With known cause of death (CoD), competing risk survival methods are applicable in estimating disease-specific survival. Relative survival analysis may be used to estimate disease-specific survival when cause of death is either unknown or subject to misspecification and not reliable for practical usage. This method is popular for population-based cancer survival studies using registry data and does not require CoD information. The standard estimator is the ratio of all-cause survival in the cancer cohort group to the known expected survival from a general reference population. Disease-specific death competes with other causes of mortality, potentially creating dependence among the CoD. The standard ratio estimate is only valid when death from disease and death from other causes are independent. To relax the independence assumption, we formulate dependence using a copula-based model. Likelihood-based parametric method is used to fit the distribution of disease-specific death without CoD information, where the copula is assumed known and the distribution of other cause of mortality is derived from the reference population. We propose a sensitivity analysis, where the analysis is conducted across a range of assumed dependence structures. We demonstrate the utility of our method through simulation studies and an application to French breast cancer data.
Truncation is a statistical phenomenon that occurs in many time to event studies. For example, autopsy-confirmed studies of neurodegenerative diseases are subject to an inherent left and right truncation, also known as double truncation. When the goal is to study the effect of risk factors on survival, the standard Cox regression model cannot be used when the data is subject to truncation. Existing methods which adjust for both left and right truncation in the Cox regression model require independence between the survival times and truncation times, which may not be a reasonable assumption in …
The abundance of modern health data provides many opportunities for the use of machine learning techniques to build better statistical models to improve clinical decision making. Predicting time-to-event distributions, also known as survival analysis, plays a key role in many clinical applications. We introduce a variational time-to-event prediction model, named Variational Survival Inference (VSI), which builds upon recent advances in distribution learning techniques and deep neural networks. VSI addresses the challenges of non-parametric distribution estimation by ($i$) relaxing the restrict…
In survival studies, classical inferences for left-truncated data require quasi-independence, a property that the joint density of truncation time and failure time is factorizable into their marginal densities in the observable region. The quasi-independence hypothesis is testable; many authors have developed tests for left-truncated data with or without right-censoring. In this paper, we propose a class of test statistics for testing the quasi-independence which unifies the existing methods and generates new useful statistics such as conditional Spearman's rank correlation coefficient. Asympt…
We introduce an extension of nonparametric DS inference for arbitrary univariate CDFs to the case in which some failure times are (right)-censored, and then apply this to the problem of assessing evidence regarding assertions about relative risks across two populations. The approach enables exploration of the sensitivity of survival analyses to assumed independence of the missing data process and the failure proces. We present an application to the partially efficacious RV144 (HIV-1) vaccine trial, and show that the strength of conclusions of vaccine efficacy depend on assumptions about the ma…
We consider settings in which the data of interest correspond to pairs of ordered times, e.g, the birth times of the first and second child, the times at which a new user creates an account and makes the first purchase on a website, and the entry and survival times of patients in a clinical trial. In these settings, the two times are not independent (the second occurs after the first), yet it is still of interest to determine whether there exists significant dependence {\em beyond} their ordering in time. We refer to this notion as "quasi-(in)dependence". For instance, in a clinical trial, to …
Longitudinal and survival sub-models are two building blocks for joint modelling of longitudinal and time to event data. Extensive research indicates separate analysis of these two processes could result in biased outputs due to their associations. Conditional independence between measurements of biomarkers and event time process given latent classes or random effects is a common approach for characterising the association between the two sub-models while taking the heterogeneity among the population into account. However, this assumption is tricky to validate because of the unobservable laten…
We introduce a general non-parametric independence test between right-censored survival times and covariates, which may be multivariate. Our test statistic has a dual interpretation, first in terms of the supremum of a potentially infinite collection of weight-indexed log-rank tests, with weight functions belonging to a reproducing kernel Hilbert space (RKHS) of functions; and second, as the norm of the difference of embeddings of certain finite measures into the RKHS, similar to the Hilbert-Schmidt Independence Criterion (HSIC) test-statistic. We study the asymptotic properties of the test, f…
Multi-state survival analysis considers several potential events of interest along a disease pathway. Such analyses are crucial to model complex patient trajectories and are increasingly being used in epidemiological and health economic settings. Multi-state models often make the Markov assumption, whereby an individual's future trajectory is dependent only upon their present state, not their past. In reality, there may be transitional dependence upon either previous events and/or more than one timescale, for example time since entry to the current or previous state(s). The aim of this study w…
Joint modelling of longitudinal and time-to-event data is usually described by a joint model which uses shared or correlated latent effects to capture associations between the two processes. Under this framework, the joint distribution of the two processes can be derived straightforwardly by assuming conditional independence given the random effects. Alternative approaches to induce interdependency into sub-models have also been considered in the literature and one such approach is using copulas to introduce non-linear correlation between the marginal distributions of the longitudinal and time…
Survival analysis is a critical tool for the modelling of time-to-event data, such as life expectancy after a cancer diagnosis or optimal maintenance scheduling for complex machinery. However, current neural network models provide an imperfect solution for survival analysis as they either restrict the shape of the target probability distribution or restrict the estimation to pre-determined times. As a consequence, current survival neural networks lack the ability to estimate a generic function without prior knowledge of its structure. In this article, we present the metaparametric neural netwo…
Most papers implicitly assume competing risks to be induced by residual cohort heterogeneity, i.e. heterogeneity that is not captured by the recorded covariates. Based on this observation we develop a generic statistical description of competing risks that unifies the main schools of thought. Assuming heterogeneity-induced competing risks is much weaker than assuming risk independence. However, we show that it still imposes sufficient constraints to solve the competing risk problem, and derive exact formulae for decontaminated primary risk hazard rates and cause-specific survival functions. Th…
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…
Flexible Estimation of the Heterogeneous Non-Parametric Component in a Relative Survival Cure Model
Sapienza Università di Roma（罗马大学）；Istituto Superiore di Sanità（高等卫生研究所）；Fondazione IRCCS Istituto Nazionale dei Tumori（意大利国家肿瘤研究所基金会IRCCS）；Università della Calabria（卡拉布里亚大学）；Karolinska Institutet（卡罗林斯卡学院）
Joint models initially dedicated to a single longitudinal marker and a single time-to-event need to be extended to account for the rich longitudinal data of cohort studies. Multiple causes of clinical progression are indeed usually observed, and multiple longitudinal markers are collected when the true latent trait of interest is hard to capture (e.g. quality of life, functional dependency, cognitive level). These multivariate and longitudinal data also usually have nonstandard distributions (discrete, asymmetric, bounded,...). We propose a joint model based on a latent process and latent clas…
