TY - JOUR
T1 - Aplicación de modelos estructurales marginales para estimar los efectos de la terapia antirretroviral en 5 cohortes de seroconvertores al virus de la inmunodeficiencia humana
AU - Pérez-Hoyos, Santiago
AU - Ferreros, Inmaculada
AU - Hernán, Miguel A.
AU - del Amo, Julia
AU - Hernández Aguado, Ildefonso
AU - Ferreros, Inmaculada
AU - Muga, Robert
AU - Sanvicens, Arantza
AU - Clotet, Bonaventura
AU - Tor, Jordi
AU - del Romero, Jorge
AU - Raposo, Paloma
AU - Rodríguez, Carmen
AU - García, Soledad
AU - Soriano, V. Vicente
AU - Hurtado, Isabel
AU - García de la Hera, Manoli
AU - Alastrúe, Ignacio
AU - Belda, Josefina
AU - Trullen, Joseph
AU - Fernández, Elisa
AU - Santos, Concha
AU - Tasa, Teresa
AU - García de Olalla, Patricia
AU - Caylà, Joan A.
AU - el Guerrero, Rafael
AU - Marco, Andrés
AU - Quintana, Manolo
AU - González, Cristina
AU - Ruisz, Isabel
AU - Perez, Rosario
AU - Castilla, Jesús
N1 - Funding Information:
Este trabajo ha sido financiado gracias a ayudas para la investigación de FIPSE (Fundación para la investigación y la prevención del sida en España) integrada por el Minis-terio de Sanidad, Abbott Laboratories, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme and Roche), (FIPSE 36349/02) y parcialmente al FIS (Fondo de Investigación Sanitaria) (FIS 02/0639) y a la ayuda de la Escuela Valenciana de Estudios para la Salud (EVES) 2005.
PY - 2007
Y1 - 2007
N2 - Objectives: Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence. Subjects and methods: We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment. Results: 917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68-1.49) using a Cox model without covariates and 0.90 (95% Cl, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% Cl, 0.49-1.12). Conclusions: The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.
AB - Objectives: Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence. Subjects and methods: We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment. Results: 917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68-1.49) using a Cox model without covariates and 0.90 (95% Cl, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% Cl, 0.49-1.12). Conclusions: The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.
KW - AIDS
KW - Marginal structural models
KW - Survival analysis
KW - Treatment efficacy
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UR - http://www.scopus.com/inward/citedby.url?scp=34047109685&partnerID=8YFLogxK
U2 - 10.1016/s0213-9111(07)71974-x
DO - 10.1016/s0213-9111(07)71974-x
M3 - Article
C2 - 17306191
AN - SCOPUS:34047109685
SN - 0213-9111
VL - 21
SP - 76
EP - 83
JO - Gaceta Sanitaria
JF - Gaceta Sanitaria
IS - 1
ER -