Flexible modeling of the cumulative effects of time‐dependent exposures on the hazard

Statistics in Medicine - Tập 28 Số 27 - Trang 3437-3453 - 2009
Marie‐Pierre Sylvestre1, Michał Abrahamowicz1
1Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Que., Canada H3A 1A2.

Tóm tắt

AbstractMany epidemiological studies assess the effects of time‐dependent exposures, where both the exposure status and its intensity vary over time. One example that attracts public attention concerns pharmacoepidemiological studies of the adverse effects of medications. The analysis of such studies poses challenges for modeling the impact of complex time‐dependent drug exposure, especially given the uncertainty about the way effects cumulate over time and about the etiological relevance of doses taken in different time periods. We present a flexible method for modeling cumulative effects of time‐varying exposures, weighted by recency, represented by time‐dependent covariates in the Cox proportional hazards model. The function that assigns weights to doses taken in the past is estimated using cubic regression splines. We validated the method in simulations and applied it to re‐assess the association between exposure to a psychotropic drug and fall‐related injuries in the elderly. Copyright © 2009 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1038/sj.bjc.6690651

10.1002/(SICI)1097-0258(19970315)16:5<505::AID-SIM424>3.0.CO;2-Z

10.1111/j.0006-341X.2000.01105.x

10.1001/archinte.166.18.1961

10.1136/bmj.326.7383.255

Breslow NE, 1983, Multiplicative models and cohort analysis, Journal of the American Statistical Society, 78, 1, 10.1080/01621459.1983.10477915

10.1146/annurev.pu.09.050188.002315

10.1016/j.jclinepi.2005.01.021

Cox DR, 1972, Regression models and life tables (with Discussion), Journal of the Royal Statistical Society, Series B, 34, 187

10.1007/978-1-4612-6333-3

Abrahamowicz M, 1996, Time‐dependent hazard ratio: modeling and hypothesis testing with application in lupus nephritis, Journal of the Acoustical Society of America, 91, 1432

10.2307/2683222

10.1214/ss/1177013607

10.1214/ss/1177012761

10.2307/3315466

10.1214/aos/1176344136

10.1111/j.0006-341X.2000.00256.x

10.2307/2685338

LeebH PötscherBM. Can one estimate the unconditional distribution of post‐model‐selection estimators? MPRA Paper University Library of Munich Germany 2005. Available from:http://ideas.repec.org/p/pra/mprapa/72.html[20 March2008].

10.1080/03610910500415928

10.1080/01621459.1995.10476491

10.1007/978-1-4899-4541-9

10.1002/sim.1638

R Development Core Team, 2006, R: A Language and Environment for Statistical Computing

10.1111/j.1532-5415.2005.53108.x

10.1023/A:1020750810409

10.1002/sim.3092

Hastie TJ, 1990, Generalized Additive Models

Flurazepam, 2007, Compendium of Pharmaceuticals and Specialties

2000, WHO Collaborating Centre for Drug Statistics Methodology

10.1002/pds.908

10.1164/rccm.200210-1231OC

10.1093/aje/kwi307

10.7326/0003-4819-145-5-200609050-00009

10.1136/bmj.322.7288.704

10.1002/sim.2519

10.1080/01621459.1992.10476248

10.1002/sim.3400

Hastie T, 1993, Varying‐coefficient models, Journal of the Royal Statistical Society, Series B, 55, 757

10.1111/j.1541-0420.2005.030905.x

10.2307/2532940

10.1016/j.jclinepi.2004.10.012

10.1007/s10654-007-9106-5

10.1093/aje/kwg231

Berry G, 1979, Asbestosis: a study of dose–response relationships in an asbestos textile factory, British Journal of Industrial Medicine, 36, 98

Lundin FD, 1979, An Exposure–Time–Response Model for Lung Cancer Mortality in Uranium Miners Effects of Radiation Exposure, Age and Cigarette Smoking, 243