Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis.
BMC Med Res Methodol
; 16: 37, 2016 Mar 29.
Article
em En
| MEDLINE
| ID: mdl-27025706
ABSTRACT
BACKGROUND:
The difference in restricted mean survival time ([Formula see text]), the area between two survival curves up to time horizon [Formula see text], is often used in cost-effectiveness analyses to estimate the treatment effect in randomized controlled trials. A challenge in individual patient data (IPD) meta-analyses is to account for the trial effect. We aimed at comparing different methods to estimate the [Formula see text] from an IPD meta-analysis.METHODS:
We compared fourmethods:
the area between Kaplan-Meier curves (experimental vs. control arm) ignoring the trial effect (Naïve Kaplan-Meier); the area between Peto curves computed at quintiles of event times (Peto-quintile); the weighted average of the areas between either trial-specific Kaplan-Meier curves (Pooled Kaplan-Meier) or trial-specific exponential curves (Pooled Exponential). In a simulation study, we varied the between-trial heterogeneity for the baseline hazard and for the treatment effect (possibly correlated), the overall treatment effect, the time horizon [Formula see text], the number of trials and of patients, the use of fixed or DerSimonian-Laird random effects model, and the proportionality of hazards. We compared the methods in terms of bias, empirical and average standard errors. We used IPD from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) and its updated version MAC-NPC2 for illustration that included respectively 1,975 and 5,028 patients in 11 and 23 comparisons.RESULTS:
The Naïve Kaplan-Meier method was unbiased, whereas the Pooled Exponential and, to a much lesser extent, the Pooled Kaplan-Meier methods showed a bias with non-proportional hazards. The Peto-quintile method underestimated the [Formula see text], except with non-proportional hazards at [Formula see text]= 5 years. In the presence of treatment effect heterogeneity, all methods except the Pooled Kaplan-Meier and the Pooled Exponential with DerSimonian-Laird random effects underestimated the standard error of the [Formula see text]. Overall, the Pooled Kaplan-Meier method with DerSimonian-Laird random effects formed the best compromise in terms of bias and variance. The [Formula see text] estimated with the Pooled Kaplan-Meier method was 0.49 years (95% CI [-0.06;1.03], p = 0.08) when comparing radiotherapy plus chemotherapy vs. radiotherapy alone in the MAC-NPC and 0.59 years (95% CI [0.34;0.84], p < 0.0001) in the MAC-NPC2.CONCLUSIONS:
We recommend the Pooled Kaplan-Meier method with DerSimonian-Laird random effects to estimate the difference in restricted mean survival time from an individual-patient data meta-analysis.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Análise de Sobrevida
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Neoplasias Nasofaríngeas
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Modelos Estatísticos
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article