TY - JOUR

T1 - Analyzing differences between restricted mean survival time curves using pseudo-values

AU - Ambrogi, Federico

AU - Iacobelli, Simona

AU - Andersen, Per Kragh

PY - 2022

Y1 - 2022

N2 - Hazard ratios are ubiquitously used in time to event analysis to quantify treatment effects. Although hazard ratios are invaluable for hypothesis testing, other measures of association, both relative and absolute, may be used to fully elucidate study results. Restricted mean survival time (RMST) differences between groups have been advocated as useful measures of association. Recent work focused on model-free estimates of the difference in restricted mean survival through follow-up times, instead of focusing on a single time horizon. The resulting curve can be used to quantify the association in time units with a simultaneous confidence band. In this work a model-based estimate of the curve is proposed using pseudo-values allowing for possible covariate adjustment. The method is easily implementable with available software and makes possible to compute a simultaneous confidence region for the curve. The pseudo-values regression using multiple restriction times is in good agreement with the estimates obtained by standard direct regression models fixing a single restriction time. Moreover, the proposed method is flexible enough to reproduce the results of the non-parametric approach when no covariates are considered. Examples where it is important to adjust for baseline covariates will be used to illustrate the different methods together with some simulations.

AB - Hazard ratios are ubiquitously used in time to event analysis to quantify treatment effects. Although hazard ratios are invaluable for hypothesis testing, other measures of association, both relative and absolute, may be used to fully elucidate study results. Restricted mean survival time (RMST) differences between groups have been advocated as useful measures of association. Recent work focused on model-free estimates of the difference in restricted mean survival through follow-up times, instead of focusing on a single time horizon. The resulting curve can be used to quantify the association in time units with a simultaneous confidence band. In this work a model-based estimate of the curve is proposed using pseudo-values allowing for possible covariate adjustment. The method is easily implementable with available software and makes possible to compute a simultaneous confidence region for the curve. The pseudo-values regression using multiple restriction times is in good agreement with the estimates obtained by standard direct regression models fixing a single restriction time. Moreover, the proposed method is flexible enough to reproduce the results of the non-parametric approach when no covariates are considered. Examples where it is important to adjust for baseline covariates will be used to illustrate the different methods together with some simulations.

KW - RMST curve difference

KW - Pseudo-values

KW - Crossing survival curves

KW - ADJUVANT THERAPY

KW - HAZARD RATIO

KW - LIFE

KW - FLUOROURACIL

KW - LEVAMISOLE

KW - MODELS

U2 - 10.1186/s12874-022-01559-z

DO - 10.1186/s12874-022-01559-z

M3 - Journal article

C2 - 35300614

VL - 22

JO - B M C Medical Research Methodology

JF - B M C Medical Research Methodology

SN - 1471-2288

IS - 1

M1 - 71

ER -