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Interval Estimation of the Absolute Risk of an Event with Competing Risks Using Proportional Regression of Cause-Specific Hazards

Received: 4 April 2022    Accepted: 19 April 2022    Published: 28 April 2022
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Abstract

It is often important to account for the effects of a competing risk when estimating the risk of a particular event of interest by estimating its absolute risk. Available methodology for interval estimation of the absolute risk using the proportional regression of cause-specific hazards (CSH) has been limited to situations with time-invariant covariates and a single random censoring mechanism, without accommodation of cohort sampling study designs. Here we derive asymptotic pointwise confidence intervals in closed form for the absolute risk of an event at a specified time (the value of the cumulative incidence function) in the presence of competing risks using proportional CSH regression, accommodating external time-dependent covariates, cohort sampling study designs and multiple censoring mechanisms. Different covariates may be used for the event of interest and the various competing risks. Consistent with the definition of absolute risk, the CSH method produces absolute risk estimates that are less than or approximately equal to corresponding “conditional” risk estimates that do not account for competing risks. An example shows that this property is not necessarily shared by methods based on subdistribution hazard regression. Simulation studies indicate that the CSH method confidence intervals computed on the log cumulative hazard or the risk scale have coverage probabilities that approximate the nominal level for small and moderate samples, provided that the number of events per covariate is at least 10 and, when using cohort sampling, the ratio of patients without events to patients with events is at least 2:1.

Published in American Journal of Applied Mathematics (Volume 10, Issue 2)
DOI 10.11648/j.ajam.20221002.15
Page(s) 59-85
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Absolute Risk, Cause-Specific Hazards, Cohort Sampling, Competing Risks, Cumulative Incidence Function, Interval Estimation, Time-Dependent Covariates

References
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[3] Gooley, T. A., Leisenring, W., Crowley, J., & Storer, B. E. (1999). Estimation of Failure Probabilities in the Presence of Competing Risks: New Representations of Old Estimators. Statistics in Medicine, 18, 695–706.
[4] Satagopan, J. M., Ben-Porat, L., Berwick, M., Robson, M., Kutler, D., & Auerbach, A. D. (2004). A Note on Competing Risks in Survival Data Analysis. British Journal of Cancer, 91, 1229–1235.
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[15] Bryant, J., & Dignam, J. (2004). Semiparametric Models for Cumulative Incidence Functions. Biometrics, 6, 182–190.
[16] Tsiatis, A. (1981) A Large Sample Study of Cox’s Regression Model. The Annals of Statistics 9, 93–108.
[17] Efron, B. (1977). The Efficiency of Cox’s Likelihood Function for Censored Data. Journal of the American Statistical Association, 72, 557–565.
[18] Byar, D. P., & Green, S. B. (1980). The Choice of Treatment for Cancer Patients Based on Covariate Information: Application to Prostate Cancer. Bulletin Cancer, Paris, 67, 477–488.
[19] Andrews, D. F., & Herzberg, A. M. (1985). Data: A Collection of Problems from Many Fields for the Student and Research Worker. Springer-Verlag, New York.
[20] Lin, D. Y., Wei, L. J., & Ying, Z. (1993). Checking the Cox Model with Cumulative Sums of Martingale-Based Residuals. Biometrika 80, 557–572.
[21] Geskus, R. B. (2011) Cause-Specific Cumulative Incidence Estimation and the Fine and Gray Model Under Both Left Truncation and Right Censoring. Biometrics, 67, 39–49.
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Cite This Article
  • APA Style

    Michael Richard Crager, Jerome Victor Braun. (2022). Interval Estimation of the Absolute Risk of an Event with Competing Risks Using Proportional Regression of Cause-Specific Hazards. American Journal of Applied Mathematics, 10(2), 59-85. https://doi.org/10.11648/j.ajam.20221002.15

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    ACS Style

    Michael Richard Crager; Jerome Victor Braun. Interval Estimation of the Absolute Risk of an Event with Competing Risks Using Proportional Regression of Cause-Specific Hazards. Am. J. Appl. Math. 2022, 10(2), 59-85. doi: 10.11648/j.ajam.20221002.15

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    AMA Style

    Michael Richard Crager, Jerome Victor Braun. Interval Estimation of the Absolute Risk of an Event with Competing Risks Using Proportional Regression of Cause-Specific Hazards. Am J Appl Math. 2022;10(2):59-85. doi: 10.11648/j.ajam.20221002.15

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  • @article{10.11648/j.ajam.20221002.15,
      author = {Michael Richard Crager and Jerome Victor Braun},
      title = {Interval Estimation of the Absolute Risk of an Event with Competing Risks Using Proportional Regression of Cause-Specific Hazards},
      journal = {American Journal of Applied Mathematics},
      volume = {10},
      number = {2},
      pages = {59-85},
      doi = {10.11648/j.ajam.20221002.15},
      url = {https://doi.org/10.11648/j.ajam.20221002.15},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajam.20221002.15},
      abstract = {It is often important to account for the effects of a competing risk when estimating the risk of a particular event of interest by estimating its absolute risk. Available methodology for interval estimation of the absolute risk using the proportional regression of cause-specific hazards (CSH) has been limited to situations with time-invariant covariates and a single random censoring mechanism, without accommodation of cohort sampling study designs. Here we derive asymptotic pointwise confidence intervals in closed form for the absolute risk of an event at a specified time (the value of the cumulative incidence function) in the presence of competing risks using proportional CSH regression, accommodating external time-dependent covariates, cohort sampling study designs and multiple censoring mechanisms. Different covariates may be used for the event of interest and the various competing risks. Consistent with the definition of absolute risk, the CSH method produces absolute risk estimates that are less than or approximately equal to corresponding “conditional” risk estimates that do not account for competing risks. An example shows that this property is not necessarily shared by methods based on subdistribution hazard regression. Simulation studies indicate that the CSH method confidence intervals computed on the log cumulative hazard or the risk scale have coverage probabilities that approximate the nominal level for small and moderate samples, provided that the number of events per covariate is at least 10 and, when using cohort sampling, the ratio of patients without events to patients with events is at least 2:1.},
     year = {2022}
    }
    

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    AU  - Michael Richard Crager
    AU  - Jerome Victor Braun
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    PY  - 2022
    N1  - https://doi.org/10.11648/j.ajam.20221002.15
    DO  - 10.11648/j.ajam.20221002.15
    T2  - American Journal of Applied Mathematics
    JF  - American Journal of Applied Mathematics
    JO  - American Journal of Applied Mathematics
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    UR  - https://doi.org/10.11648/j.ajam.20221002.15
    AB  - It is often important to account for the effects of a competing risk when estimating the risk of a particular event of interest by estimating its absolute risk. Available methodology for interval estimation of the absolute risk using the proportional regression of cause-specific hazards (CSH) has been limited to situations with time-invariant covariates and a single random censoring mechanism, without accommodation of cohort sampling study designs. Here we derive asymptotic pointwise confidence intervals in closed form for the absolute risk of an event at a specified time (the value of the cumulative incidence function) in the presence of competing risks using proportional CSH regression, accommodating external time-dependent covariates, cohort sampling study designs and multiple censoring mechanisms. Different covariates may be used for the event of interest and the various competing risks. Consistent with the definition of absolute risk, the CSH method produces absolute risk estimates that are less than or approximately equal to corresponding “conditional” risk estimates that do not account for competing risks. An example shows that this property is not necessarily shared by methods based on subdistribution hazard regression. Simulation studies indicate that the CSH method confidence intervals computed on the log cumulative hazard or the risk scale have coverage probabilities that approximate the nominal level for small and moderate samples, provided that the number of events per covariate is at least 10 and, when using cohort sampling, the ratio of patients without events to patients with events is at least 2:1.
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Author Information
  • Department of Biostatistics, Exact Sciences Corporation, Redwood City, USA

  • Department of Biostatistics, Exact Sciences Corporation, Redwood City, USA

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