Summary
The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data.
Considering numerical simulations, this study shows that the so-called vertical social distancing health policy is ineffective to contain the COVID-19 pandemic. We present the SEIR-Net model, for a network of social group interactions, as a development of the classic mathematical model of SEIR epidemics (Susceptible-Exposed-Infected (symptomatic and asymptomatic)-Removed). In the SEIR-Net model, we can simulate social contacts between groups divided by age groups and analyze different strategies of social distancing. In the vertical distancing policy, only older people are distanced, whereas in the horizontal distancing policy all age groups adhere to social distancing. These two scenarios are compared to a control scenario in which no intervention is made to distance people. The vertical distancing scenario is almost as bad as the control, both in terms of people infected and in the acceleration of cases. On the other hand, horizontal distancing, if applied with the same intensity in all age groups, significantly reduces the total infected people “flattening the disease growth curve”. Our analysis considers the city of Belo Horizonte, Minas Gerais State, Brazil, but similar conclusions apply to other cities as well. Code implementation of the model in R-language is provided in the supplementary material.
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