based on a well defined time point and thus avoids interval censoring, but right-censoring, due to incomplete follow-up, may still be a source of bias. We study three mechanisms of right-censor…
Fiducial Inference, introduced by Fisher in the 1930s, has a long history, which at times aroused passionate disagreements. However, its application has been largely confined to relatively simple parametric problems. In this paper, we present what might be the first time fiducial inference, as generalized by Hannig et al. (2016), is systematically applied to estimation of a nonparametric survival function under right censoring. We find that the resulting fiducial distribution gives rise to surprisingly good statistical procedures applicable to both one sample and two sample problems. In partic…
Censored survival data are common in clinical trial studies. We propose a unified framework for sensitivity analysis to censoring at random in survival data using multiple imputation and martingale, called SMIM. The proposed framework adopts the δ-adjusted and control-based models, indexed by the sensitivity parameter, entailing censoring at random and a wide collection of censoring not at random assumptions. Also, it targets for a broad class of treatment effect estimands defined as functionals of treatment-specific survival functions, taking into account of missing data due to censoring. Mul…
Factorial analyses offer a powerful nonparametric means to detect main or interaction effects among multiple treatments. For survival outcomes, e.g. from clinical trials, such techniques can be adopted for comparing reasonable quantifications of treatment effects. The key difficulty to solve in survival analysis concerns the proper handling of censoring. So far, all existing factorial analyses for survival data were developed under the independent censoring assumption, which is too strong for many applications. As a solution, the central aim of this article is to develop new methods in factori…
In this paper, we propose two variable selection methods for adjusting the censoring information for survival times, such as the restricted mean survival time. To adjust for the influence of censoring, we consider an inverse survival probability weighting (ISPW) for subjects with events. We derive a least absolute shrinkage and selection operator (lasso)-type variable selection method, which considers an inverse weighting for of the squared losses, and an information criterion-type variable selection method, which applies an inverse weighting of the survival probability to the power of each de…
For studying or reducing the bias of functionals of the Kaplan-Meier survival estimator, the jackknifing approach of Stute and Wang (1994) is natural. We have studied the behavior of the jackknife estimate of bias under different configurations of the censoring level, sample size, and the censoring and survival time distributions. The empirical research reveals some new findings about robust calculation of the bias, particularly for higher censoring levels. We have extended their jackknifing approach to cover the case where the largest observation is censored, using the imputation methods for …
Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the "difference" and "product" methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two meth…
The analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. As the censoring mechanism is usually unknown, analyses typically employ the assumption of non-informative censoring. While this assumption usually becomes more plausible as more baseline covariates are being adjusted for, such adjustment also raises concerns. Pre-specification of which covariates will be adjusted for (and how) is difficult, thus prompting the use of data-driven variable selection procedures, which may impede valid inferences to be drawn. The adjustment for cova…
High-dimensional sparse modeling with censored survival data is of great practical importance, and several methods have been proposed for variable selection based on different models. However, the impact of biased sample caused by left-truncation and covariates measurement error to variable selection is not fully explored. In this paper, we mainly focus on the additive hazards model and analyze the high-dimensional survival data subject to left-truncation and measurement error in covariates. We develop the three-stage procedure to correct the error effect, select variables, and estimate the pa…
Benchmarking is commonly used in many healthcare settings to monitor clinical performance, with the aim of increasing cost-effectiveness and safe care of patients. The funnel plot is a popular tool in visualizing the performance of a healthcare center in relation to other centers and to a target, taking into account statistical uncertainty. In this paper we develop methodology for constructing funnel plots for survival data. The method takes into account censoring and can deal with differences in censoring distributions across centers. Practical issues in implementing the methodology are discu…
Methods for the evaluation of the predictive accuracy of biomarkers with respect to survival outcomes subject to right censoring have been discussed extensively in the literature. In cancer and other diseases, survival outcomes are commonly subject to interval censoring by design or due to the follow up schema. In this paper, we present an estimator for the area under the time-dependent receiver operating characteristic ROC curve for interval censored data based on a nonparametric sieve maximum likelihood approach. We establish the asymptotic properties of the proposed estimator, and illustrat…
Instrumental variable (IV) methods allow us the opportunity to address unmeasured confounding in causal inference. However, most IV methods are only applicable to discrete or continuous outcomes with very few IV methods for censored survival outcomes. In this work we propose nonparametric estimators for the local average treatment effect on survival probabilities under both nonignorable and ignorable censoring. We provide an efficient influence function-based estimator and a simple estimation procedure when the IV is either binary or continuous. The proposed estimators possess double-robustnes…
We introduce a self-censoring model for multivariate nonignorable nonmonotone missing data, where the missingness process of each outcome is affected by its own value and is associated with missingness indicators of other outcomes, while conditionally independent of the other outcomes. The self-censoring model complements previous graphical approaches for the analysis of multivariate nonignorable missing data. It is identified under a completeness condition stating that any variability in one outcome can be captured by variability in the other outcomes among complete cases. For estimation, we …
This paper introduces new effect parameters for factorial survival designs with possibly right-censored time-to-event data. In the special case of a two-sample design it coincides with the concordance or Wilcoxon parameter in survival analysis. More generally, the new parameters describe treatment or interaction effects and we develop estimates and tests to infer their presence. We rigorously study the asymptotic properties by means of empirical process techniques and additionally suggest wild bootstrapping for a consistent and distribution-free application of the inference procedures. The sma…
Interval-censored data, in which the event time is only known to lie in some time interval, arise commonly in practice; for example, in a medical study in which patients visit clinics or hospitals at pre-scheduled times, and the events of interest occur between visits. Such data are appropriately analyzed using methods that account for this uncertainty in event time measurement. In this paper we propose a survival tree method for interval-censored data based on the conditional inference framework. Using Monte Carlo simulations we find that the tree is effective in uncovering underlying tree st…
Comparative effectiveness research often involves evaluating the differences in the risks of an event of interest between two or more treatments using observational data. Often, the post-treatment outcome of interest is whether the event happens within a pre-specified time window, which leads to a binary outcome. One source of bias for estimating the causal treatment effect is the presence of confounders, which are usually controlled using propensity score-based methods. An additional source of bias is right-censoring, which occurs when the information on the outcome of interest is not complet…
We consider nonparametric inference for event time distributions based on current status data. We show that in this scenario conventional mixture priors, including the popular Dirichlet process mixture prior, lead to biologically uninterpretable results as they unnaturally skew the probability mass for the event times toward the extremes of the observed data. Simple assumptions on dependent censoring can fix the problem. We then extend the discussion to bivariate current status data with partial ordering of the two outcomes. In addition to dependent censoring, we also exploit some minimal know…
On the Role of Volterra Integral Equations in Self-Consistent, Product-Limit, Inverse Probability of Censoring Weighted, and Redistribution-to-the-Right Estimators for the Survival Function
Dependent Censoring Based on Geometric Optimization
Université Lumière Lyon 2（里昂第二大学）；Université Lyon 1（里昂第一大学）；ERIC（教育、社会与文化研究中心）；Université de Technologie de Compiègne（贡比涅技术大学）；LMAC（数学与计算力学实验室）；École d’Ingénieur Généraliste ESME（ESME工程师学院）
Win-Ratio Regression for Prioritized Composite Outcomes in Observational Studies: Doubly Robust and Efficient Estimation with Future-Score Correction
University of Florida（佛罗里达大学）；University of California San Diego（加州大学圣地亚哥分校）；Stanford University School of Medicine（斯坦福大学医学院）；University of Rochester Medical Center（罗切斯特大学医学中心）
We investigate the performance of model based bootstrap methods for constructing point-wise confidence intervals around the survival function with interval censored data. We show that bootstrapping from the nonparametric maximum likelihood estimator of the survival function is inconsistent for both the current status and case 2 interval censoring models. A model based smoothed bootstrap procedure is proposed and shown to be consistent. In addition, simulation studies are conducted to illustrate the (in)-consistency of the bootstrap methods. Our conclusions in the interval censoring model would…
The accelerated failure time (AFT) models have proved useful in many contexts, though heavy censoring (as for example in cancer survival) and high dimensionality (as for example in microarray data) cause difficulties for model fitting and model selection. We propose new approaches to variable selection for censored data, based on AFT models optimized using regularized weighted least squares. The regularized technique uses a mixture of L1 and L2 norm penalties under two proposed elastic net type approaches. One is the the adaptive elastic net and the other is weighted elastic net. The approache…
How to select the active variables which have significant impact on the event of interest is a very important and meaningful problem in the statistical analysis of ultrahigh-dimensional data. Sure independent screening procedure has been demonstrated to be an effective method to reduce the dimensionality of data from a large scale to a relatively moderate scale. For censored survival data, the existing screening methods mainly adopt the Kaplan--Meier estimator to handle censoring, which may not perform well for scenarios which have heavy censoring rate. In this article, we propose a model-free…
We present a new estimator of the restricted mean survival time in randomized trials where there is right censoring that may depend on treatment and baseline variables. The proposed estimator leverages prognostic baseline variables to obtain equal or better asymptotic precision compared to traditional estimators. Under regularity conditions and random censoring within strata of treatment and baseline variables, the proposed estimator has the following features: (i) it is interpretable under violations of the proportional hazards assumption; (ii) it is consistent and at least as precise as the …
With the rapid development of new anti-cancer agents which are cytostatic, new endpoints are needed to better measure treatment efficacy in phase II trials. For this purpose, Von Hoff (1998) proposed the growth modulation index (GMI), i.e. the ratio between times to progression or progression-free survival times in two successive treatment lines. An essential task in studies using GMI as an endpoint is to estimate the distribution of GMI. Traditional methods for survival data have been used for estimating the GMI distribution because censoring is common for GMI data. However, we point out that…
In this paper, we consider a novel framework of positive-unlabeled data in which as positive data survival times are observed for subjects who have events during the observation time as positive data and as unlabeled data censoring times are observed but whether the event occurs or not are unknown for some subjects. We consider two cases: (1) when censoring time is observed in positive data, and (2) when it is not observed. For both cases, we developed parametric models, nonparametric models, and machine learning models and the estimation strategies for these models. Simulation studies show th…
