Evaluation of Multiple Detection Modalities for Nasopharyngeal Carcinoma

• Main Authors: Chih-Chieh Tseng, 曾智傑
• Other Authors: 陳秀熙
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/19804621219460424323

碩士 === 國立臺灣大學 === 預防醫學研究所 === 95 === Disease screening with single detection modality is convenient and cheap, but it may be less effectiveness in terms of sensitivity and specificity. In order to solve this problem, multiple detection modalities may be needed. However, the methodology of combining multiple detection modalities is difficult, such as the combined sensitivity and specificity, detection ability, and cost-effectiveness analysis. Take screening of nasopharyngeal carcinoma (NPC) with EBV VCA IgA for example. The specificity of EBV VCA IgA is not good enough that the false positive rate is too high. Although multiple detection modalities can raise sensitivity and specificity at the same time, it will also increase the cost of screening. Therefore, the cost-effectiveness analysis of multiple detection modalities ensures. The purpose of this study is to complete (1) the meta-analysis of sensitivity and specificity of each detection modality using Bayesian fixed-effect and random-effect model, (2) conditional dependency model of multiple detection modalities, (3) the relation between sensitivity and sojourn time using multi-state model, (4) the cost-effectiveness of multiple detection modalities for NPC. The methodology part of multiple detection modalities is described as following: (1) We systemically searched Medline and PubMed with the key words of screening, Ebstein-barr virus(EBV) and nasopharyngeal carcinoma. The meta-analysis of the included 36 literature was performed with Bayesian fixed-effect and random-effect model to deal with the heterogeneity between each study. The results of sensitivity and specificity of each detection modality were obtained. (2) We used Bayesian conditional dependency model to estimate the combined sensitivity and specificity of detection modalities. This model adjusted with the biological correlation between combined detection modalities. (3)With the relation of sensitivity and pre-clinical detectable phase (PCPD, sojourn time), we estimated the earliness of detectable phase of each modalities. (4)We proposed a multi-state model for a mixture type of tumor progression. We also simulated the parameters for the mixture type model with the method of Monte Carlo simulation. Validation of the parameters was also performed. (5) We completed the cost-effectiveness analysis of NPC screening with different screening strategies using the parameters we generated in (4). The results of meta-analysis of the sensitivity for different detection modalities for nasopharyngeal carcinoma with Bayesian random-effect model are described as following. Serology of EBV BamHI-W region gene is the most sensitive detection modality (median value of 91%), followed by nasopharyngeal swab , EBV VCA IgA , EBV EA IgA , EBV EBNA, and nasopharyngoscope. In the same way, the most specific detection modality is nasopharyngoscope (median value of 98%), followed by EBV EA IgA, nasopharyngeal swab, EBV BamHI-W, EBV VCA IgA and EBV EBNA. The results of Bayesian fixed-effect model were similar to that of random-effect model. Using DIC (Deviation information criteria) to compare the two models, we found the random-effect model is better than fixed-effect model. The results of PCDP of each detection modalities were obtained with the relation between sensitivities, transitional rates, and PCDP. The PCDP of EBV BamHI-W is 2.79 year, nasopharyngeal swab is 2.77 year, EBV VCA IgA is 2.68 year, EBV EA IgA, EBV EBNA and nasopharyngoscope are 2.34 year, and nasopharyngeal cytology is 2.22 year. The PCDP of combining nasopharyngoscope and EBV VCA IgA, EBV EA IgA and EBV VCA IgA, and EBV EBNA and EBV VCA IgA is the same, 2.97 year. The PCDP of combining EBV BamHI-W and EBV VCA IgA is longest, 3.01 year. The estimated value is close to the true value in the model of mixture type tumor by simulation method. The sensitivity of simulation model is also close to that of meta-analysis. In cost-effectiveness analysis, the ICER (incremental cost-effectiveness ratio) is 365,095 when the strategy of no screening and 2-year screening with EBV VCA IgA is compared. The ICER is 442,145 with no screening and annually screening with EBV VCA IgA. The ICER is 1,091,533 with no screening and annually screening with combining EBV VCA IgA and nasopharyngoscope. Compared with no screening, 2-year screening with EBV VCA IgA can reduce one NPC death per 17,857 screening, annual screening with EBV VCA IgA can reduce one NPC death per 23,622 screening, and annual screening with combining EBV VCA IgA and nasopharyngoscope can reduce one NPC death per 21,739. The novelty of this study is combining the idea of sensitivity and multi-state model. In this way, the sensitivity of detection modalities has taken the influence of time progression into account. This method can be applied in disease screening in terms of screening interval determination and cost-effectiveness analysis.