In this paper we examine several definitions of vaccine efficacy(VE)that we found in the literature,for diseases that express themselves in outbreaks,that is,when the force of infection grows in time,reaches a maximum...In this paper we examine several definitions of vaccine efficacy(VE)that we found in the literature,for diseases that express themselves in outbreaks,that is,when the force of infection grows in time,reaches a maximum and then vanishes.The fact that the disease occurs in outbreaks results in several problems that we analyse.We propose a mathematical model that allows the calculation of VE for several scenarios.Vaccine trials usually needs a large number of volunteers that must be enrolled.Ideally,all volunteers should be enrolled in approximately the same time,but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function(for example,a Gaussian function).The outbreak can also be replaced by a continuous density function,and the use of these density functions simplifies the calculations.Assuming,for example Gaussian functions,one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time.The model allows us to conclude:First,the calculated vaccine efficacy decreases when the force of infection increases;Second,the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases;Third,different trial protocols can be simulated with this model;different vaccine efficacy definitions can be calculated and in our simulations,all result are approximately the same.The final,and perhaps most important conclusion of our model,is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort,or apply the Cox proportional hazards model for each cohort.展开更多
基金partially supported by Fundacao Butantan and CNPq.
文摘In this paper we examine several definitions of vaccine efficacy(VE)that we found in the literature,for diseases that express themselves in outbreaks,that is,when the force of infection grows in time,reaches a maximum and then vanishes.The fact that the disease occurs in outbreaks results in several problems that we analyse.We propose a mathematical model that allows the calculation of VE for several scenarios.Vaccine trials usually needs a large number of volunteers that must be enrolled.Ideally,all volunteers should be enrolled in approximately the same time,but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function(for example,a Gaussian function).The outbreak can also be replaced by a continuous density function,and the use of these density functions simplifies the calculations.Assuming,for example Gaussian functions,one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time.The model allows us to conclude:First,the calculated vaccine efficacy decreases when the force of infection increases;Second,the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases;Third,different trial protocols can be simulated with this model;different vaccine efficacy definitions can be calculated and in our simulations,all result are approximately the same.The final,and perhaps most important conclusion of our model,is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort,or apply the Cox proportional hazards model for each cohort.
