本文選題：臨床隨訪研究　切入點(diǎn)：刪失率　出處：《南京醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景與目的:臨床隨訪研究中以生存時(shí)間作為主要療效指標(biāo)較為常見(jiàn),而數(shù)據(jù)刪失是生存資料的重要特征之一。有研究表明,過(guò)高的刪失率將導(dǎo)致療效估計(jì)偏差,檢驗(yàn)效能降低。實(shí)際研究中,往往組間的刪失率水平不同,有時(shí)還相差較大,這種情況下對(duì)療效評(píng)價(jià)產(chǎn)生何種影響尚無(wú)定論。此外,很多臨床試驗(yàn)中觀察的事件(例如腫瘤研究中發(fā)生進(jìn)展)只有在訪視時(shí)才能發(fā)現(xiàn),因此,并不知道準(zhǔn)確的事件發(fā)生時(shí)間,即區(qū)間刪失。本文主要探討臨床試驗(yàn)中這兩個(gè)問(wèn)題:(1)組間不同刪失率情況下常規(guī)療效評(píng)價(jià)方法的統(tǒng)計(jì)學(xué)性質(zhì),(2)區(qū)間刪失時(shí),生存時(shí)間的不同定義方法對(duì)參數(shù)估計(jì)結(jié)果的影響。方法:采用Monte-Carlo模擬方法,基于指數(shù)分布和Weibull分布分別產(chǎn)生生存時(shí)間,在不同情況下,分別采用log-rank檢驗(yàn)及Cox比例風(fēng)險(xiǎn)回歸模型進(jìn)行相應(yīng)的參數(shù)估計(jì)和組間療效的比較。論文分為兩個(gè)部分,第一部分:在組間刪失率相同和不同時(shí),從假設(shè)檢驗(yàn)的一類(lèi)錯(cuò)誤和檢驗(yàn)效能、參數(shù)估計(jì)的準(zhǔn)確度估計(jì)偏差等三個(gè)方面來(lái)評(píng)價(jià)對(duì)療效評(píng)價(jià)的影響;第二部分:區(qū)間刪失時(shí),事件發(fā)生時(shí)間不確定,比較3種不同的生存時(shí)間的定義方法,對(duì)中位生存時(shí)間和風(fēng)險(xiǎn)比估計(jì)的影響。結(jié)果:1)在生存分析中,刪失率的變化,會(huì)導(dǎo)致第一類(lèi)錯(cuò)誤率變化,且隨刪失率的增大,檢驗(yàn)效能逐漸下降;2)相比于兩組刪失率相等的情況,兩組刪失率不等時(shí),一類(lèi)錯(cuò)誤增加,HR的偏倚增大;且兩組刪失率相差越大,第一類(lèi)錯(cuò)誤率越大,檢驗(yàn)的結(jié)果越不可信。3)區(qū)間刪失時(shí),生存時(shí)間的不同定義對(duì)中位生存時(shí)間有影響,在隨訪間隔不是很大時(shí),對(duì)中位生存時(shí)間之差以及HR的估計(jì)影響不大。4)采用Cox比例風(fēng)險(xiǎn)回歸模型進(jìn)行療效評(píng)價(jià)時(shí),所得結(jié)果與log-rank檢驗(yàn)相似。結(jié)論:1)臨床隨訪研究中,總刪失率應(yīng)控制在30%以?xún)?nèi),組間刪失率之差應(yīng)控制在10%以?xún)?nèi),否則將導(dǎo)致一類(lèi)錯(cuò)誤膨脹。2)區(qū)間刪失時(shí),事件發(fā)生時(shí)間不確定,應(yīng)盡可能縮短每次訪視的時(shí)間,無(wú)論采用何種生存時(shí)間定義,不宜估計(jì)各組的中位生存時(shí)間,但估計(jì)中位生存時(shí)間之差或HR是可行的。
[Abstract]:Background & objective: survival time is common in clinical follow-up studies, and data deletion is one of the important characteristics of survival data. Test effectiveness is reduced. In actual studies, the level of deletion rate is often different among groups, and sometimes there is a big difference. In this case, the impact on the evaluation of curative effect has not been decided. The events observed in many clinical trials (such as progress in cancer studies) can only be detected during the visit, so the exact time of the event is not known. This paper mainly discusses the statistical properties of the conventional evaluation methods of curative effect under different deletion rates in clinical trials. Methods: Monte-Carlo simulation method is used to generate survival time based on exponential distribution and Weibull distribution respectively. Log-rank test and Cox proportional risk regression model were used to estimate the parameters and compare the efficacy of the two groups. The effect of hypothesis test on the evaluation of efficacy is evaluated from three aspects: the error of hypothesis test and the efficiency of test, the error of estimating accuracy of parameter estimation, etc. The second part: when the interval is censored, the time of event occurrence is uncertain. The effects of three different definition methods of survival time on median survival time and risk ratio estimation were compared. Results: in survival analysis, the change of deletion rate will lead to the change of error rate of the first kind, and increase with the increase of deletion rate. Compared with the two groups with the same deletion rate, the bias of HR increased when the deletion rate of two groups was not equal, and the greater the difference between the two groups, the greater the error rate of the first group. The less reliable. 3) interval deleted, the different definitions of survival time had an effect on median survival time, and when the interval of follow-up was not very large, The difference of median survival time and the estimated impact of HR. 4) when the Cox proportional risk regression model was used to evaluate the efficacy, the results were similar to that of the log-rank test. Conclusion: in the clinical follow-up study, the total deletion rate should be controlled within 30%. The difference of deletion rate between groups should be controlled within 10%, otherwise it will cause a class of errors to expand. 2) when the time of occurrence is uncertain, the time of each visit should be shortened as far as possible, no matter what definition of survival time is used. It is not suitable to estimate the median survival time of each group, but it is feasible to estimate the difference of median survival time or HR.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R195.1

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