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Incorporating sampling weights into robust estimation of Cox proportional hazards regression model, with illustration in the Multi-Ethnic Study of Atherosclerosis.

TitleIncorporating sampling weights into robust estimation of Cox proportional hazards regression model, with illustration in the Multi-Ethnic Study of Atherosclerosis.
Publication TypeJournal Article
Year of Publication2020
AuthorsSitlani, CM, Lumley, T, McKnight, B, Rice, KM, Olson, NC, Doyle, MF, Huber, SA, Tracy, RP, Psaty, BM, Delaney, JAC
JournalBMC Med Res Methodol
Volume20
Issue1
Pagination62
Date Published2020 03 14
ISSN1471-2288
Abstract<p><b>BACKGROUND: </b>Cox proportional hazards regression models are used to evaluate associations between exposures of interest and time-to-event outcomes in observational data. When exposures are measured on only a sample of participants, as they are in a case-cohort design, the sampling weights must be incorporated into the regression model to obtain unbiased estimating equations.</p><p><b>METHODS: </b>Robust Cox methods have been developed to better estimate associations when there are influential outliers in the exposure of interest, but these robust methods do not incorporate sampling weights. In this paper, we extend these robust methods, which already incorporate influence weights, so that they also accommodate sampling weights.</p><p><b>RESULTS: </b>Simulations illustrate that in the presence of influential outliers, the association estimate from the weighted robust method is closer to the true value than the estimate from traditional weighted Cox regression. As expected, in the absence of outliers, the use of robust methods yields a small loss of efficiency. Using data from a case-cohort study that is nested within the Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study, we illustrate differences between traditional and robust weighted Cox association estimates for the relationships between immune cell traits and risk of stroke.</p><p><b>CONCLUSIONS: </b>Robust weighted Cox regression methods are a new tool to analyze time-to-event data with sampling, e.g. case-cohort data, when exposures of interest contain outliers.</p>
DOI10.1186/s12874-020-00945-9
Alternate JournalBMC Med Res Methodol
PubMed ID32169052
PubMed Central IDPMC7071747
Grant ListR01 HL120854 / HL / NHLBI NIH HHS / United States
R01 HL103405 / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
R00 HL129045 / HL / NHLBI NIH HHS / United States
ePub date: 
20/03