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Lifetime Data Analysis

, Volume 24, Issue 3, pp 425–442 | Cite as

The competing risks Cox model with auxiliary case covariates under weaker missing-at-random cause of failure

  • Daniel Nevo
  • Reiko Nishihara
  • Shuji Ogino
  • Molin Wang
Article

Abstract

In the analysis of time-to-event data with multiple causes using a competing risks Cox model, often the cause of failure is unknown for some of the cases. The probability of a missing cause is typically assumed to be independent of the cause given the time of the event and covariates measured before the event occurred. In practice, however, the underlying missing-at-random assumption does not necessarily hold. Motivated by colorectal cancer molecular pathological epidemiology analysis, we develop a method to conduct valid analysis when additional auxiliary variables are available for cases only. We consider a weaker missing-at-random assumption, with missing pattern depending on the observed quantities, which include the auxiliary covariates. We use an informative likelihood approach that will yield consistent estimates even when the underlying model for missing cause of failure is misspecified. The superiority of our method over naive methods in finite samples is demonstrated by simulation study results. We illustrate the use of our method in an analysis of colorectal cancer data from the Nurses’ Health Study cohort, where, apparently, the traditional missing-at-random assumption fails to hold.

Keywords

Competing risks Masked cause of failure Missing-at-random Subtype analysis 

Notes

Acknowledgements

We thank two anonymous reviewers and the associate editor for insightful comments and suggestions that improved the paper.

Supplementary material

10985_2017_9401_MOESM1_ESM.pdf (317 kb)
Supplementary material 1 (pdf 317 KB)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Daniel Nevo
    • 1
  • Reiko Nishihara
    • 2
  • Shuji Ogino
    • 3
    • 4
    • 5
  • Molin Wang
    • 1
  1. 1.Departments of Biostatistics and EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  2. 2.Departments of Epidemiology and NutritionHarvard T.H. Chan School of Public HealthBostonUSA
  3. 3.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  4. 4.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  5. 5.Division of MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Womens Hospital and Harvard Medical SchoolBostonUSA

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