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基于延遲時(shí)間理論的疾病篩查策略研究

發(fā)布時(shí)間:2018-02-26 11:06

  本文關(guān)鍵詞: 延遲時(shí)間理論 疾病預(yù)防 篩查策略 風(fēng)險(xiǎn)分析 出處:《北京科技大學(xué)》2017年博士論文 論文類型:學(xué)位論文


【摘要】:篩查作為疾病預(yù)防的重要手段,主要是在健康或無明顯癥狀人群中實(shí)施定期篩查策略,從而實(shí)現(xiàn)對(duì)于疾病或風(fēng)險(xiǎn)的早期識(shí)別,促進(jìn)人類健康。國(guó)內(nèi)外各國(guó)對(duì)于少數(shù)幾種疾病已頒布了各自的篩查指南,然而大多數(shù)疾病的篩查策略仍存在很大爭(zhēng)議。因此,疾病篩查策略的制定和評(píng)估成為篩查研究中一個(gè)重要問題。篩查策略一般包括三個(gè)方面:篩查方法、篩查起止時(shí)間和篩查周期。選擇性篩查除這三個(gè)方面之外,還包括對(duì)高危風(fēng)險(xiǎn)人群的識(shí)別。本文針對(duì)目前整群篩查中的篩查策略的建模和選擇性篩查中疾病的風(fēng)險(xiǎn)評(píng)估研究中存在的不足,考慮延遲時(shí)間理論在建模方面的優(yōu)勢(shì),將其由設(shè)備的預(yù)防性維修領(lǐng)域擴(kuò)展到疾病的預(yù)防性篩查策略領(lǐng)域中。分別進(jìn)行了篩查周期、篩查方法和篩查周期、篩查起始時(shí)間和篩查周期、篩查人群方面的研究。(1)考慮篩查方法的不完美性和疾病的窗口期對(duì)于篩查結(jié)果的影響,以性傳播疾病為例,基于延遲時(shí)間理論建立了單篩查方法的情況下對(duì)篩查周期進(jìn)行優(yōu)化的成本模型。在成本中包括了篩查成本、與延遲診斷相關(guān)的治療成本和在感染后篩查前傳染其他人的成本。在算例研究中對(duì)模型的有效性進(jìn)行了驗(yàn)證,并通過模型優(yōu)化結(jié)果的比較和不完美篩查概率的敏感性分析,證明了窗口期和不完美篩查對(duì)篩查策略的期望總成本和篩查周期的影響。(2)考慮普通篩查方法和完美篩查方法在篩查的成本和篩查率上的差別,以癌癥為例,基于延遲時(shí)間理論分別建立了三種篩查方案下對(duì)篩查周期進(jìn)行優(yōu)化的成本模型。這三種篩查方案分別為只進(jìn)行普通篩查、只進(jìn)行全面篩查以及普通篩查與全面篩查相結(jié)合的方案?偝杀境税ㄆ胀êY查的成本、全面篩查的成本、癌癥檢出后與延遲診斷時(shí)間相關(guān)的治療成本,還包括了由于癌癥早死造成的壽命折損成本。利用具體算例對(duì)模型的有效性進(jìn)行了驗(yàn)證,并通過對(duì)三種篩查方案優(yōu)化結(jié)果的比較,表明了普通篩查與全面篩查相結(jié)合的篩查方案優(yōu)于只使用一種篩查方法的篩查方案。(3)考慮疾病發(fā)病率與年齡密切相關(guān)的特點(diǎn)以及人群中的知曉率和控制率較低的情況,以高血壓為例,基于延遲時(shí)間理論建立了對(duì)篩查起始時(shí)間和篩查周期進(jìn)行聯(lián)合優(yōu)化的兩階段檢出率模型和兩階段發(fā)病率模型。其中第一個(gè)階段為時(shí)間間隔較長(zhǎng)的一次性篩查,第二階段為第一次篩查后的時(shí)間間隔較短的重復(fù)性篩查。這樣第一階段的時(shí)間間隔即為篩查起始時(shí)間,第二階段的時(shí)間間隔為篩查周期。算例結(jié)果表明,相比于一階段的篩查策略,兩階段的篩查策略具有更低的成本,更好的效果。(4)考慮疾病風(fēng)險(xiǎn)因素在不同階段的作用、兩階段生存時(shí)間的相關(guān)性、延遲診斷以及非隨機(jī)刪失問題,以丙肝為例,基于延遲時(shí)間理論和生存分析方法,分別建立了隨機(jī)刪失和非隨機(jī)刪失情況下對(duì)風(fēng)險(xiǎn)因素進(jìn)行估計(jì)的兩階段生存時(shí)間模型。利用風(fēng)險(xiǎn)函數(shù)的改變,然后結(jié)合自助法和多重填補(bǔ)法,對(duì)非隨機(jī)刪失的數(shù)據(jù)進(jìn)行填補(bǔ)可以將不同程度的非隨機(jī)刪失影響納入到模型中。仿真研究表明當(dāng)兩階段生存時(shí)間是相關(guān)的、診斷存在延遲以及存在不同程度的非隨機(jī)刪失的情況下,在模型中忽略這些因素會(huì)使得風(fēng)險(xiǎn)因素的參數(shù)估計(jì)產(chǎn)生不可忽視的偏倚,從而導(dǎo)致對(duì)于高危風(fēng)險(xiǎn)人群的錯(cuò)誤識(shí)別和生存時(shí)間的錯(cuò)誤估計(jì)。通過以上研究,對(duì)延遲時(shí)間理論進(jìn)行了豐富和擴(kuò)展,將其由設(shè)備可靠性領(lǐng)域擴(kuò)展到人群健康領(lǐng)域,為疾病篩查策略的制定提供新的科學(xué)決策模型和方法,克服了以往研究的不足,對(duì)現(xiàn)有的疾病篩查研究的對(duì)象進(jìn)行擴(kuò)展,探討疾病篩查策略在多種類型疾病中的建模方法,篩查策略的優(yōu)化有利于實(shí)現(xiàn)疾病的早診斷、早發(fā)現(xiàn)、早治療,降低疾病的發(fā)病率,提高患者生存率,降低社會(huì)的醫(yī)療負(fù)擔(dān),提高人群的健康水平。
[Abstract]:As an important means of screening for disease prevention, mainly the implementation of regular screening strategies in health or no obvious symptoms of the crowd, so as to achieve early recognition for the disease or the risk, the promotion of human health. The domestic and foreign countries for a few diseases have enacted their own screening guidelines, however, remains controversial screening strategies for most diseases. Therefore, the formulation and evaluation of disease screening strategy has become an important problem in the study. Screening screening strategies generally include three aspects: screening, screening and screening time period. Selective screening in addition to these three aspects, including identification of high risk population. In this paper, aiming at the existing problems of research on risk assessment of disease modeling and selective screening screening strategies for the screening of the cluster in the consideration of delay time theory in modeling the advantages of the equipment Preventive maintenance areas extend to the field of preventive screening strategies were carried out. The disease screening cycle, screening methods and periodic screening, starting time and period of screening, screening research aspects. (1) considering the effect of screening method is not perfect and the window period for disease screening results, with sexual transmission the disease as an example, the delay time is established based on the theory of single screening method under the condition of cost optimization model for screening cycle. Based on the cost includes the cost of screening and treatment costs associated with delayed diagnosis and screening after infection infectious to others. In the calculation of the cost of the validity of the model in the study of cases verify, and through sensitivity analysis of optimization model and compare the results of imperfect screening probability, and proves the effect of the window period and imperfect screening for screening strategies of the expected total cost and cycle (screening. 2) consider different common screening methods and perfect screening methods in the cost of screening and screening rate, in cases of cancer, three screening methods were established respectively under the theory of delay time cost optimization model for screening. This cycle based on three screening methods were only conventional screening, only a comprehensive screening and the general screening and comprehensive screening combination scheme. The total cost including the cost of screening in general, comprehensive screening costs, treatment costs associated with delayed diagnosis time after detection of cancer, including life expectancy loss due to premature death. The cost of cancer using specific example the validity of the model was verified, and through comparison of three kinds of optimization results show that the scheme of screening, screening and screening screening scheme is better than ordinary comprehensive screening combined only using a screening method. (3) consider the disease Know the characteristics of disease rate is closely related to the age and the population rate and control rate are lower, with hypertension as an example, the delay time is established based on the theory of two stages of the joint optimization of screening starting time and period of screening detection rate model and two stage model based on the incidence rate. The first stage is a one-time screening time the second stage is long, repeated screening of the first screening after the time interval is short. So the first stage that is the time interval for screening the start time, the second phase of the time interval for screening period. The results show that the screening strategy compared to the stage, the two stage of the screening strategy has lower cost and better effect. (4) consider the disease risk factors in different stages, correlation with the survival time of the two phase, delayed diagnosis and non random censoring problem in C for example, base Yu Yanchi's theory of time and survival analysis method, were established for random censoring and survival time of the two stage model non random censoring of the risk factors were estimated. The risk function of the change, and then combined with the bootstrap method and multiple imputation method for non random censored data can fill the non random censoring effect different degree into the model. The simulation results show that when the two stage is related to the survival time, the delay of diagnosis, there are different degrees of non random censoring case, ignoring these factors will make the parameters of risk factors estimation bias can not be ignored in the model, which leads to error identification and survival the time people at high risk for error estimation. Through the above research, the delay time of theory to enrich and expand the field of equipment reliability, by extension to human health. The domain, to provide scientific decision-making model and new method for the development of disease screening strategies, to overcome the shortcomings of previous studies, objects of disease screening study of the existing modeling methods of extended disease screening strategies in various types of diseases, optimal screening strategy is conducive to the realization of the disease early diagnosis, early discovery, early treatment reduced the incidence of disease, improve the survival rate of patients, reduce the social burden of medical care, improve the health level of people.

【學(xué)位授予單位】:北京科技大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2017
【分類號(hào)】:R195.4

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