TY - JOUR
T1 - Nonparametric assessment of differences between competing risk hazard ratios
T2 - Application to racial differences in pediatric chronic kidney disease progression
AU - Ng, Derek K.
AU - Antiporta, Daniel A.
AU - Matheson, Matthew B.
AU - Muñoz, Alvaro
N1 - Funding Information:
Data in this manuscript were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri–Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, PhD and Derek K. Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, U24-DK-66116). The CKiD website is located at http://statepi.jhsph.edu/ckid.
Funding Information:
Data in this manuscript were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children?s Mercy Hospital and the University of Missouri?Kansas City (Bradley Warady, MD) and Children?s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Mu?oz, PhD and Derek K. Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, U24-DK-66116). The CKiD website is located at http://statepi.jhsph.edu/ckid.
Publisher Copyright:
© 2020 Ng et al.
PY - 2020
Y1 - 2020
N2 - Associations between an exposure and multiple competing events are typically described by cause-specific hazard ratios (csHR) or subdistribution hazard ratios (sHR). However, diagnostic tools to assess differences between them have not been described. Under the proportionality assumption for both, it can be shown mathematically that the sHR and csHR must be equal, so reporting different time-constant sHR and csHR implies non-proportionality for at least one. We propose a simple, intuitive approach using the ratio of sHR/csHR to nonparametrically compare these metrics. In general, for the non-null case, there must be at least one event type for which the sHR and csHR differ, and the proposed diagnostic will be useful to identify these cases. Furthermore, once standard methods are used to estimate the csHR, multiplying it with our nonparametric estimate for the sHR/csHR ratio will yield estimates of sHR which fulfill intrinsic linkages of the subhazards that separate analysis may violate. In addition, for non-null cases, at least one must be time dependent (i.e., non-proportional), and thus our tool serves as an indirect test of the proportionality assumption. We applied this proposed diagnostic tool to data from a cohort of children with congenital kidney disease to describe racial differences in the time to first dialysis or first transplant and extend methods to include adjustment for socioeconomic factors.
AB - Associations between an exposure and multiple competing events are typically described by cause-specific hazard ratios (csHR) or subdistribution hazard ratios (sHR). However, diagnostic tools to assess differences between them have not been described. Under the proportionality assumption for both, it can be shown mathematically that the sHR and csHR must be equal, so reporting different time-constant sHR and csHR implies non-proportionality for at least one. We propose a simple, intuitive approach using the ratio of sHR/csHR to nonparametrically compare these metrics. In general, for the non-null case, there must be at least one event type for which the sHR and csHR differ, and the proposed diagnostic will be useful to identify these cases. Furthermore, once standard methods are used to estimate the csHR, multiplying it with our nonparametric estimate for the sHR/csHR ratio will yield estimates of sHR which fulfill intrinsic linkages of the subhazards that separate analysis may violate. In addition, for non-null cases, at least one must be time dependent (i.e., non-proportional), and thus our tool serves as an indirect test of the proportionality assumption. We applied this proposed diagnostic tool to data from a cohort of children with congenital kidney disease to describe racial differences in the time to first dialysis or first transplant and extend methods to include adjustment for socioeconomic factors.
KW - Cause-specific hazard ratios
KW - Chronic kidney disease
KW - Competing risk analysis
KW - Nonparametric methods
KW - Sub-distribution hazard ratios
KW - Survival analysis
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U2 - 10.2147/CLEP.S225763
DO - 10.2147/CLEP.S225763
M3 - Article
C2 - 32021474
AN - SCOPUS:85078673794
SN - 1179-1349
VL - 12
SP - 83
EP - 93
JO - Clinical Epidemiology
JF - Clinical Epidemiology
ER -