scholarly journals Estimating restricted mean survival time and expected life-years lost in the presence of competing risks within flexible parametric survival models

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarwar I. Mozumder ◽  
Mark J. Rutherford ◽  
Paul C. Lambert

Abstract Background Royston-Parmar flexible parametric survival models (FPMs) can be fitted on either the cause-specific hazards or cumulative incidence scale in the presence of competing risks. An advantage of modelling within this framework for competing risks data is the ease at which alternative predictions to the (cause-specific or subdistribution) hazard ratio can be obtained. Restricted mean survival time (RMST), or restricted mean failure time (RMFT) on the mortality scale, is one such measure. This has an attractive interpretation, especially when the proportionality assumption is violated. Compared to similar measures, fewer assumptions are required and it does not require extrapolation. Furthermore, one can easily obtain the expected number of life-years lost, or gained, due to a particular cause of death, which is a further useful prognostic measure as introduced by Andersen. Methods In the presence of competing risks, prediction of RMFT and the expected life-years lost due to a cause of death are presented using Royston-Parmar FPMs. These can be predicted for a specific covariate pattern to facilitate interpretation in observational studies at the individual level, or at the population-level using standardisation to obtain marginal measures. Predictions are illustrated using English colorectal data and are obtained using the Stata post-estimation command, standsurv. Results Reporting such measures facilitate interpretation of a competing risks analysis, particularly when the proportional hazards assumption is not appropriate. Standardisation provides a useful way to obtain marginal estimates to make absolute comparisons between two covariate groups. Predictions can be made at various time-points and presented visually for each cause of death to better understand the overall impact of different covariate groups. Conclusions We describe estimation of RMFT, and expected life-years lost partitioned by each competing cause of death after fitting a single FPM on either the log-cumulative subdistribution, or cause-specific hazards scale. These can be used to facilitate interpretation of a competing risks analysis when the proportionality assumption is in doubt.

2021 ◽  
Author(s):  
Sarwar Islam Mozumder ◽  
Mark Rutherford ◽  
Paul Lambert

Abstract Background Royston-Parmar flexible parametric survival models (FPMs) can be fitted on either the cause-specific hazards or cumulative incidence scale in the presence of competing risks. An advantage of modelling within this framework for competing risks data is the ease at which alternative predictions to the (cause-specific or subdistribution) hazard ratio can be obtained. Restricted mean survival time (RMST) is one such measure. This has an attractive interpretation, especially when the proportionality assumption is violated. Compared to similar measures, fewer assumptions are required and it does not require extrapolation. Furthermore, one can easily obtain the expected number of life-years lost, or gained, due to a particular cause of death, which is a further useful prognostic measure as introduced by Andersen. Methods We present various measures, including the expected life-years lost due to a cause of death, which can be predicted for a specific covariate pattern to facilitate interpretation in observational studies. Summaries are also provided at the population-level using standardisation to obtain marginal measures. RMST is obtained in the presence of competing risks using Royston-Parmar FPMs. Predictions are illustrated using English colorectal data and are obtained using the Stata post-estimation command, standsurv. Results Reporting such measures facilitate interpretation of a competing risks analysis, particularly when the proportional hazards assumption is not appropriate. Standardisation provides a useful way to obtain marginal estimates to make absolute comparisons between two covariate groups. Predictions can be made at various time-points and presented visually for each cause of death to better understand the overall impact of different covariate groups. Conclusions We describe estimation of RMST and expected life-years lost, both partitioned by each competing cause of death after fitting a single FPM on either the log-cumulative subdistribution, or cause-specific hazards scale. These can be used to facilitate interpretation of a competing risks analysis when the proportionality assumption is in doubt.


2020 ◽  
Author(s):  
Sarwar Islam Mozumder ◽  
Paul Lambert ◽  
Mark Rutherford

Abstract We present various measures, specifically the expected life-years list due to a cause of death, that can be predicted for a specific covariate pattern. These can also be summarised at the population-level using standardisation to obtain marginal measures. The restricted mean survival time (RMST) measure can be obtained in the presence of competing risks using Royston-Parmar flexible parametric survival models (FPMs). Royston-Parmar FPMs can be fitted on either the cause-specific hazards or cumulative incidence scale in the presence of competing risks. An advantage of modelling within this framework for competing risks data is the ease at which other alternative predictions to the (cause-specific or subdistribution) hazard ratio can be obtained. The RMST estimate is one such measure. This has an attractive interpretation, especially when the proportionality assumption is violated. In addition to this, compared to similar measures, fewer assumptions are required and it does not require extrapolation. Furthermore, one can easily obtain the expected number of life-years lost, or gained, due to a particular cause of death, which is a further useful prognostic measure. We describe estimation of RMST after fitting a FPM on either the log-cumulative subdistribution, or cause-specific hazards scale. As an illustration of reporting such measures to facilitate interpretation of a competing risks analysis, models are fitted to English colorectal data.


2020 ◽  
Author(s):  
Sarwar Islam Mozumder ◽  
Mark Rutherford ◽  
Paul Lambert

Abstract We present various measures, specifically the expected life-years list due to a cause of death, that can be predicted for a specific covariate pattern to facilitate interpretation in observational studies. These can also be summarised at the population-level using standardisation to obtain marginal measures. The restricted mean survival time (RMST) measure can be obtained in the presence of competing risks using Royston-Parmar flexible parametric survival models (FPMs). Royston-Parmar FPMs can be fitted on either the cause-specific hazards or cumulative incidence scale in the presence of competing risks. An advantage of modelling within this framework for competing risks data is the ease at which other alternative predictions to the (cause-specific or subdistribution) hazard ratio can be obtained. The RMST estimate is one such measure. This has an attractive interpretation, especially when the proportionality assumption is violated. In addition to this, compared to similar measures, fewer assumptions are required and it does not require extrapolation. Furthermore, one can easily obtain the expected number of life-years lost, or gained, due to a particular cause of death, which is a further useful prognostic measure. We describe estimation of RMST after fitting a FPM on either the log-cumulative subdistribution, or cause-specific hazards scale. As an illustration of reporting such measures to facilitate interpretation of a competing risks analysis, models are fitted to English colorectal data.


Stats ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 107-119 ◽  
Author(s):  
Szilárd Nemes ◽  
Erik Bülow ◽  
Andreas Gustavsson

Restricted Mean Survival Time ( R M S T ) experiences a renaissance and is advocated as a model-free, easy to interpret alternative to proportional hazards regression and hazard rates with implication in causal inference. Estimation of R M S T and associated variance is mainly done by numerical integration of Kaplan–Meier curves. In this paper we briefly review the two main alternatives to the Kaplan–Meier method; analysis based on pseudo-observations, and the flexible parametric survival method. Using computer simulations, we assess the efficacy of the three methods compared to a fully parametric approach where the distribution of survival times is known. Thereafter, the three methods are directly compared without any distributional assumption for the survival data. Generally, flexible parametric survival methods outperform both competitors, however the differences are small.


Author(s):  
Junshan Qiu ◽  
Dali Zhou ◽  
H.M. Jim Hung ◽  
John Lawrence ◽  
Steven Bai

2019 ◽  
Vol 2 (1) ◽  
pp. 66-68 ◽  
Author(s):  
Andrea Messori ◽  
Vera Damuzzo ◽  
Laura Agnoletto ◽  
Luca Leonardi ◽  
Marco Chiumente ◽  
...  

2021 ◽  
Vol 41 (4) ◽  
pp. 476-484
Author(s):  
Daniel Gallacher ◽  
Peter Kimani ◽  
Nigel Stallard

Previous work examined the suitability of relying on routine methods of model selection when extrapolating survival data in a health technology appraisal setting. Here we explore solutions to improve reliability of restricted mean survival time (RMST) estimates from trial data by assessing model plausibility and implementing model averaging. We compare our previous methods of selecting a model for extrapolation using the Akaike information criterion (AIC) and Bayesian information criterion (BIC). Our methods of model averaging include using equal weighting across models falling within established threshold ranges for AIC and BIC and using BIC-based weighted averages. We apply our plausibility assessment and implement model averaging to the output of our previous simulations, where 10,000 runs of 12 trial-based scenarios were examined. We demonstrate that removing implausible models from consideration reduces the mean squared error associated with the restricted mean survival time (RMST) estimate from each selection method and increases the percentage of RMST estimates that were within 10% of the RMST from the parameters of the sampling distribution. The methods of averaging were superior to selecting a single optimal extrapolation, aside from some of the exponential scenarios where BIC already selected the exponential model. The averaging methods with wide criterion-based thresholds outperformed BIC-weighted averaging in the majority of scenarios. We conclude that model averaging approaches should feature more widely in the appraisal of health technologies where extrapolation is influential and considerable uncertainty is present. Where data demonstrate complicated underlying hazard rates, funders should account for the additional uncertainty associated with these extrapolations in their decision making. Extended follow-up from trials should be encouraged and used to review prices of therapies to ensure a fair price is paid.


2020 ◽  
Vol 19 (4) ◽  
pp. 436-453 ◽  
Author(s):  
Takahiro Hasegawa ◽  
Saori Misawa ◽  
Shintaro Nakagawa ◽  
Shinichi Tanaka ◽  
Takanori Tanase ◽  
...  

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