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      Multilevel mixed-effects parametric survival analysis: Estimation, simulation, and application

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      The Stata Journal: Promoting communications on statistics and Stata
      SAGE Publications

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          Abstract

          In this article, I present the community-contributed stmixed command for fitting multilevel survival models. It serves as both an alternative to Stata’s official mestreg command and a complimentary command with substantial extensions. stmixed can fit multilevel survival models with any number of levels and random effects at each level, including flexible spline-based approaches (such as Royston–Parmar and the log-hazard equivalent) and user-defined hazard models. Simple or complex time-dependent effects can be included, as can expected mortality for a relative survival model. Left-truncation (delayed entry) is supported, and t-distributed random effects are provided as an alternative to Gaussian random effects. I illustrate the methods with a commonly used dataset of patients with kidney disease suffering recurrent infections and a simulated example illustrating a simple approach to simulating clustered survival data using survsim (Crowther and Lambert 2012, Stata Journal 12: 674–687; 2013, Statistics in Medicine 32: 4118–4134). stmixed is part of the merlin family (Crowther 2017, arXiv Working Paper No. arXiv:1710.02223; 2018, arXiv Working Paper No. arXiv:1806.01615).

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          Most cited references7

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          Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes.

          Differences across studies in terms of design features and methodology, clinical procedures, and patient characteristics, are factors that can contribute to variability in the treatment effect between studies in a meta-analysis (statistical heterogeneity). Regression modelling can be used to examine relationships between treatment effect and covariates with the aim of explaining the variability in terms of clinical, methodological, or other factors. Such an investigation can be undertaken using aggregate data or individual patient data. An aggregate data approach can be problematic as sufficient data are rarely available and translating aggregate effects to individual patients can often be misleading. An individual patient data approach, although usually more resource demanding, allows a more thorough investigation of potential sources of heterogeneity and enables a fuller analysis of time to event outcomes in meta-analysis. Hierarchical Cox regression models are used to identify and explore the evidence for heterogeneity in meta-analysis and examine the relationship between covariates and censored failure time data in this context. Alternative formulations of the model are possible and illustrated using individual patient data from a meta-analysis of five randomized controlled trials which compare two drugs for the treatment of epilepsy. The models are further applied to simulated data examples in which the degree of heterogeneity and magnitude of treatment effect are varied. The behaviour of each model in each situation is explored and compared. Copyright 2005 John Wiley & Sons, Ltd.
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            Regression with frailty in survival analysis.

            In studies of survival, the hazard function for each individual may depend on observed risk variables but usually not all such variables are known or measurable. This unknown factor of the hazard function is usually termed the individual heterogeneity or frailty. When survival is time to the occurrence of a particular type of event and more than one such time may be obtained for each individual, frailty is a common factor among such recurrence times. A model including frailty is fitted to such repeated measures of recurrence times.
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              Simulating biologically plausible complex survival data.

              Simulation studies are conducted to assess the performance of current and novel statistical models in pre-defined scenarios. It is often desirable that chosen simulation scenarios accurately reflect a biologically plausible underlying distribution. This is particularly important in the framework of survival analysis, where simulated distributions are chosen for both the event time and the censoring time. This paper develops methods for using complex distributions when generating survival times to assess methods in practice. We describe a general algorithm involving numerical integration and root-finding techniques to generate survival times from a variety of complex parametric distributions, incorporating any combination of time-dependent effects, time-varying covariates, delayed entry, random effects and covariates measured with error. User-friendly Stata software is provided. Copyright © 2013 John Wiley & Sons, Ltd.

                Author and article information

                Journal
                The Stata Journal: Promoting communications on statistics and Stata
                The Stata Journal
                SAGE Publications
                1536-867X
                1536-8734
                December 2019
                December 18 2019
                December 2019
                : 19
                : 4
                : 931-949
                Affiliations
                [1 ]University of Leicester, Leicester, UK,
                Article
                10.1177/1536867X19893639
                24789760
                a5ba6e91-f68c-4240-9ae6-b66f2d4c47fe
                © 2019

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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