scholarly journals Generating survival times to simulate Cox proportional hazards models with time‐varying covariates

2012 ◽  
Vol 31 (29) ◽  
pp. 3946-3958 ◽  
Author(s):  
Peter C. Austin
2020 ◽  
Vol 12 (3) ◽  
pp. 324-339 ◽  
Author(s):  
Yunda Huang ◽  
Yuanyuan Zhang ◽  
Zong Zhang ◽  
Peter B. Gilbert

Abstract Time-to-event outcomes with cyclic time-varying covariates are frequently encountered in biomedical studies that involve multiple or repeated administrations of an intervention. In this paper, we propose approaches to generating event times for Cox proportional hazards models with both time-invariant covariates and a continuous cyclic and piecewise time-varying covariate. Values of the latter covariate change over time through cycles of interventions and its relationship with hazard differs before and after a threshold within each cycle. The simulations of data are based on inverting the cumulative hazard function and a log link function for relating the hazard function to the covariates. We consider closed-form derivations with the baseline hazard following the exponential, Weibull, or Gompertz distribution. We propose two simulation approaches: one based on simulating survival data under a single-dose regimen first before data are aggregated over multiple-dosing cycles and another based on simulating survival data directly under a multiple-dose regimen. We consider both fixed intervals and varying intervals of the drug administration schedule. The method’s validity is assessed in simulation experiments. The results indicate that the proposed procedures perform well in generating data that conform to their cyclic nature and assumptions of the Cox proportional hazards model.


2021 ◽  
Author(s):  
Douglas Barthold ◽  
Elizabeth Brouwer ◽  
Lee J. Barton ◽  
David E. Arterburn ◽  
Anirban Basu ◽  
...  

<b>Objective:</b> There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes (T2DM) following bariatric surgery and no published studies using weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. <p><b>Research Design and Methods:</b> Cox proportional hazards models examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. </p> <p><b>Results:</b> Patients (N=5,928) were 73% female, 49.8<u>+</u>10.3 years old, had BMI of 43.8<u>+</u>6.92 kg/m<sup>2</sup>, and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of their T2DM (mean time to remission 1.0 year). Using 0-5% TWL as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (range from HR=1.97 to 2.92). When categories above >25% TWL were examined, all had a likelihood of initial remission similar to 20-25% TWL. Patients who achieved >20% TWL were more likely to achieve initial T2DM remission than patients with 0-5% TWL, even if they were using insulin at the time of surgery.</p> <p><b>Conclusions: </b>Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.</p>


2019 ◽  
Vol 189 (3) ◽  
pp. 224-234
Author(s):  
Jamie M Madden ◽  
Finbarr P Leacy ◽  
Lina Zgaga ◽  
Kathleen Bennett

Abstract Studies have shown that accounting for time-varying confounding through time-dependent Cox proportional hazards models may provide biased estimates of the causal effect of treatment when the confounder is also a mediator. We explore 2 alternative approaches to addressing this problem while examining the association between vitamin D supplementation initiated after breast cancer diagnosis and all-cause mortality. Women aged 50–80 years were identified in the National Cancer Registry Ireland (n = 5,417) between 2001 and 2011. Vitamin D use was identified from linked prescription data (n = 2,570). We sought to account for the time-varying nature of vitamin D use and time-varying confounding by bisphosphonate use using 1) marginal structural models (MSMs) and 2) G-estimation of structural nested accelerated failure-time models (SNAFTMs). Using standard adjusted Cox proportional hazards models, we found a reduction in all-cause mortality in de novo vitamin D users compared with nonusers (hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.73, 0.99). Additional adjustment for vitamin D and bisphosphonate use in the previous month reduced the hazard ratio (HR = 0.45, 95% CI: 0.33, 0.63). Results derived from MSMs (HR = 0.44, 95% CI: 0.32, 0.61) and SNAFTMs (HR = 0.45, 95% CI: 0.34, 0.52) were similar. Utilizing MSMs and SNAFTMs to account for time-varying bisphosphonate use did not alter conclusions in this example.


2005 ◽  
Vol 24 (11) ◽  
pp. 1713-1723 ◽  
Author(s):  
Ralf Bender ◽  
Thomas Augustin ◽  
Maria Blettner

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