ABSTRACT
In the midst of epidemics such as COVID-19, therapeutic candidates are unlikely to be able to complete the usual multi-year clinical trial and regulatory approval process within the course of an outbreak. We apply a Bayesian adaptive patient-centered model--which minimizes the expected harm of false positives and false negatives--to optimize the clinical trial development path during such outbreaks. When the epidemic is more infectious and fatal, the Bayesian-optimal sample size in the clinical trial is lower and the optimal statistical significance level is higher. For COVID-19 (assuming a static R0 = 2 and initial infection percentage of 0.1%), the optimal significance level is 7.1% for a clinical trial of a non-vaccine anti-infective therapeutic clinical trial and 13.6% for that of a vaccine. For a dynamic R0 ranging from 2 to 4, the corresponding values are 14.4% and 26.4%, respectively. Our results illustrate the importance of adapting the clinical trial design and the regulatory approval process to the specific parameters and stage of the epidemic.
ABSTRACT
Objective To observe the adverse effects of passive smoking on antioxidant capacity and spermiogenesis of the testis and epididymides in rats.Methods SD rats were exposed to smoke in a self-made passive smoking chamber twice a day for 48 days.At the end of the experiment,the right testis and epididymides homogenate were prepared and the level of SOD,GSH-Px, NOS,NO and MDA were measured respectively.The sperms of left epididymides were observed by light microscope for determining sperm density,motility,progressive motility,fast progressive motility.The microstructure changes of left testis were observed.Results In passive smoking group,the level of MDA was significantly increased(P
