Graduation Year

2016

Document Type

Thesis

Degree

M.S.P.H.

Degree Name

MS in Public Health (M.S.P.H.)

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Yougui Wu, Ph.D.

Committee Member

Yanzing Huang, Ph.D.

Committee Member

Amy Alman, Ph.D.

Keywords

Dementia, Hidden Markov model, misclassification

Abstract

Most of the chronic diseases have a well-known natural staging system through which the disease progression is interpreted. It is well established that the transition rates from one stage of disease to other stage can be modeled by multi state Markov models. But, it is also well known that the screening systems used to diagnose disease states may subject to error some times. In this study, a simulation study is conducted to illustrate the importance of addressing for misclassification in multi-state Markov models by evaluating and comparing the estimates for the disease progression Markov model with misclassification opposed to disease progression Markov model. Results of simulation study support that models not accounting for possible misclassification leads to bias. In order to illustrate method of accounting for misclassification is illustrated using dementia data which was staged as no cognitive impairment, mild cognitive impairment and dementia and diagnosis of dementia stage is prone to error sometimes. Subjects entered the study irrespective of their state of disease and were followed for one year and their disease state at follow up visit was recorded. This data is used to illustrate that application of multi state Markov model which is an example of Hidden Markov model in accounting for misclassification which is based on an assumption that the observed (misclassified) states conditionally depend on the underlying true disease states which follow the Markov process. The misclassification probabilities for all the allowed disease transitions were also estimated. The impact of misclassification on the effect of covariates is estimated by comparing the hazard ratios estimated by fitting data with progression multi state model and by fitting data with multi state model with misclassification which revealed that if misclassification has not been addressed the results are biased. Results suggest that the gene apoe ε4 is significantly associated with disease progression from mild cognitive impairment to dementia but, this effect was masked when general multi state Markov model was used. While there is no significant relation is found for other transitions.

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