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      A flexible parametric accelerated failure time model and the extension to time-dependent acceleration factors

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          Summary

          Accelerated failure time (AFT) models are used widely in medical research, though to a much lesser extent than proportional hazards models. In an AFT model, the effect of covariates act to accelerate or decelerate the time to event of interest, that is, shorten or extend the time to event. Commonly used parametric AFT models are limited in the underlying shapes that they can capture. In this article, we propose a general parametric AFT model, and in particular concentrate on using restricted cubic splines to model the baseline to provide substantial flexibility. We then extend the model to accommodate time-dependent acceleration factors. Delayed entry is also allowed, and hence, time-dependent covariates. We evaluate the proposed model through simulation, showing substantial improvements compared to standard parametric AFT models. We also show analytically and through simulations that the AFT models are collapsible, suggesting that this model class will be well suited to causal inference. We illustrate the methods with a data set of patients with breast cancer. Finally, we provide highly efficient, user-friendly Stata, and R software packages.

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          Most cited references34

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          Flexible regression models with cubic splines

          We describe the use of cubic splines in regression models to represent the relationship between the response variable and a vector of covariates. This simple method can help prevent the problems that result from inappropriate linearity assumptions. We compare restricted cubic spline regression to non-parametric procedures for characterizing the relationship between age and survival in the Stanford Heart Transplant data. We also provide an illustrative example in cancer therapeutics.
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            Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects.

            Modelling of censored survival data is almost always done by Cox proportional-hazards regression. However, use of parametric models for such data may have some advantages. For example, non-proportional hazards, a potential difficulty with Cox models, may sometimes be handled in a simple way, and visualization of the hazard function is much easier. Extensions of the Weibull and log-logistic models are proposed in which natural cubic splines are used to smooth the baseline log cumulative hazard and log cumulative odds of failure functions. Further extensions to allow non-proportional effects of some or all of the covariates are introduced. A hypothesis test of the appropriateness of the scale chosen for covariate effects (such as of treatment) is proposed. The new models are applied to two data sets in cancer. The results throw interesting light on the behaviour of both the hazard function and the hazard ratio over time. The tools described here may be a step towards providing greater insight into the natural history of the disease and into possible underlying causes of clinical events. We illustrate these aspects by using the two examples in cancer. Copyright 2002 John Wiley & Sons, Ltd.
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              Survival analysis for economic evaluations alongside clinical trials--extrapolation with patient-level data: inconsistencies, limitations, and a practical guide.

              N Latimer (2013)
              In health technology assessments (HTAs) of interventions that affect survival, it is essential to accurately estimate the survival benefit associated with the new treatment. Generally, trial data must be extrapolated, and many models are available for this purpose. The choice of extrapolation model is critical because different models can lead to very different cost-effectiveness results. A failure to systematically justify the chosen model creates the possibility of bias and inconsistency between HTAs. To demonstrate the limitations and inconsistencies associated with the survival analysis component of HTAs and to propose a process guide that will help exclude these from future analyses. We reviewed the survival analysis component of 45 HTAs undertaken for the National Institute for Health and Clinical Excellence (NICE) in the cancer disease area. We drew upon our findings to identify common limitations and to develop a process guide. The chosen survival models were not systematically justified in any of the HTAs reviewed. The range of models considered was usually insufficient, and the rationale for the chosen model was universally limited: In particular, the plausibility of the extrapolated portion of fitted survival curves was very rarely explicitly considered. Limitations. We do not seek to describe and review all methods available for performing survival analysis-several approaches exist that are not mentioned in this article. Instead we seek to analyze methods commonly used in HTAs and limitations associated with their application. Survival analysis has not been conducted systematically in HTAs. A systematic approach such as the one proposed here is required to reduce the possibility of bias in cost-effectiveness results and inconsistency between technology assessments.
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                Author and article information

                Contributors
                Journal
                Biostatistics
                Biostatistics
                biosts
                Biostatistics (Oxford, England)
                Oxford University Press
                1465-4644
                1468-4357
                July 2023
                26 May 2022
                26 May 2022
                : 24
                : 3
                : 811-831
                Affiliations
                Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Box 281, S-171 77 Stockholm, Sweden
                MRC CTU at UCL , 90 High Holborn, Holborn, London WC1V 6LJ, UK
                Department of Medical Epidemiology and Biostatistics , Karolinska Institutet, Box 281, S-171 77 Stockholm, Sweden
                Author notes
                To whom correspondence should be addressed. michael.crowther@ 123456ki.se
                Author information
                https://orcid.org/0000-0001-8378-8259
                Article
                kxac009
                10.1093/biostatistics/kxac009
                10346080
                35639824
                6d4a88ea-3552-4eb5-b38f-ff4d13b49224
                © The Author 2022. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 February 2021
                : 09 October 2021
                : 14 December 2021
                Page count
                Pages: 21
                Categories
                Article
                AcademicSubjects/SCI01530

                Biostatistics
                accelerated failure time,causal inference,software,survival analysis,time-dependent effects

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