Article(id=1241067202502250927, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202411070, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1730908800000, receivedDateStr=2024-11-07, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773823078989, onlineDateStr=2026-03-18, pubDate=1741536000000, pubDateStr=2025-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773823078989, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773823078989, creator=13701087609, updateTime=1773823078989, updator=13701087609, issue=Issue{id=1241067197318091153, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='5', pageStart='769', pageEnd='960', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773823077754, creator=13701087609, updateTime=1773823268053, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241067995544482681, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241067995544482682, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=931, endPage=937, ext={EN=ArticleExt(id=1241067203227865556, articleId=1241067202502250927, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Research design for evaluating long-term vaccine effectiveness based on extended test-negative design under fixed study duration model, columnId=1228016573156360233, journalTitle=Modern Preventive Medicine, columnName=Disease Control and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective To explore a suitable research design for evaluating the long-term effects of vaccines, taking into account the heterogeneity caused by individual susceptibility, vaccination status, vaccination timing, and the confounding effects of healthcare-seeking behavior.
Methods This study employed a Monte Carlo simulation method to extend the Test-Negative Design (TND),considering constant vaccine efficacy and two types of time-dependent vaccine efficacy under a fixed study duration model. A multivariable logistic regression model and a semi-parametric generalized additive model based on restricted cubic splines were constructed to evaluate the long-term effects of vaccines.
Results When only considering changes in vaccine efficacy, the estimated vaccine effectiveness (VE) curves from both models accurately fit the actual decay trend of VE, being only slightly higher than the true VE (approximately 1%-3%). The VE curves were minimally affected by vaccination rates, the mean probability of influenza-like illness in the entire population, and the probability of influenza-like illness in the vaccinated population.
Conclusion The extended TND under a fixed study duration model provides a feasible new approach for evaluating long-term vaccine effectiveness, with the potential for application to other types of vaccines. Both models demonstrated good fitting performance over time with no significant differences. However, further exploration is needed to comprehensively consider other heterogeneous influencing factors and to conduct simulation experiments with the extended TND after group assignment.
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目的 考虑个体易感性、接种状态、接种时间等因素导致的异质性以及就医行为混杂对疫苗长期效果评价的影响,探究适合评价疫苗长期效果的研究设计。
方法 本研究采用蒙特卡洛模拟法,对检测阴性设计(test-negative design, TND)进行扩展,在固定研究时长模式下考虑恒定疫苗效力和两种时依疫苗效力,构建基于时间限制性样条的多元logistic回归模型和半参数广义加性模型,评价疫苗长期效果。
结果 仅考虑疫苗效力变化时,两模型估计的疫苗有效性(vaccine effectiveness, VE)变化曲线均能较准确地拟合真实VE的衰减趋势,仅略高于真实VE(约1%~3%)。VE变化曲线受接种率、全人群流感样概率均值和已接种人群流感样概率的影响较小。
结论 固定研究时长模式下的扩展TND研究为评价疫苗长期效果提供了一个具有可行性的新思路,以期推广至其他种类的疫苗。两模型随时间变化的拟合效果较好且无明显差异。但未全面考虑其他异质性影响因素以及加入转组后的扩展TND的模拟实验,需进一步探索研究。
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1.空军军医大学军事预防医学系卫生统计学教研室,陕西 西安 710032)]), AuthorCompany(id=1241067207698993846, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, xref=2., ext=[AuthorCompanyExt(id=1241067207719965371, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, companyId=1241067207698993846, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=
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3.空军军医大学特殊作业环境危害评估与防治教育部重点实验室,陕西 西安 710032)])], figs=[ArticleFig(id=1241067212300145653, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 1, caption=
Schematic diagram of extended TND evaluation of vaccine effectiveness, figureFileSmall=1zbzFdErrGm4OuxVs6qAQw==, figureFileBig=UX1e1KD1VDrQ3AP1n9xBZg==, tableContent=null), ArticleFig(id=1241067215601062912, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图1, caption=
扩展TND评价疫苗效果示意图注:图A为TND和扩展TND示意图;图B为固定研究时长模式下的扩展TND时间-人数示意图。
, figureFileSmall=1zbzFdErrGm4OuxVs6qAQw==, figureFileBig=UX1e1KD1VDrQ3AP1n9xBZg==, tableContent=null), ArticleFig(id=1241067215869497374, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 2, caption=
Constant and time-dependent vaccine efficacy during 210 days, figureFileSmall=7FNer2NUgaJrLktSoKtkRA==, figureFileBig=RsgsMsGXi9HFFdXF+biDDA==, tableContent=null), ArticleFig(id=1241067216012103718, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图2, caption=
210 d内恒定和两种时依性的疫苗效力, figureFileSmall=7FNer2NUgaJrLktSoKtkRA==, figureFileBig=RsgsMsGXi9HFFdXF+biDDA==, tableContent=null), ArticleFig(id=1241067216121155634, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 3, caption=
Simulation flow chart, figureFileSmall=oiyvX3eux5ekAIU2+HM1Gg==, figureFileBig=4Yo5UjfL/y2Qv0oJlTRvWg==, tableContent=null), ArticleFig(id=1241067216276344889, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图3, caption=
模拟流程图, figureFileSmall=oiyvX3eux5ekAIU2+HM1Gg==, figureFileBig=4Yo5UjfL/y2Qv0oJlTRvWg==, tableContent=null), ArticleFig(id=1241067216410562625, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 4, caption=
Change curve of VE under constant 70% vaccine efficacy mode, figureFileSmall=eI/CQNEvh30gh0+MslaF5Q==, figureFileBig=PoTezMr6aYUxa14yqPAe0w==, tableContent=null), ArticleFig(id=1241067216553168972, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图4, caption=
疫苗效力为恒定70%模式下VE变化曲线图注:图A Vcover=30%, ILL1=30%, ILL2=30%;图B Vcover=50%, ILL1=30%, ILL2=70%;图C Vcover=50%, ILL1=50%, ILL2=50%;gam表示基于时间限制性样条的多元logistic回归模型绘制的VE衰减曲线;logit表示根据半参数广义加性模型绘制的VE衰减曲线;pVE表示接种完成后VE衰减曲线;rVE表示在全人群中的VE衰减曲线;rVE_OR表示根据TND算法绘制的VE衰减曲线。
, figureFileSmall=eI/CQNEvh30gh0+MslaF5Q==, figureFileBig=PoTezMr6aYUxa14yqPAe0w==, tableContent=null), ArticleFig(id=1241067216666415190, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 5, caption=
Change curve of VE in linear decline mode of vaccine efficacy, figureFileSmall=yEiTee5HJWli5NchDj+nHA==, figureFileBig=AIIo9WVEdOG/XEoH6o+gnQ==, tableContent=null), ArticleFig(id=1241067216758689886, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图5, caption=
疫苗效力为线性衰减模式下VE变化曲线图注:图A Vcover=30%, ILL1=30%, ILL2=58.6%;图B Vcover=50%, ILL1=30%, ILL2=70%;gam、logit、pVE、rVE、rVE_OR注释见图4。
, figureFileSmall=yEiTee5HJWli5NchDj+nHA==, figureFileBig=AIIo9WVEdOG/XEoH6o+gnQ==, tableContent=null), ArticleFig(id=1241067216871936105, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Figure 6, caption=
Change curve of VE in exponential decline mode of vaccine efficacy, figureFileSmall=PXYZ7Asv8CdZfWxqUFWolw==, figureFileBig=AAKjBkDPK09QRD31XbzIzw==, tableContent=null), ArticleFig(id=1241067217006153843, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=图6, caption=
疫苗效力为指数衰减模式下VE变化曲线图注:图A Vcover=30%, ILL1=30%, ILL2=58.6%;图B Vcover=50%, ILL1=30%, ILL2=70%;gam、logit、pVE、rVE、rVE_OR注释见图4。
, figureFileSmall=PXYZ7Asv8CdZfWxqUFWolw==, figureFileBig=AAKjBkDPK09QRD31XbzIzw==, tableContent=null), ArticleFig(id=1241067217106817149, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=EN, label=Table 1, caption=
Parameter settings and values
, figureFileSmall=null, figureFileBig=null, tableContent=
| 参数名称 | 符号 | 参数取值 |
|---|
| 总人群接种率 | vcover | 10%、30%、50%、60% |
| 研究样本量 | n | 10 000 |
| 疫苗有效性(初始值) | rVE | 随时间衰减(70%) |
| 未接种人群感染率 | AR1 | 15% |
| 脱落率 | Dp | 1% |
| 已接种人群感染率 | AR2 | AR1*(1-rVE) |
| 全人群流感样概率均值 | ILL | 30%、50%、70% |
| 已接种人群流感样率 | ILL1 | 10%、30%、50% |
| 未接种人群流感样率 | ILL2 |  |
), ArticleFig(id=1241067217241034891, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067202502250927, language=CN, label=表1, caption=
参数设置及取值
, figureFileSmall=null, figureFileBig=null, tableContent=
| 参数名称 | 符号 | 参数取值 |
|---|
| 总人群接种率 | vcover | 10%、30%、50%、60% |
| 研究样本量 | n | 10 000 |
| 疫苗有效性(初始值) | rVE | 随时间衰减(70%) |
| 未接种人群感染率 | AR1 | 15% |
| 脱落率 | Dp | 1% |
| 已接种人群感染率 | AR2 | AR1*(1-rVE) |
| 全人群流感样概率均值 | ILL | 30%、50%、70% |
| 已接种人群流感样率 | ILL1 | 10%、30%、50% |
| 未接种人群流感样率 | ILL2 |  |
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