Graduation Year

2013

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Public Health

Major Professor

Fred W. Huffer

Co-Major Professor

James Mortimer

Keywords

accelerated failure time, AIC, distance effect, survival analysis

Abstract

Patient survival post liver transplant (LT) is important to both the patient and the center's accreditation, but over the years physicians have noticed that distant patients struggle with post LT care. I hypothesized that patient's distance from the transplant center had a detrimental effect on post LT survival. I suspected Hepatitis C (HCV) and Hepatocellular Carcinoma (HCC) patients would deteriorate due to their recurrent disease and there is a need for close monitoring post LT. From the current literature it was not clear if patients' distance from a transplant center affects outcomes post LT. Firozvi et al. (Firozvi AA, 2008) reported no difference in outcomes of LT recipients living 3 hours away or less. This study aimed to examine outcomes of LT recipients based on distance from a transplant center. I hypothesized that the effect of distance from a LT center was detrimental after adjusting for HCV and HCC status.

Methods:

This was a retrospective single center study of LT recipients transplanted between 1996 and 2012. 821 LT recipients were identified who qualified for inclusion in the study. Survival analysis was performed using standard methods as well as a newly developed Monte Carlo (MC) approach for change point detection. My new methodology, allowed for detection of both a change point in distance and a time by maximizing the two parameter score function (M2p) over a two dimensional grid of distance and time values. Extensive simulations using both standard distributions and data resembling the LT data structure were used to prove the functionality of the model.

Results:

Five year survival was 0.736 with a standard error of 0.018. Using Cox PH it was demonstrated that patients living beyond 180 miles had a hazard ratio (HR) of 2.68 (p-value<0.004) compared to those within 180 miles from the transplant center. I was able to confirm these results using KM and HCV/HCC adjusted AFT, while HCV and HCC adjusted LR confirmed the distance effect at 180 miles (p=0.0246), one year post LT. The new statistic that has been labeled M2p allows for simultaneous dichotomization of distance in conjunction with the identification of a change point in the hazard function. It performed much better than the previously available statistics in the standard simulations. The best model for the data was found to be extension 3 which dichotomizes the distance Z, replacing it by I(Z>c), and then estimates the change point c and tau.

Conclusions:

Distance had a detrimental effect and this effect was observed at 180 miles from the transplant center. Patients living beyond 180 miles from the transplant center had 2.68 times the death rate compared to those living within the 180 mile radius. Recipients with HCV fared the worst with the distance effect being more pronounced (HR of 3.72 vs. 2.68). Extensive simulations using different parameter values in both standard simulations and simulations resembling LT data, proved that these new approaches work for dichotomizing a continuous variable and finding a point beyond which there is an incremental effect from this variable. The recovered values were very close to the true values and p-values were small.

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