Application and comparison of test-negative design and its derivative design in vaccine clinical studies
SHU Ting
ZENG Xiangyan
FENG Junling
WANG Ling
Abstract：Objective To compare the advantages and disadvantages of two observational studies,test-negative design(TND)and its derivative designs to assess the evaluation methods of vaccine effectiveness(VE)in the real world.Methods Using Monte Carlo simulation method and Poisson regression model,by setting the flu-like infection rate,vaccination rate,unvaccinated incidence,true VE,and sensitivity(Se)and specificity(Sp)of different levels of combination,the mean VE,bias value,interval estimation and coverage rate of confidence interval of each research method were calculated to compare the simulation results.Results Four designs overestimated VE when Se and Sp were both 1,but with the decrease of Se and Sp,the difference between their estimated values and the true VE became greater,and Sp performed more significantly than Se.Conclusion Compared with other research designs,TND with the advantage of reducing medical treatment behavior confusions is more suitable for VE evaluation,and its derivative design also improves the accuracy of VE evaluation to a certain extent.However,it is still necessary to consider the influence of time-dependent factors to improve TND in order to evaluate the long-term VE.
Keywords：vaccine effectivenessobservational studyreal-time test-negative designcluster-randomized test-negative design
Publication Date：2026-05-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 707-713 )