( 您好!臺灣時間:2021/03/05 00:21
字體大小: 字級放大   字級縮小   預設字形  


研究生(外文):Hendry Lukito
論文名稱:癌症轉移風險與經濟性評估: 半馬可夫鏈分析
論文名稱(外文):Risk and Economic Evaluation Associated to Cancer Metastasis: A Semi-Markov Analysis
指導教授(外文):Kung-Jeng Wang
口試委員(外文):Kung-Jeng Wang
外文關鍵詞:Monte Carlo simulationsemi-Markov processrisk and economic evaluationCancer metastasis
  • 被引用被引用:0
  • 點閱點閱:190
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:29
  • 收藏至我的研究室書目清單書目收藏:0
Cancer has become one of the leading causes of death. One major cause of its high mortality is attributed to the metastasized cancer. Analogously, the medical expenses for the cancer treatment have generated a socioeconomic burden. In this study, a semi-Markov model was developed to perform risk and economic evaluation associated to several types of cancer metastasis for lung, brain, liver and lymphoma cancer. A nationwide medical database in Taiwan was used to derive baseline study population and costs data. Covariates analysis investigated the influence of gender, age and medical expenses generated to the transition risk among states. Then, the aggregate time until development of metastasis, survivability from metastasis condition and lifetime medical costs were estimated through Monte Carlo simulation. From covariates analysis, we found that the risks of metastatic cancer occurrence is significantly reduced by high medical expenses spent to treat the disease. The 20 years median lifetime cost ranged from 399,397 NTD for lung cancer-brain metastasis case to 2,145,650 NTD for brain cancer-liver metastasis case. Simulation results also revealed a positive correlation between the expensed cost and patient’s lifetime. Breaking down the cost into its components, it is revealed that drugs made up the largest portion of all expenses, accounting for 35% in average. Moreover, it was also observable that most expenses decreased gradually after diagnosis. Moreover, sensitivity analysis provides a mechanism for policy makers to review or predict the impact of several change in current condition. In conclusion, this model provides a healthcare policy decision-making mechanism to understand the disease burden of cancer metastasis cases.
Abstract i
摘要 ii
Acknowledgement iii
Table of Contents iv
List of Tables vi
List of Figures vii
1.1. Research Background 1
1.2. Research Objective 4
1.3. Research Approach 4
1.4. Research Limitation 5
1.5. Research Outline 5
2.1. Cancer Basics 7
2.2. Taiwan’s NHIRD and Its Studies 9
2.3. Semi-Markov Model 12
2.4. Monte Carlo Simulation 16
3.1. Data Description 19
3.1.1. Data Source 19
3.1.2. Data Definition and Criterion 20
3.2. Data Processing Procedure 23
3.2.1. Study Population 23
3.2.2. Costing Methods 24
3.3. Multi-State Semi-Markov Modeling 26
3.3.1. Model Structure 26
3.3.2. Identification of Transition Probabilities and Covariates Analysis 28
3.4. Simulation Model Structure 32
4.1. Experiment Scenarios 35
4.1.1. Semi-Markov Modelling 35
4.1.2. Monte Carlo Simulation 36
4.1.3. Sensitivity Analysis 38
4.2. Results 38
4.2.1. Baseline data 38
4.2.2. Results from Semi-Markov Modelling 41
4.2.3. Semi-Markov Simulation 47
4.2.4. Sensitivity Analysis 57
4.2.5. Comparison to naive statistics 58
5.1. Discussion and Conclusion 60
5.2. Future Research 65
A. Distribution Functions of Medical Cost Components 72
B. Cost Components Proportion (Percentage) 75
C. Cost Components Plots Over Time 76
American Cancer Society. (2014). Cancer Facts & Figures 2014. Atlanta: American Cancer Society.
Austin, P. C., Ghali, W. A., & Tu, J. V. (2003). A Comparison of Several Regression Models for Analysing Cost of CABG Surgery. Statistics in Medicine, 2: 2799-2815.
Barbu, V. S., & Limnios, N. (2008). Semi-Markov Chains and Hidden Semi-Markov Models towards Application. New York: Springer Science+Business Media LLC.
Bonate, P. L. (2001). A Brief Introduction to Monte Carlo Simulation. Clinical Pharmacokinetics, 40(1): 15-22.
Brown, M. L., Riley, G. F., Schussler, N., & Etzioni, R. (2002). Estimating Health Care Costs Related to Cancer Treatment from SEER-Medicare Data. Medical Care, 40(8): 104-117.
Castelli, C., Combescure, C., Foucher, Y., & Daures, J.-P. (2007). Cost-Effectiveness Analysis in Colorectal Cancer Using a Semi-Markov Model. Statistics in Medicine, 26: 5557-5571.
Chang, H.-Y. (2009). Evaluation of Alternative Diagnosis-based Risk Adjustment Models and Morbidity Trajectories for Application in Taiwan. Baltimore: The Johns Hopkins University.
Chen, Y.-C., Yeh, H.-Y., Wu, J.-C., Haschler, I., Chen, T.-J., & Wetter, T. (2011). Taiwan's National Health Insurance Research Database Administrative Health Care Database as Study Object in Bibliometrics. Scientometrics, 86: 365-380.
Cheng, T.-M. (2003). Taiwan's new National Health Insurance Program: Genesis and Experience So Far. Health Affairs, 22(3): 61-76.
Chiang, C.-J., Chen, Y.-C., Chen, C.-J., You, S.-L., Lai, M.-S., & Force, T. C. (2010). Cancer Trends in Taiwan. Japanese Journal of Clinical Oncology, 40(10): 897–904.
Chiang, C.-W., Chiu, H.-F., Chen, C.-Y., Wu, H.-L., & Yang, C.-Y. (2006). Trends in The Use of Oral Antidiabetic Drugs by Outpatients in Taiwan: 1997-2003. Journal of Clinical Pharmacology and Therapeutics, 31: 73-82.
Chiang, T.-L. (1997). Taiwan's 1995 Health Care Reform. Health Policy, 39: 225-239.
Chien, C.-R., & Shih, Y.-C. (2012). Reconciling Cancer Care Costs Reported by Different Government Agencies in Taiwan: Why Costing Approach Matters? Value in Health Regional, 1: 111-117.
Chouaid, C., Molinier, L., Combescure, C., Daures, J. P., Housset, B., & Vergnenegre, A. (2004). Economics of the Clinical Management of Lung Cancer in France: an Analysis Using a Markov Model. British Journal of Cancer, 90: 397-402.
Chu, P.-C., Hwang, J.-S., Wang, J.-D., & Chang, Y.-Y. (2008). Estimation of the Financial Burden to the National Health Insurance for Patients with Major Cancers in Taiwan. Journal of Formosan Medical Association, 107(1): 54-63.
Cohen, B. L. (1990). Understanding Risk. In The Nuclear Energy Option. New York: Plenum Press.
Cox, D. R. (1972). Regression Models and Life-Tables. Journal of the Royal Statistical Society. Series B (Methodological), 34(2): 187-220.
David, M. C., Bensink, M., Higashi, H., Donald, M., Alati, R., & Ware, R. (2012). Monte Carlo Simulation of the Cost-Effectiveness of Sample Size Maintanance Programs Revealed the Need to Consider Substitution Sampling. Journal of Clinical Epidemiology, 65: 1200-1211.
Feller, L., & Lemmer, J. (2012). New 'second primary' cancers. Journal of the South African Dental Association, 67(4): 175-178.
Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., . . . Bray, F. (2013). GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Retrieved from International Agency for Research on Cancer: http://globocan.iarc.fr, accessed on 6 July 2014
Filho, J. A., & Calil, S. J. (2000). Monte Carlo Simulation of Cost-Effectiveness Ratios. Proceedings of the 22"d Annual EMBS International Conference (pp. 595-598). Chicago: IEEE.
Foster, T. S., Miller, J. D., Boye, M. E., Blieden, M. B., Gidwani, R., & Russell, M. W. (2011). The Economic Burden of Metastatic Breast Cancer: A Systematic Review of Literature from Developed Countries. Cancer Treatment Reviews, 37: 405-415.
Foucher, Y., Giral, M., Soulillou, J.-P., & Daures, J.-P. (2007). A Semi-Markov Model for Multistate and Interval-Censored Data with Multiple Terminal Events: Application in Renal Transplantation. Statistics in Medicine, 26: 5381-5393.
Foucher, Y., Mathieu, E., Saint-Pierre, P., Durand, J.-F., & Daures, J.-P. (2005). A Semi-Markov Moel Based on Generalized Weibull Distribution with an Illustration for HIV Disease. Biometrical Journal, 47(6): 1-9.
Francisci, S., Tabroff, K. R., Gigli, A., Mariotto, A., Mezzetti, M., & Lipscomb, J. (2013). Advancing the Science of Cancer Cost Measurement: Challenges and Opportunities. Annali dell'Istituto Superiore di Sanita, 49(1): 73-78.
Goshu, A. T., & Dessie, Z. G. (2013). Modelling Progression of HIV/AIDS Disease Stages Using Semi-Markov Processes. Journal of Data Science, 11: 269-280.
Health Promotion Administration. (2014). Cancer Prevention and Control. Retrieved from http://www.hpa.gov.tw/Bhpnet/English/ClassShow.aspx?No=201401280006, accessed on 6 July 2014
Hsiao, F.-Y., Yang, C.-L., Huang, Y.-T., & Huang, W.-F. (2007). Using Taiwan's National Health Insurance Research Databases for Pharmacoepidemiology Research. Journal of Food and Drug Analysis, 15(2): 99-108.
Huang, W.-F., & Lai, I.-C. (2005). Patterns of Sleep-Related Medications Prescribed to Elderly Outpatients with Insomnia in Taiwan. Drugs Aging, 22: 957-965.
Huang, W.-F., Hsiao, F.-Y., & Tsai, Y.-W. (2006). Cardiovascular Events Associated with Long-Term Celecoxib, Rofecoxib, and Meloxicam Use in Taiwan: An Observational Study. Drug Safety, 29: 261-272.
Hwang, J., & Wang, J. (1999). Monte Carlo Estimation of Extrapolation of Quality-Adjusted Survival for Follow-Up Studies. Statistics in Medicine, 18: 1627-1640.
Kang, M.-H., & Lagakos, S. W. (2007). Statistical MEthods for Panel Data From a Semi-Markov Process, with Application to HPV. Biostatistics, 8(2): 252-264.
Kapetanakis, V., Matthews, F. E., & Van Den Hout, A. (2013). A Semi-Markov Model for Stroke with Piecewise-Constant Hazards in the Presence of Left, Right and Interval Censoring. Statistics in Medicine, 32: 697-713.
Katsaliaki, K., & Mustafee, N. (2011). Applications of Simulation Within the Healthcare Context. Journal of the Operational Research Society, 62: 1431-1451.
Kuntz, K., & Weinstein, M. (2001). Modelling in Economic Evaluation. In M. F. Drummond, & A. McGuire, Economic Evaluation in Health Care: Merging Theory with Practice (pp. 141-171). New York: Oxford University Press.
Lai, S.-W., Liao, K.-F., Chen, P.-C., Tsai, P.-Y., Hsieh, D. P., & Chen, C.-C. (2012). Antidiabetes Drugs Correlate With Decreased Risk of Lung Cancer: A Population-Based Obsevation in Taiwan. Clinical Lung Cancer, 13(2): 143-148.
Lang, H.-C., & Wu, S.-L. (2012). Lifetime Costs of The Top Five Cancers in Taiwan. The European Journal of Health Economics, 13: 347-353.
Lee, E. K., & Tseng, P. L. (2008). Retrospective Study on the Utilization and Cost of Immunosupressive Agents Among Kidney Transplant Recipients in Taiwan: A 5-Year Review. Transplantation Proceedings, 40(7): 2214-2217.
Li, T.-Y., Hsieh, J.-S., Lee, K.-T., Hou, M.-F., Wu, C.-L., Lao, H.-Y., & Shi, H.-Y. (2014). Cost Trend Analysis of Initial Cancer Treatment in Taiwan. PLoS One, 9(10): e108432.
Lipscomb, J., Weinstein, M. C., & Torrance, G. W. (1996). Time Preference. In M. Gold, J. Siegel, L. B. Russel, & M. C. Weinstein, Cost-Effectiveness in Health and Medicine. New York: Oxford.
Listwoń, A., & Saint-Pierre, P. (2013). SemiMarkov: An R Package fro Parametric Estimation in Multi-State Semi-Markov Models.
Listwon-Krol, A., & Saint-Pierre, P. (2014). Package 'SemiMarkov' Reference Manual. Retrieved from http://cran.r-project.org/web/packages/SemiMarkov/SemiMarkov.pdf
Listwoń-Krol, A., & Saint-Pierre, P. (2014). SemiMarkov: Multi-States Semi-Markov Models. R Package version 1.3.1, URL http://cran.r-project.org/web/packages/SemiMarkov/.
Mahadevan, S. (1997). Monte Carlo Simulation. In T. A. Cruse, Reliability-Based Mechanical Design (pp. 123-146). New York: CRC Press.
Masala, G., Cannas, G., & Micocci, M. (2014). Survival probabilities for HIV Infected Patients Through Semi-Markov Processes. Biometrical Letters, 51(1): 13-36.
Metropolis, N. (1987). The Beginning of the Monte Carlo Method. Los Alamos Science, 15(587): 125-130.
National Health Insurance Administration. (2012). 2012 National Health Insurance Statistics report. Taipei: National Health Insurance Administration.
National Health Insurance Administration. (2014). NHI Insurance Coverage 2014. Retrieved from National Health Insurance Administration Web Site: http://www.nhi.gov.tw/Resource/webdata/20517_2_201407_National%20Health%20Insurance%201.pdf, accessed on 1 August 2014
Park, Y.-S., Kim, S.-H., Park, S.-K., Park, B.-J., Kim, Y.-T., Lee, S.-M., . . . Yang, S.-C. (2010). Costs for 5-Year Lung Cancer Survivors in a Tertiary Care Hospital in South Korea. Lung Cancer, 299-304.
Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P. (2001). Estimating the world cancer burden: Globocan 2000. International Journal of Cancer, 94: 153-156.
R Core Team. (2014). R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. URL: http://www.R-project.org/.
Ray, M. R., & Jablons, D. M. (2010). Hallmarks of Metastasis. In V. Keshamouni, D. Arenberg, & G. Kalemkerian, Lung Cancer Metastasis (pp. 29-46). New York: Springer.
Riihimaki, M., Hemminki, A., Fallah, M., Thomsen, H., Sundquist, K., Sundquist, J., & Hemminki, K. (2014). Metastatic Sites and Survival in Lung Cancer. Lung Cancer, 86: 78-84.
Saint-Pierre, P., Combescure, C., Daures, J. P., & Godard, P. (2003). The Analysis of Asthma Control Under a Markov Assumption with Use of Covariates. Statistics in Medicine, 22: 3755-3770.
Schweitzer, T., Vince, G. H., Herbold, C., Roosen, K., & Tonn, J.-C. (2001). Extraneural Metastases of Primary Brain Tumors. Journal of Neuro-Oncology, 53: 107-114.
Shao, Y.-Y., Shau, W.-Y., Lin, Z.-Z., Chen, H.-M., Kuo, R., Yang, C.-H., & Lai, M.-S. (2013). Comparison of Gefitinib and Erlotinib Efficacies as Third-Line Therapy for Advanced Non-Small-Cell Lung Cancer. European Journal of Cancer, 49: 106-114.
Shih, Y.-C., Pan, I.-W., & Tsai, Y.-W. (2009). Information Technology Facilitates Cost-Effectiveness Analysis in Developing Countries: An Observational Study of Breast Cancer Chemotherapy in Taiwan. Pharmacoeconomics, 27(11): 947-961.
Silva, G. O., Ortega, E. M., & Cordeiro, G. M. (2010). The Beta Modified Weibull Distribution. Lifetime Data Analysis, 16: 409-430.
Smoll, N. R., & Villanueva, E. V. (2010). The Epidemiology of Extraneural Metastases From Primary Brain, Spinal Cord, and Meningeal Tumors. Neurosurgery, 67(5): E1470.
Song, X., Zhao, Z., Barber, B., Gregory, C., Cao, Z., & Gao, X. (2011). Cost of Illness in Patients with Metastatic Colorectal Cancer. Journal of Medical Economics, 14(1): 1-9.
Sonnenberg, F. A., & Beck, J. R. (1993). Markov Models in Medical Decision Making: A Practical Guide. Medical Decision Making, 13: 322-338.
TreeAge Pro (2014). http://www.treeage.com.
Uyl-de Groot, C. A., McDonell, J., Velde, G. T., Radice, D., & Groen, H. J. (2006). Cost-Effectiveness of Hypothetical New Cancer Drugs in Patients with advanced Small-Cell Lung Cancer: Results of a Markov Chain Model. Therapeutics and Clinical Risk Management, 2(3): 317-323.
Wahed, A. S., The, M. L., & Jeong, J.-H. (2009). A New Generalization of Weibull Distribution with Application to a Breast Cancer Data Set. Statistics in Medicine, 28(16): 2077-2094.
Weiss, G. H., & Zelen, M. (1965). A semi-Markov Model for Clinical Trials. Journal of Applied Probability, 2(2): 269-285.
Willan, A. R., Lin, D. Y., & Manca, A. (2005). Regression Methods for Cost-Effectiveness Analysis with Censored Data. Statistics in Medicine, 24: 131-145.
Wu, B., Chen, W.-F., Shen, J.-F., & Ye, M. (2011). Cost-Effectiveness of Adding Rh-Endostatin to First-Line Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer in China. CLinical Therapeutics, 33(10): 1446-1455.
Wu, C.-L., Yang, Y.-C., Huang, L.-M., & Chen, K.-T. (2009). Cost-Effectiveness of Childhood Rotavirus Vaccination in Taiwan. Vaccine, 27: 1492-1499.
Wu, C.-Y., Hu, H.-Y., Pu, C.-Y., Huang, N., Shen, H.-C., Li, C.-P., & Chou, Y.-J. (2010). Pulmonary Tuberculosis Increases the Risk of Lung Cancer: A Population-Based Cohort Study. Cancer, 618-623.
Xia, J.-H., Zeephongsekul, P., & Packer, D. (2010). Spatial and Temporal Modelling of Tourist Movements Using Semi-Markov Processes. Tourism Management, 1-8.
Yang, S.-C., Lai, W.-W., Su, W.-C., Wu, S.-Y., Chen, H.-W., Wu, Y.-L., . . . Wang, J.-D. (2013). Estimating the Lifelong Health Impact and Financial Burdens of Different Types of Lung Cancer. BMC Cancer, 13:579.
Zeng, X.-H., Li, J.-H., Peng, L.-B., Wang, Y.-H., Tan, C.-Q., Chen, G.-N., . . . Yi, L.-D. (2014). Economic Outcomes of Maintenance Gefitinib for Locally Advanced/Metastatic Non-Small-Cell Lung Cancer with Unkown EGFR Mutations: A Semi-Markov Model analysis. PLoS ONE, 9(2): 1-9.
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔