Integrating relative survival in multi-state models-a non-parametric approach.
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ABSTRACT:
SUBMITTER: Manevski D
PROVIDER: S-EPMC9245158 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:For estimating conditional survival functions, non-parametric estimators can be preferred to parametric and semi-parametric estimators due to relaxed assumptions that enable robust estimation. Yet, even when misspecified, parametric and semi-parametric estimators can possess better operating characteristics in small sample sizes due to smaller variance than non-parametric estimators. Fundamentally, this is a bias-variance trade-off situation in that the sample size is not large enough to take advantage of the low bias of non-parametric estimation. Stacked survival models estimate an optimally weighted combination of models that can span parametric, semi-parametric, and non-parametric models by minimizing prediction error. An extensive simulation study demonstrates that stacked survival models consistently perform well across a wide range of scenarios by adaptively balancing the strengths and weaknesses of individual candidate survival models. In addition, stacked survival models perform as well as or better than the model selected through cross-validation. Finally, stacked survival models are applied to a well-known German breast cancer study.
| S-EPMC5963472 | biostudies-literature
Project description:BACKGROUND:Within cancer care, dynamic evaluations of the loss in expectation of life provides useful information to patients as well as physicians. The loss of lifetime function yields the conditional loss in expectation of life given survival up to a specific time point. Due to the inevitable censoring in time-to-event data, loss of lifetime estimation requires extrapolation of both the patient and general population survival function. In this context, the accuracy of different extrapolation approaches has not previously been evaluated. METHODS:The loss of lifetime function was computed by decomposing the all-cause survival function using the relative and general population survival function. To allow extrapolation, the relative survival function was fitted using existing parametric relative survival models. In addition, we introduced a novel mixture cure model suitable for extrapolation. The accuracy of the estimated loss of lifetime function using various extrapolation approaches was assessed in a simulation study and by data from the Danish Cancer Registry where complete follow-up was available. In addition, we illustrated the proposed methodology by analyzing recent data from the Danish Lymphoma Registry. RESULTS:No uniformly superior extrapolation method was found, but flexible parametric mixture cure models and flexible parametric relative survival models seemed to be suitable in various scenarios. CONCLUSION:Using extrapolation to estimate the loss of lifetime function requires careful consideration of the relative survival function outside the available follow-up period. We propose extensive sensitivity analyses when estimating the loss of lifetime function.
| S-EPMC6350283 | biostudies-literature
Project description:BackgroundIn health technology assessment, restricted mean survival time and life expectancy are commonly evaluated. Parametric models are typically used for extrapolation. Spline models using a relative survival framework have been shown to estimate life expectancy of cancer patients more reliably; however, more research is needed to assess spline models using an all-cause survival framework and standard parametric models using a relative survival framework.AimTo assess survival extrapolation using standard parametric models and spline models within relative survival and all-cause survival frameworks.MethodsFrom the Swedish Cancer Registry, we identified patients diagnosed with 5 types of cancer (colon, breast, melanoma, prostate, and chronic myeloid leukemia) between 1981 and 1990 with follow-up until 2020. Patients were categorized into 15 cancer cohorts by cancer and age group (18-59, 60-69, and 70-99 y). We right-censored the follow-up at 2, 3, 5, and 10 y and fitted the parametric models within an all-cause and a relative survival framework to extrapolate to 10 y and lifetime in comparison with the observed Kaplan-Meier survival estimates. All cohorts were modeled with 6 standard parametric models (exponential, Weibull, Gompertz, log-logistic, log-normal, and generalized gamma) and 3 spline models (on hazard, odds, and normal scales).ResultsFor predicting 10-y survival, spline models generally performed better than standard parametric models. However, using an all-cause or a relative survival framework did not show any distinct difference. For lifetime survival, extrapolating from a relative survival framework agreed better with the observed survival, particularly using spline models.ConclusionsFor extrapolation to 10 y, we recommend spline models. For extrapolation to lifetime, we suggest extrapolating in a relative survival framework, especially using spline models.HighlightsFor survival extrapolation to 10 y, spline models generally performed better than standard parametric models did. However, using an all-cause or a relative survival framework showed no distinct difference under the same parametric model.Survival extrapolation to lifetime within a relative survival framework agreed well with the observed data, especially using spline models.Extrapolating parametric models within an all-cause survival framework may overestimate survival proportions at lifetime; models for the relative survival approach may underestimate instead.
| S-EPMC10988990 | biostudies-literature
Project description:Multi-parametric liquid biopsy approach
| PRJEB39331 | ENA
Project description:Multi-state models can be viewed as generalizations of both the standard and competing risks models for survival data. Models for multi-state data have been the theme of many recent published works. Motivated by bone marrow transplant data, we propose a Bayesian model using the gap times between two successive events in a path of events experienced by a subject. Path specific frailties are introduced to capture the dependence structure of the gap times in the paths with two or more states. Under improper prior distributions for the parameters, we establish propriety of the posterior distribution. An efficient Gibbs sampling algorithm is developed for drawing samples from the posterior distribution. An extensive simulation study is carried out to examine the empirical performance of the proposed approach. A bone marrow transplant data set is analyzed in detail to further demonstrate the proposed methodology.
| S-EPMC4567543 | biostudies-literature
Project description:BackgroundEvidence-based treatment decisions in medicine are made founded on population-level evidence obtained during randomized clinical trials. In an era of personalized medicine, these decisions should be based on the predicted benefit of a treatment on a patient-level. Survival prediction models play a central role as they incorporate the time-to-event and censoring. In medical applications uncertainty is critical especially when treatments differ in their side effect profiles or costs. Additionally, models must be adapted to local populations without diminishing performance and often without the original training data available due to privacy concern. Both points are supported by Bayesian models-yet they are rarely used. The aim of this work is to evaluate Bayesian parametric survival models on public datasets including cardiology, infectious diseases, and oncology.Materials and methodsBayesian parametric survival models based on the Exponential and Weibull distribution were implemented as a Python package. A linear combination and a neural network were used for predicting the parameters of the distributions. A superiority design was used to assess whether Bayesian models are better than commonly used models such as Cox Proportional Hazards, Random Survival Forest, and Neural Network-based Cox Proportional Hazards. In a secondary analysis, overfitting was compared between these models. An equivalence design was used to assess whether the prediction performance of Bayesian models after model updating using Bayes rule is equivalent to retraining on the full dataset.ResultsIn this study, we found that Bayesian parametric survival models perform as good as state-of-the art models while requiring less hyperparameters to be tuned and providing a measure of the uncertainty of the predictions. In addition, these models were less prone to overfitting. Furthermore, we show that updating these models using Bayes rule yields equivalent performance compared to models trained on combined original and new datasets.ConclusionsBayesian parametric survival models are non-inferior to conventional survival models while requiring less hyperparameter tuning, being less prone to overfitting, and allowing model updating using Bayes rule. Further, the Bayesian models provide a measure of the uncertainty on the statistical inference, and, in particular, on the prediction.
| S-EPMC10605790 | biostudies-literature
Project description:BackgroundIn decision modeling with time-to-event data, there are a variety of parametric models that can be used to extrapolate the survival function. Each model implies a different hazard function, and in situations in which there is moderate censoring, this can result in quite different survival projections. External information such as expert opinion on long-term survival can more accurately characterize the uncertainty in these extrapolations.ObjectiveWe present a general and easily implementable approach to incorporate various types of expert opinions into parametric survival models, focusing on opinions about survival at various landmark time points.MethodsExpert opinion is incorporated into parametric survival models using Bayesian and frequentist approaches. In the Bayesian method, expert opinion is included through a loss function and in the frequentist approach by penalizing the likelihood function, although in both cases the core approach is the same. The issue of aggregating multiple expert opinions is also considered.ResultsWe apply this method to data from a leukemia trial and use previously elicited expert opinion on survival probabilities for that particular trial population at years 4 and 5 to inform our analysis. We take a robust approach to modeling expert opinion by using pooled distributions and fit a broad class of parametric models to the data. We also assess statistical goodness of fit of the models to both the observed data and expert opinion.ConclusionsExpert opinions can be implemented in a straightforward manner using this novel approach; however, more work is required on the correct elicitation of these quantities.HighlightsPresentation of a novel and open-source method to incorporate expert opinion into decision modeling.Extends upon earlier work in that expert opinion can be incorporated into a wide range of parametric models.Provides methodological guidance for directly including expert opinion in decision modeling, which is a research focus area in NICE TSD 21.1.
| S-EPMC10021125 | biostudies-literature
Project description:BackgroundThe extended illness-death model is a useful tool to study the risks and consequences of hospital-acquired infections (HAIs). The statistical quantities of interest are the transition-specific hazard rates and the transition probabilities as well as attributable mortality (AM) and the population-attributable fraction (PAF). In the most general case calculation of these expressions is mathematically complex.MethodsWhen assuming time-constant hazards calculation of the quantities of interest is facilitated. In this situation the transition probabilities can be expressed in closed mathematical forms. The estimators for AM and PAF can be easily derived from these forms.ResultsIn this paper, we show how to explicitly calculate all the transition probabilities of an extended-illness model with constant hazards. Using a parametric model to estimate the time-constant transition specific hazard rates of a data example, the transition probabilities, AM and PAF can be directly calculated. With a publicly available data example, we show how the approach provides first insights into principle time-dynamics and data structure.ConclusionAssuming constant hazards facilitates the understanding of multi-state processes. Even in a non-constant hazards setting, the approach is a helpful first step for a comprehensive investigation of complex data.
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Project description:The ever-increasing availability of transcriptomic and metabolomic data can be used to deeply analyze and make ever-expanding predictions about biological processes, as changes in the reaction fluxes through genome-wide pathways can now be tracked. Currently, constraint-based metabolic modeling approaches, such as flux balance analysis (FBA), can quantify metabolic fluxes and make steady-state flux predictions on a genome-wide scale using optimization principles. However, relating the differential gene expression or differential metabolite abundances in different physiological states to the differential flux profiles remains a challenge. Here we present a novel method, named REMI (Relative Expression and Metabolomic Integrations), that employs genome-scale metabolic models (GEMs) to translate differential gene expression and metabolite abundance data obtained through genetic or environmental perturbations into differential fluxes to analyze the altered physiology for any given pair of conditions. REMI allows for gene-expression, metabolite abundance, and thermodynamic data to be integrated into a single framework, then uses optimization principles to maximize the consistency between the differential gene-expression levels and metabolite abundance data and the estimated differential fluxes and thermodynamic constraints. We applied REMI to integrate into the Escherichia coli GEM publicly available sets of expression and metabolomic data obtained from two independent studies and under wide-ranging conditions. The differential flux distributions obtained from REMI corresponding to the various perturbations better agreed with the measured fluxomic data, and thus better reflected the different physiological states, than a traditional model. Compared to the similar alternative method that provides one solution from the solution space, REMI was able to enumerate several alternative flux profiles using a mixed-integer linear programming approach. Using this important advantage, we performed a high-frequency analysis of common genes and their associated reactions in the obtained alternative solutions and identified the most commonly regulated genes across any two given conditions. We illustrate that this new implementation provides more robust and biologically relevant results for a better understanding of the system physiology.
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Project description:Genomic prediction models are often calibrated using multi-generation data. Over time, as data accumulates, training data sets become increasingly heterogeneous. Differences in allele frequency and linkage disequilibrium patterns between the training and prediction genotypes may limit prediction accuracy. This leads to the question of whether all available data or a subset of it should be used to calibrate genomic prediction models. Previous research on training set optimization has focused on identifying a subset of the available data that is optimal for a given prediction set. However, this approach does not contemplate the possibility that different training sets may be optimal for different prediction genotypes. To address this problem, we recently introduced a sparse selection index (SSI) that identifies an optimal training set for each individual in a prediction set. Using additive genomic relationships, the SSI can provide increased accuracy relative to genomic-BLUP (GBLUP). Non-parametric genomic models using Gaussian kernels (KBLUP) have, in some cases, yielded higher prediction accuracies than standard additive models. Therefore, here we studied whether combining SSIs and kernel methods could further improve prediction accuracy when training genomic models using multi-generation data. Using four years of doubled haploid maize data from the International Maize and Wheat Improvement Center (CIMMYT), we found that when predicting grain yield the KBLUP outperformed the GBLUP, and that using SSI with additive relationships (GSSI) lead to 5-17% increases in accuracy, relative to the GBLUP. However, differences in prediction accuracy between the KBLUP and the kernel-based SSI were smaller and not always significant.
| S-EPMC8551287 | biostudies-literature