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Discrimination and Calibration of Prognostic Survival Models

Clinicians employ prognostic survival models for diseases such as coronary heart disease and cancer to inform patients about risks, treatments, and clinical decisions (Altman and Royston 2000). These prognostic models are not useful unless they are valid in the population to which they are applied. There are no generally accepted algorithms for assessing the validity of an external survival model in a new population. Researchers often invoke measures of predictive accuracy, the degree to which predicted outcomes match observed outcomes (Justice et al. 1999). One component of predictive accuracy is discrimination, the ability of the model to correctly rank the individuals in the sample by risk. A common measure of discrimination for prognostic survival models is the concordance index, also called the c-statistic. We utilize the concordance index to determine the discrimination of Framingham-based Cox and Log-logistic models of coronary heart disease (CHD) death in cohorts from the Diverse Populations Collaboration, a collection of studies that encompasses many ethnic, geographic, and socioeconomic groups. Pencina and D'Agostino presented a confidence interval for the concordance index when assessing the discrimination of an external prognostic model. We perform simulations to determine the robustness of their confidence interval when measuring discrimination during internal validation. The Pencina and D'Agostino confidence interval is not valid in the internal validation setting because their assumption of mutually independent observations is violated. We compare the Pencina and D'Agostino confidence interval to a bootstrap confidence interval that we propose that is valid for the internal validation. We specifically discern the performance of the interval when the same sample is used to both fit and determine the validity of a prognostic model. The framework for our simulations is a Weibull proportional hazards model of CHD death fit to the Framingham exam 4 data. We then focus on the second component of accuracy, calibration, which measures the agreement between the observed and predicted event rates for groups of patients (Altman and Royston 2000). In 2000, van Houwelingen introduced a method called validation by calibration to allow a clinician to assess the validity of a well-accepted published survival model on his/her own patient population and adjust the published model to fit that population. Van Houwelingen embeds the published model into a new model with only 3 parameters which helps combat the overfitting that occurs when models with many covariates are fit on data sets with a small number of events. We explore validation by calibration as a tool to adjust models when an external model over- or underestimates risk. Van Houwelingen discusses the general method and then focusses on the proportional hazards model. There are situations where proportional hazards may not hold, thus we extend the methodology to the Log-logistic accelerated failure time model. We perform validation by calibration of Framingham-based Cox and Log-logistic models of CHD death to cohorts from the Diverse Populations Collaboration. Lastly, we conduct simulations that investigate the power of the global Wald validation by calibration test. We study its power to reject an invalid proportional hazards or Log-logistic accelerated failure time model under various scale and/or shape misspecifications. / A Dissertation submitted to the Department of Statistics in partial fulfillment of the requirements for the degree of
Doctor of Philosophy. / Spring Semester, 2009. / December 18, 2008. / Transportable, Generalizable, Validation, Framingham, Log-logistic, Reproducible / Includes bibliographical references. / Myles Hollander, Professor Co-Directing Thesis; Daniel McGee, Professor Co-Directing Thesis; Myra Hurt, Outside Committee Member; XuFeng Niu, Committee Member.
ContributorsSimino, Jeannette M. (authoraut), Hollander, Myles (professor co-directing thesis), McGee, Daniel (professor co-directing thesis), Hurt, Myra (outside committee member), Niu, XuFeng (committee member), Department of Statistics (degree granting department), Florida State University (degree granting institution)
PublisherFlorida State University, Florida State University
Source SetsFlorida State University
LanguageEnglish, English
Detected LanguageEnglish
TypeText, text
Format1 online resource, computer, application/pdf
RightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them.

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