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Performance of methods to conduct mediation analysis with time-to-event outcomes |
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| Authors: | Lizbeth Burgos Ochoa Judith JM Rijnhart Brenda W Penninx Klaas J Wardenaar Jos WR Twisk Martijn W Heymans |
| Institution: | 1. Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands;2. Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands;3. Department of Psychiatry, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands;4. Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands |
| Abstract: | Previous studies have discouraged the use of the Cox proportional hazards (PH) model for traditional mediation analysis as it might provide biased results. Accelerated failure time (AFT) models have been proposed as an alternative for Cox PH models. In addition, the use of the potential outcomes framework has been proposed for mediation models with time-to-event outcomes. The aim of this paper is to investigate the performance of traditional mediation analysis and potential outcomes mediation analysis based on both the Cox PH and the AFT model. This is done by means of a Monte Carlo simulation study and the illustration of the methods using an empirical data set. Both the product-of-coefficients method of the traditional mediation analysis and the potential outcomes framework yield unbiased estimates with respect to their own underlying indirect effect value for simple mediation models with a time-to-event outcome and estimated based on Cox PH or AFT. |
| Keywords: | accelerated failure time causal inference Cox proportional hazards mediation analysis potential outcomes survival analysis time-to-event |