基于延迟时间理论的疾病筛查策略研究

发布时间：2018-02-26 11:06

本文关键词： 延迟时间理论疾病预防筛查策略风险分析　出处：《北京科技大学》2017年博士论文　论文类型：学位论文

【摘要】：筛查作为疾病预防的重要手段,主要是在健康或无明显症状人群中实施定期筛查策略,从而实现对于疾病或风险的早期识别,促进人类健康。国内外各国对于少数几种疾病已颁布了各自的筛查指南,然而大多数疾病的筛查策略仍存在很大争议。因此,疾病筛查策略的制定和评估成为筛查研究中一个重要问题。筛查策略一般包括三个方面:筛查方法、筛查起止时间和筛查周期。选择性筛查除这三个方面之外,还包括对高危风险人群的识别。本文针对目前整群筛查中的筛查策略的建模和选择性筛查中疾病的风险评估研究中存在的不足,考虑延迟时间理论在建模方面的优势,将其由设备的预防性维修领域扩展到疾病的预防性筛查策略领域中。分别进行了筛查周期、筛查方法和筛查周期、筛查起始时间和筛查周期、筛查人群方面的研究。(1)考虑筛查方法的不完美性和疾病的窗口期对于筛查结果的影响,以性传播疾病为例,基于延迟时间理论建立了单筛查方法的情况下对筛查周期进行优化的成本模型。在成本中包括了筛查成本、与延迟诊断相关的治疗成本和在感染后筛查前传染其他人的成本。在算例研究中对模型的有效性进行了验证,并通过模型优化结果的比较和不完美筛查概率的敏感性分析,证明了窗口期和不完美筛查对筛查策略的期望总成本和筛查周期的影响。(2)考虑普通筛查方法和完美筛查方法在筛查的成本和筛查率上的差别,以癌症为例,基于延迟时间理论分别建立了三种筛查方案下对筛查周期进行优化的成本模型。这三种筛查方案分别为只进行普通筛查、只进行全面筛查以及普通筛查与全面筛查相结合的方案。总成本除了包括普通筛查的成本、全面筛查的成本、癌症检出后与延迟诊断时间相关的治疗成本,还包括了由于癌症早死造成的寿命折损成本。利用具体算例对模型的有效性进行了验证,并通过对三种筛查方案优化结果的比较,表明了普通筛查与全面筛查相结合的筛查方案优于只使用一种筛查方法的筛查方案。(3)考虑疾病发病率与年龄密切相关的特点以及人群中的知晓率和控制率较低的情况,以高血压为例,基于延迟时间理论建立了对筛查起始时间和筛查周期进行联合优化的两阶段检出率模型和两阶段发病率模型。其中第一个阶段为时间间隔较长的一次性筛查,第二阶段为第一次筛查后的时间间隔较短的重复性筛查。这样第一阶段的时间间隔即为筛查起始时间,第二阶段的时间间隔为筛查周期。算例结果表明,相比于一阶段的筛查策略,两阶段的筛查策略具有更低的成本,更好的效果。(4)考虑疾病风险因素在不同阶段的作用、两阶段生存时间的相关性、延迟诊断以及非随机删失问题,以丙肝为例,基于延迟时间理论和生存分析方法,分别建立了随机删失和非随机删失情况下对风险因素进行估计的两阶段生存时间模型。利用风险函数的改变,然后结合自助法和多重填补法,对非随机删失的数据进行填补可以将不同程度的非随机删失影响纳入到模型中。仿真研究表明当两阶段生存时间是相关的、诊断存在延迟以及存在不同程度的非随机删失的情况下,在模型中忽略这些因素会使得风险因素的参数估计产生不可忽视的偏倚,从而导致对于高危风险人群的错误识别和生存时间的错误估计。通过以上研究,对延迟时间理论进行了丰富和扩展,将其由设备可靠性领域扩展到人群健康领域,为疾病筛查策略的制定提供新的科学决策模型和方法,克服了以往研究的不足,对现有的疾病筛查研究的对象进行扩展,探讨疾病筛查策略在多种类型疾病中的建模方法,筛查策略的优化有利于实现疾病的早诊断、早发现、早治疗,降低疾病的发病率,提高患者生存率,降低社会的医疗负担,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.

【学位授予单位】：北京科技大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R195.4

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