Parametric survival densities from phase-type models

After a brief historical survey of parametric survival models, from actuarial, biomedical, demographical and engineering sources, this paper discusses the persistent reasons why parametric models still play an important role in exploratory statistical research. The phase-type models are advanced as a flexible family of latent-class models with interpretable components. These models are now supported by computational statistical methods that make numerical calculation of likelihoods and statistical estimation of parameters feasible in theory for quite complicated settings. However, consideration of Fisher Information and likelihood-ratio type tests to discriminate between model families indicates that only the simplest phase-type model topologies can be stably estimated in practice, even on rather large datasets. An example of a parametric model with features of mixtures, multiple stages or ‘hits’, and a trapping-state is given to illustrate simple computational tools in R, both on simulated data and on a large SEER 1992–2002 breast-cancer dataset.     

A mover-stayer mixture of Markov chain models for the assessment of dedifferentiation and tumour progression in breast cancer

SUMMARY Malignancy grade is a histological measure of attributes related to a breast tumour's aggressive potential. It is not established whether the grade is an inate characteristic which remains unchanged throughout the tumour's development or whether it evolves as the tumour grows. It is likely that a proportion of tumours have the potential to evolve, and so a statistical method was required to assess this hypothesis and, if possible, to estimate the proportion with the potential for evolution. Therefore, a mover-stayer mixture of Markov chain models was developed, with the complication that 'movers' were unobservable because tumours were excised on diagnosis. A quasi-likelihood method was used for estimation. The methods are demonstrated using data from the Swedish twocounty trial of breast-cancer screening.     

A comparison of parametric and semi-parametric survival models with artificial neural networks

Survival models are used to examine data in the event of an occurrence. These are discussed in various types including parametric, non-parametric and semi-parametric models. Parametric models require a clear distribution of survival time, and semi-parametric models assume proportional hazards. Among these models, the non-parametric model of artificial neural network has the fewest assumptions and can be often replaced by other models. Given the importance of distribution Weibull survival models in this study of simulation shape parameter of the Weibull distribution have been assumed as 1, 2 and 3, and also the average rate at levels of 0%–75% have been censored. The values predicted by the neural network forecasting model with parametric survival and Cox regression models were compared. This comparison considering levels of complexity due to the hazard model using the ROC curve and the corresponding tests have been carried out.     

Estimation of sex‐specific survival with uncertainty in sex assessment

In monomorphic species, determination of sex from behavior is prone to errors. The authors develop capture‐recapture survival models that account for uncertainty in the assessment of sex. They examine parameter redundancy for four basic models with constant or time‐dependent survival and encounter probabilities. They further develop a more refined and more appropriate model for an Audouin's gull data set where four distinct behavioral clues have been used. They examine how useful it is to incorporate the least reliable of the clues and the genetic determination of sex available for only a handful of individuals. They finally discuss the implications of their findings for the design of field studies.     

Survival functions for the frailty models based on the discrete compound Poisson process

Frailty models are often used to model heterogeneity in survival analysis. The distribution of the frailty is generally assumed to be continuous. In some circumstances, it is appropriate to consider discrete frailty distributions. Having zero frailty can be interpreted as being immune, and population heterogeneity may be analysed using discrete frailty models. In this paper, survival functions are derived for the frailty models based on the discrete compound Poisson process. Maximum likelihood estimation procedures for the parameters are studied. We examine the fit of the models to earthquake and the traffic accidents’ data sets from Turkey.     

Modeling heteroscedastic age-period-cohort cancer data

The extent to which cancer will be a burden on the Canadian health-care system will be determined by future cancer rates and future population levels in the high-risk age groups. Parametric models of incidence and mortality rates for various cancers may be used to obtain medium-term forecasts of rates, which then can be used in conjunction with population projections to obtain forecasts of total incidence and mortality. Age-period-cohort cancer data often exhibit marked heteroscedasticity, which complicates the modeling of the data. Methods to allow for the effects of this heteroscedasticity on residual processes are developed and discussed in the context of modeling Canadian female breast-cancer incidence data.     

Change point-cure models with application to estimating the change-point effect of age of diagnosis among prostate cancer patients

Previous research on prostate cancer survival trends in the United States National Cancer Institute's Surveillance Epidemiology and End Results database has indicated a potential change-point in the age of diagnosis of prostate cancer around age 50. Identifying a change-point value in prostate cancer survival and cure could have important policy and health care management implications. Statistical analysis of this data has to address two complicating features: (1) change-point models are not smooth functions and so present computational and theoretical difficulties; and (2) models for prostate cancer survival need to account for the fact that many men diagnosed with prostate cancer can be effectively cured of their disease with early treatment. We develop a cure survival model that allows for change-point effects in covariates to investigate a potential change-point in the age of diagnosis of prostate cancer. Our results do not indicate that age under 50 is associated with increased hazard of death from prostate cancer.     

Time-discrete beta-process model for interval-censored survival data

Grouped survival data with possible interval censoring arise in a variety of settings. This paper presents nonparametric Bayes methods for the analysis of such data. The random cumulative hazard, common to every subject, is assumed to be a realization of a Lévy process. A time-discrete beta process, introduced by Hjort, is considered for modeling the prior process. A sampling-based Monte Carlo algorithm is used to find posterior estimates of several quantities of interest. The methodology presented here is used to check further modeling assumptions. Also, the methodology developed in this paper is illustrated with data for the times to cosmetic deterioration of breast-cancer patients. An extension of the methodology is presented to deal with two interval-censored times in tandem data (as with some AIDS incubation data).     

Modelling population-based cancer survival trends using join point models for grouped survival data

Summary.  In the USA cancer as a whole is the second leading cause of death and a major burden to health care; thus medical progress against cancer is a major public health goal. There are many individual studies to suggest that cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of cancer patients. To understand better the relationship between medical improvements and the survival experience for the patient population at large, it is useful to evaluate cancer survival trends on the population level, e.g. to find out when and how much the cancer survival rates changed. We analyse population-based grouped cancer survival data by incorporating join points into the survival models. A join point survival model facilitates the identification of trends with significant change-points in cancer survival, when related to cancer treatments or interventions. The Bayesian information criterion is used to select the number of join points. The performance of the join point survival models is evaluated with respect to cancer prognosis, join point locations, annual percentage changes in death rates by year of diagnosis and sample sizes through intensive simulation studies. The model is then applied to grouped relative survival data for several major cancer sites from the 'Surveillance, epidemiology and end results' programme of the National Cancer Institute. The change-points in the survival trends for several major cancer sites are identified and the potential driving forces behind such change-points are discussed.     

Predictive comparison of joint longitudinal-survival modeling: a case study illustrating competing approaches

The joint modeling of longitudinal and survival data has received extraordinary attention in the statistics literature recently, with models and methods becoming increasingly more complex. Most of these approaches pair a proportional hazards survival with longitudinal trajectory modeling through parametric or nonparametric specifications. In this paper we closely examine one data set previously analyzed using a two parameter parametric model for Mediterranean fruit fly (medfly) egg-laying trajectories paired with accelerated failure time and proportional hazards survival models. We consider parametric and nonparametric versions of these two models, as well as a proportional odds rate model paired with a wide variety of longitudinal trajectory assumptions reflecting the types of analyses seen in the literature. In addition to developing novel nonparametric Bayesian methods for joint models, we emphasize the importance of model selection from among joint and non joint models. The default in the literature is to omit at the outset non joint models from consideration. For the medfly data, a predictive diagnostic criterion suggests that both the choice of survival model and longitudinal assumptions can grossly affect model adequacy and prediction. Specifically for these data, the simple joint model used in by Tseng et al. (Biometrika 92:587–603, 2005) and models with much more flexibility in their longitudinal components are predictively outperformed by simpler analyses. This case study underscores the need for data analysts to compare on the basis of predictive performance different joint models and to include non joint models in the pool of candidates under consideration.     

Disentangling the sources of variation in the survival of the European dipper

The population growth rate of the European dipper has been shown to decrease with winter temperature and population size. We examine here the demographic mechanism for this effect by analysing how these factors affect the survival rate. Using more than 20 years of capture-mark-recapture data (1974-1997) based on more than 4000 marked individuals, we perform analyses using open capture-mark-recapture models. This allowed us to estimate the annual apparent survival rates (probability of surviving and staying on the study site from one year to the next one) and the recapture probabilities. We partitioned the variance of the apparent survival rates into sampling variance and process variance using random effects models, and investigated which variables best accounted for temporal process variation. Adult males and females had similar apparent survival rates, with an average of 0.52 and a coefficient of variation of 40%. Chick apparent survival was lower, averaging 0.06 with a coefficient of variation of 42%. Eighty percent of the variance in apparent survival rates was explained by winter temperature and population size for adults and 48% by winter temperature for chicks. The process variance outweighed the sampling variance both for chick and adult survival rates, which explained that shrunk estimates obtained under random effects models were close to MLE estimates. A large proportion of the annual variation in the apparent survival rate of chicks appears to be explained by inter-year differences in dispersal rates.     

Disentangling the sources of variation in the survival of the European dipper

The population growth rate of the European dipper has been shown to decrease with winter temperature and population size. We examine here the demographic mechanism for this effect by analysing how these factors affect the survival rate. Using more than 20 years of capture-mark-recapture data (1974-1997) based on more than 4000 marked individuals, we perform analyses using open capture-mark-recapture models. This allowed us to estimate the annual apparent survival rates (probability of surviving and staying on the study site from one year to the next one) and the recapture probabilities. We partitioned the variance of the apparent survival rates into sampling variance and process variance using random effects models, and investigated which variables best accounted for temporal process variation. Adult males and females had similar apparent survival rates, with an average of 0.52 and a coefficient of variation of 40%. Chick apparent survival was lower, averaging 0.06 with a coefficient of variation of 42%. Eighty percent of the variance in apparent survival rates was explained by winter temperature and population size for adults and 48% by winter temperature for chicks. The process variance outweighed the sampling variance both for chick and adult survival rates, which explained that shrunk estimates obtained under random effects models were close to MLE estimates. A large proportion of the annual variation in the apparent survival rate of chicks appears to be explained by inter-year differences in dispersal rates.     

Survival estimation and the effects of dependency among animals

Survival models assume that fates of individuals are independent, yet the robustness of this assumption has been poorly quantified. We examine how empirically derived estimates of the variance of survival rates are affected by dependency in survival probability among individuals. We used Monte Carlo simulations to generate known amounts of dependency among pairs of individuals and analyzed these data with Kaplan-Meier and Cormack-Jolly-Seber models. Dependency significantly increased these empirical variances as compared to theoretically derived estimates of variance from the same populations. Using resighting data from 168 pairs of black brant ( Branta bernicla nigricans ), we used a resampling procedure and program RELEASE to estimate empirical and mean theoretical variances. We estimated that the relationship between paired individuals caused the empirical variance of the survival rate to be 155% larger than the empirical variance for unpaired individuals. Monte Carlo simulations and use of this resampling strategy can provide investigators with information on how robust their data are to this common assumption of independent survival probabilities.     

Survival estimation and the effects of dependency among animals

Survival models assume that fates of individuals are independent, yet the robustness of this assumption has been poorly quantified. We examine how empirically derived estimates of the variance of survival rates are affected by dependency in survival probability among individuals. We used Monte Carlo simulations to generate known amounts of dependency among pairs of individuals and analyzed these data with Kaplan-Meier and Cormack-Jolly-Seber models. Dependency significantly increased these empirical variances as compared to theoretically derived estimates of variance from the same populations. Using resighting data from 168 pairs of black brant ( Branta bernicla nigricans ), we used a resampling procedure and program RELEASE to estimate empirical and mean theoretical variances. We estimated that the relationship between paired individuals caused the empirical variance of the survival rate to be 155% larger than the empirical variance for unpaired individuals. Monte Carlo simulations and use of this resampling strategy can provide investigators with information on how robust their data are to this common assumption of independent survival probabilities.     

Bayesian gamma frailty models for survival data with semi-competing risks and treatment switching

Motivated from a colorectal cancer study, we propose a class of frailty semi-competing risks survival models to account for the dependence between disease progression time, survival time, and treatment switching. Properties of the proposed models are examined and an efficient Gibbs sampling algorithm using the collapsed Gibbs technique is developed. A Bayesian procedure for assessing the treatment effect is also proposed. The deviance information criterion (DIC) with an appropriate deviance function and Logarithm of the pseudomarginal likelihood (LPML) are constructed for model comparison. A simulation study is conducted to examine the empirical performance of DIC and LPML and as well as the posterior estimates. The proposed method is further applied to analyze data from a colorectal cancer study.     

Bayesian Spatial Analysis for the Evaluation of Breast Cancer Detection Methods

This study investigated the impact of spatial location on the effectiveness of population‐based breast screening in reducing breast cancer mortality compared to other detection methods among Queensland women. The analysis was based on linked population‐based datasets from BreastScreen Queensland and the Queensland Cancer Registry for the period of 1997–2008 for women aged less than 90 years at diagnosis. A Bayesian hierarchical regression modelling approach was adopted and posterior estimation was performed using Markov Chain Monte Carlo techniques. This approach accommodated sparse data resulting from rare outcomes in small geographic areas, while allowing for spatial correlation and demographic influences to be included. A relative survival model was chosen to evaluate the relative excess risk for each breast cancer related factor. Several models were fitted to examine the influence of demographic information, cancer stage, geographic information and detection method on women's relative survival. Overall, the study demonstrated that including the detection method and geographic information when assessing the relative survival of breast cancer patients helped capture unexplained and spatial variability. The study also found evidence of better survival among women with breast cancer diagnosed in a screening program than those detected otherwise, as well as lower risk for those residing in a more urban or socio‐economically advantaged region, even after adjusting for tumour stage, environmental factors and demographics. However, no evidence of dependency between method of detection and geographic location was found. This project provides a sophisticated approach to examining the benefit of a screening program while considering the influence of geographic factors.     

Bayesian Transformation Models for Multivariate Survival Data

In this paper, we propose a general class of Gamma frailty transformation models for multivariate survival data. The transformation class includes the commonly used proportional hazards and proportional odds models. The proposed class also includes a family of cure rate models. Under an improper prior for the parameters, we establish propriety of the posterior distribution. A novel Gibbs sampling algorithm is developed for sampling from the observed data posterior distribution. A simulation study is conducted to examine the properties of the proposed methodology. An application to a data set from a cord blood transplantation study is also reported.     

Maximum Penalized Likelihood Estimation in a Gamma-Frailty Model

The shared frailty models allow for unobserved heterogeneity or for statistical dependence between observed survival data. The most commonly used estimation procedure in frailty models is the EM algorithm, but this approach yields a discrete estimator of the distribution and consequently does not allow direct estimation of the hazard function. We show how maximum penalized likelihood estimation can be applied to nonparametric estimation of a continuous hazard function in a shared gamma-frailty model with right-censored and left-truncated data. We examine the problem of obtaining variance estimators for regression coefficients, the frailty parameter and baseline hazard functions. Some simulations for the proposed estimation procedure are presented. A prospective cohort (Paquid) with grouped survival data serves to illustrate the method which was used to analyze the relationship between environmental factors and the risk of dementia.     

Bayesian Weibull tree models for survival analysis of clinico-genomic data

An important goal of research involving gene expression data for outcome prediction is to establish the ability of genomic data to define clinically relevant risk factors. Recent studies have demonstrated that microarray data can successfully cluster patients into low- and high-risk categories. However, the need exists for models which examine how genomic predictors interact with existing clinical factors and provide personalized outcome predictions. We have developed clinico-genomic tree models for survival outcomes which use recursive partitioning to subdivide the current data set into homogeneous subgroups of patients, each with a specific Weibull survival distribution. These trees can provide personalized predictive distributions of the probability of survival for individuals of interest. Our strategy is to fit multiple models; within each model we adopt a prior on the Weibull scale parameter and update this prior via Empirical Bayes whenever the sample is split at a given node. The decision to split is based on a Bayes factor criterion. The resulting trees are weighted according to their relative likelihood values and predictions are made by averaging over models. In a pilot study of survival in advanced stage ovarian cancer we demonstrate that clinical and genomic data are complementary sources of information relevant to survival, and we use the exploratory nature of the trees to identify potential genomic biomarkers worthy of further study.     

Effects of neckbands on survival and fidelity of white-fronted and Canada geese captured as non-breeding adults

We conducted an experiment to examine the effect of neckbands, controlling for differences in sex, species and year of study (1991-1997), on probabilities of capture, survival, reporting, and fidelity in non-breeding small Canada ( Branta canadensis hutchinsi ) and white-fronted ( Anser albifrons frontalis ) geese. In Canada's central arctic, we systematically double-marked about half of the individuals from each species with neckbands and legbands, and we marked the other half only with legbands. We considered 48 a priori models that included combinations of sex, species, year, and neckband effects on the four population parameters produced by Burnham's (1993) model, using AIC for model selection. The four best approximating models each included a negative effect of neckbands on survival, and effect size varied among years. True survival probability of neckbanded birds annually ranged from 0.006 to 0.23 and 0.039 to 0.22 (Canada and white-fronted geese, respectively) lower than for conspecifics without neckbands. Changes in estimates of survival probability in neckbanded birds appeared to attenuate more recently, particularly in Canada Geese, a result that we suspect was related to lower retention rates of neckbands. We urge extreme caution in use of neckbands for estimation of certain population parameters, and discourage their use for estimation of unbiased survival probability in these two species.