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Revista Colombiana de Estadística

Print version ISSN 0120-1751

Rev.Colomb.Estad. vol.45 no.1 Bogotá Jan./June 2022  Epub Jan 17, 2023

https://doi.org/10.15446/rce.v45n1.94553 

Artículos originales de investigación

Causal Mediation for Survival Data: A Unifying Approach via GLM

Mediación causal para datos de supervivencia: un enfoque unificador a través de GLM

MARCELO M. TADDEO1  a 

LEILA D. AMORIM1  b 

1 DEPARTMENTO DE ESTATÍSTICA, INSTITUTO DE MATEMÁTICA E ESTATÍSTICA, UNIVERSIDADE FEDERAL DA BAHIA, SALVADOR, BRAZIL


Abstract

Mediation analysis has been receiving much attention from the scientific community in the last years, mainly due to its ability to disentangle causal pathways from exposures to outcomes. Particularly, causal mediation analysis for time-to-event outcomes has been widely discussed using accelerated failures times, Cox and Aalen models, with continuous or binary mediator. We derive general expressions for the Natural Direct Effect and Natural Indirect Effect for the time-to-event outcome when the mediator is modeled using generalized linear models, which includes existing procedures as particular cases. We also define a responsiveness measure to assess the variations in continuous exposures in the presence of mediation. We consider a community-based prospective cohort study that investigates the mediation of hepatitis B in the relationship between hepatitis C and liver cancer. We fit different models as well as distinct distributions and link functions associated to the mediator. We also notice that estimation of NDE and NIE using different models leads to non-contradictory conclusions despite their effect scales. The survival models provide a compelling framework that is appropriate to answer many research questions involving causal mediation analysis. The extensions through GLMs for the mediator may encompass a broad field of medical research, allowing the often necessary control for confounding.

Key words: causal inference; generalized linear models; mediation; survival analysis

Resumen

El análisis de mediación ha recibido mucha atención en los últimos años, principalmente debido a su capacidad para desenredar las vías causales. Particularmente, mediación causal para el tiempo hasta el evento se ha discutido ampliamente utilizando tiempos de falla acelerados, modelos de Cox y Aalen, con mediador continuo o binario. Derivamos expresiones generales para el efecto directo natural y el efecto indirecto natural para el el tiempo hasta el evento cuando el mediador se modela utilizando modelos lineales generalizados, que incluyen procedimientos existentes como casos particulares. Definimos una medida para evaluar variaciones en exposiciones continuas en presencia de mediación. Consideramos un estudio de cohorte prospectivo que investiga la mediación de la hepatitis B en la relación entre la hepatitis C y el cáncer de hígado. Encajamos diferentes modelos, así como distintas distribuciones y funciones de enlace. Todos los enfoques dan como resultado evaluaciones consistentes de los effectos considerando sus correspondientes escalas. Los modelos de supervivencia proporcionan un marco convincente apropiado para responder a muchas preguntas de investigación que involucran mediación causal. Las extensiones a través de GLM para el mediador pueden abarcar un amplio campo de investigación médica, lo que permite el control necesario para los factores de confusión.

Palabras clave: análisis de supervivencia; inferencia causal; mediación; modelos lineales generalizados

Full text available only in PDF format

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Received: March 2021; Accepted: December 2021

aPh.D. E-mail: marcelo.magalhaes@ufba.br

bPh.D. E-mail: leiladen@ufba.br

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