Semi‐parametric accelerated failure‐time model: A useful alternative to the proportional‐hazards model in cancer clinical trials

2021 ◽  
Author(s):  
Tomasz Burzykowski
2021 ◽  
pp. 096228022110417
Author(s):  
Menglan Pang ◽  
Robert W Platt ◽  
Tibor Schuster ◽  
Michal Abrahamowicz

The accelerated failure time model is an alternative to the Cox proportional hazards model in survival analysis. However, conclusions regarding the associations of prognostic factors with event times are valid only if the underlying modeling assumptions are met. In contrast to several flexible methods for relaxing the proportional hazards and linearity assumptions in the Cox model, formal investigation of the constant-over-time time ratio and linearity assumptions in the accelerated failure time model has been limited. Yet, in practice, prognostic factors may have time-dependent and/or nonlinear effects. Furthermore, parametric accelerated failure time models require correct specification of the baseline hazard function, which is treated as a nuisance parameter in the Cox proportional hazards model, and is rarely known in practice. To address these challenges, we propose a flexible extension of the accelerated failure time model where unpenalized regression B-splines are used to model (i) the baseline hazard function of arbitrary shape, (ii) the time-dependent covariate effects on the hazard, and (iii) nonlinear effects for continuous covariates. Simulations evaluate the accuracy of the time-dependent and/or nonlinear estimates, and of the resulting survival functions, in multivariable settings. The proposed flexible extension of the accelerated failure time model is applied to re-assess the effects of prognostic factors on mortality after septic shock.


2004 ◽  
Vol 94 (9) ◽  
pp. 1022-1026 ◽  
Author(s):  
H. Scherm ◽  
P. S. Ojiambo

Data on the occurrence and timing of discrete events such as spore germination, disease onset, or propagule death are recorded commonly in epidemiological studies. When analyzing such “time-to-event” data, survival analysis is superior to conventional statistical techniques because it can accommodate censored observations, i.e., cases in which the event has not occurred by the end of the study. Central to survival analysis are two mathematical functions, the survivor function, which describes the probability that an individual will “survive” (i.e., that the event will not occur) until a given point in time, and the hazard function, which gives the instantaneous risk that the event will occur at that time, given that it has not occurred previously. These functions can be compared among two or more groups using chi-square-based test statistics. The effects of discrete or continuous covariates on survival times can be quantified with two types of models, the accelerated failure time model and the proportional hazards model. When applied to longitudinal data on the timing of defoliation of individual blueberry leaves in the field, analysis with the accelerated failure time model revealed a significantly (P < 0.0001) increased defoliation risk due to Septoria leaf spot, caused by Septoria albopunctata. Defoliation occurred earlier for lower leaves than for upper leaves, but this effect was confounded in part with increased disease severity on lower leaves.


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