Consolidated Coxian Phase-type-based Stochastic Model for Evaluation of Effectiveness of Population-based Screening

• Main Authors: Hsiao-Hsuan Jen, 任小萱
• Other Authors: 陳秀熙
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/8tjw2h

博士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 107 === Background Evaluation of efficacy and effectiveness of population-based organized service screening is more intractable but informative than that of population-based experimental and quasi-experimental program. In addition to lacking of an adequate control group, elucidating a constellation factors implicated in population-based service screening program, including structure in relation to coverage rate, process resulting from referral process and waiting time for confirmatory diagnosis, and outcomes pertaining to multi-state disease natural history is a complex process that requires a comprehensive mathematical model to quantify relative contributions of each factor to the effectiveness of screening. To this end, this thesis proposes the consolidated Coxian-phase type model in conjunction with Queue process to develop a novel mathematical model for evaluating the impact of three-aspect factors on the effectiveness of population-based service screening program. Aims The aims of thesis are therefore to (1) extend the previously proposed Queue process to model the arrival rate of eligible screenees by different settings of institution and geographic areas; (2) apply the Coxian-phase type process in conjunction with Hurdle regression model to estimate the compliance rate and different phases of waiting time for confirmatory diagnosis; (3) develop Coxian-phase Markov process and Semi-Markov process to elucidate and quantify the occult progression of multi-state disease process with the incorporation of AJCC tumour stage information; (4) consolidate two Coxian-phase type processes in (2) and (3) in conjunction with the Queue process as a unifying quantitative system of population-based screening model; and (5) project the effectiveness of population-based organized service screening program by changing various scenarios of underlying factors related to population-based organized service screening program. Data This thesis is motivated by population-based screening program for colorectal cancer (CRC) with biennial fecal immunochemical test (FIT) in Taiwan. A total of 5,417,699 eligible population (aged 50-69 years in 2004-2009) composed our study cohort. In 2004-2014, the program covered 56.6% (n=3,067,853) eligible population attending at least one FIT. The positive rate was 6.9% (n=211,531) in the first round. Among them, 59% (n=124,921) underwent confirmatory examination. Data on all screening history together with screening findings were prospectively collected in the central screening monitor system. A total of 88,730 subjects were detected as adenoma. There were 51,145 CRC diagnosed upon screening, including 9,396 and 4,941 screen-detected cases in the first and subsequent rounds of screen, respectively, 6,184 interval cancers, and 30,624 refusers among those never attended. Data on the distribution of AJCC staging were available. Methods To build up a unifying framework for modelling the whole process of population-based organized service screening, we began with the Queue process to capture the arrival rate of eligible screenees given hierarchical institute setting and geographic area. After the arrival of attending screening, we then applied the Coxian-phase type process in conjunction with Hurdle regression model to model the compliance and waiting time in relation to the referral process of confirmatory diagnosis for screen-positive subjects. Another Coxian-phase Markov process and Semi-Markov process was further developed to elucidate and quantify the occult progression of multi-state disease process with the incorporation of adenoma and AJCC tumour stage information. A series of simulation consolidating these two Coxian-phase type processes and the Queue process as a unifying quantitative system of population-based screening model was used to (1) elucidate the distribution of waiting time, and (2) project the effectiveness of population-based organized service screening program in terms of the reduction of advanced staged CRC with various scenarios of underlying factors related to population-based organized service screening program, including attendance rate, positive rate, and referral rate. Results 1. Projection related to coverage rate and referral process While the Queue process and the hurdle two-phase Coxian type model (abbreviated as QH-CPH model) were identified, the projection with the application of estimated parameters based on QH-CPH model indicates that if two-month waiting time is the maximum allowable clinical capacity, a three-year FIT screening program can be provided to cover 90% population given 7% positive rate, and 60% compliance rate. Other similar projections for the joint distribution of these parameters relevant to structure and process were derived in a similar manner. 2. Projected effectiveness of reducing advanced cancer We estimated the transition parameters governing the disease natural history modelled by a series of Coxian-phase type Markov process to project the following results on the effectiveness of reducing advanced cancer. (1) With parameters similar to the current situation (7% positive rate, and 60% referral rate), biennial screening with 50% coverage rate could yield the reduction of advanced CRC by 20%. (2) Compared with (1), the corresponding figures for 20%, 50%, 80%, and 100% coverage rate were 8%, 20%, 30%, and 36%, respectively, given 50% referral rate and 7% positive rate. (3) Compared with (1), the corresponding figures for 20%, 50%, 80%, and 100% referral rate were 7%, 18%, 26%, and 31%, respectively, given 50% coverage rate and 7% positive rate. (4) The effectiveness reduced with lower positive rate and longer inter-screening interval. Conclusion The consolidated Coxian-phase-type-based stochastic process was constructed in commensuration with a unifying framework of population-based organized service screening. Its relevant parameters governing the whole process from the arrival to the outcomes of disease status were estimated on the basis of Taiwanese biennial nationwide colorectal cancer screening program. It is very useful for projecting the performance in relation to structure and process of screening program and also play an important role in the projection of effectiveness of screening program such as the reduction of advanced cancer.