Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis

Béranger Lueza, Federico Rotolo, Julia Bonastre, Jean Pierre Pignon, Stefan Michiels

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    37 Citations (Scopus)

    Résumé

    Background: The difference in restricted mean survival time (rmstD t), the area between two survival curves up to time horizon t, 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 rmstD t from an IPD meta-analysis. Methods: We compared four methods: 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 t, 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 rmstD t, except with non-proportional hazards at t = 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 rmstD t. Overall, the Pooled Kaplan-Meier method with DerSimonian-Laird random effects formed the best compromise in terms of bias and variance. The rmstD (t = 10 years ) 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.

    langue originaleAnglais
    Numéro d'article37
    journalBMC Medical Research Methodology
    Volume16
    Numéro de publication1
    Les DOIs
    étatPublié - 29 mars 2016

    Contient cette citation