A statistical investigation into noninferiority testing for two binomial proportions

Master of ScienceDepartment of StatisticsChristopher VahlIn clinical research, noninferiority trials are becoming an important tool for investigating whether a new treatment is useful. The outcome measured can be either continuous (e.g. blood pressure level), time-to-event (e.g. days until heart attack), or binary (e.g. death). Rather than showing that the new treatment is superior to an active control, i.e. standard drug or treatment already available, one tests whether the new treatment is not meaningfully worse than the active control. Here we consider a binary outcome such as success or failure following an intervention. Evaluation of the treatment relative to control becomes a comparison of two binomial proportions; without loss of generality it will be assumed the larger the probability of success for an intervention the better. Simulation studies under these assumptions were programmed over a variety of different sample sizes and true population proportions to determine the performance between asymptotic noninferiority methods based on calculations of risk differences (with and without a continuity correction), relative risks, and odds ratio from two independent samples. Investigation was done to compare type I error rates, power when true proportions were exactly the same, and power when the true proportion for treatment group was less than the control, but not meaningfully inferior. Simulation results indicate most analysis methods have comparable type I error rates; however, the method based on relative risk has higher power under most circumstances. Due to the ease of interpretation with the relative risk, its use is recommended for establishing noninferiority of a binomial proportion between 0.2 and 0.8

Reduced Translocation of Glyphosate and Dicamba in Combination Contributes to Poor Control of Kochia scoparia: Evidence of Herbicide Antagonism

Citation: Ou, Junjun, Curtis R. Thompson, Phillip W. Stahlman, Nicholas Bloedow, and Mithila Jugulam. “Reduced Translocation of Glyphosate and Dicamba in Combination Contributes to Poor Control of Kochia Scoparia : Evidence of Herbicide Antagonism.” Scientific Reports 8, no. 1 (March 28, 2018): 1–11. https://doi.org/10.1038/s41598-018-23742-3.Kochia scoparia is a troublesome weed across the Great Plains of North America. Glyphosate and dicamba have been used for decades to control K. scoparia. Due to extensive selection, glyphosate- and dicamba-resistant (GDR) K. scoparia have evolved in the USA. Herbicide mixtures are routinely used to improve weed control. Herbicide interactions if result in an antagonistic effect can significantly affect the management of weeds, such as K. scoparia. To uncover the interaction of glyphosate and dicamba when applied in combination in K. scoparia management the efficacies of different doses of glyphosate plus dicamba were evaluated under greenhouse and field conditions using GDR and a known glyphosate- and dicamba-susceptible (GDS) K. scoparia. The results of greenhouse and field studies suggest that the combination of glyphosate and dicamba application controlled GDS, but glyphosate alone provided a better control of GDR K. scoparia compared to glyphosate plus dicamba combinations. Furthermore, investigation of the basis of this response suggested glyphosate and dicamba interact antagonistically and consequently, the translocation of both herbicides was significantly reduced resulting in poor control of K. scoparia. Therefore, a combination of glyphosate plus dicamba may not be a viable option to control GDR K. scoparia

Effect of mouse antisera targeting the Phlebotomus papatasi midgut chitinase PpChit1 on sandfly physiology and fitness

In sandflies, the absence of the peritrophic matrix (PM) affects the rate of blood digestion. Also, the kinetics of PM secretion varies according to species. We previously characterised PpChit1, a midgut-specific chitinase secreted in Phlebotomus papatasi (PPIS) that is involved in the maturation of the PM and showed that antibodies against PpChit1 reduce the chitinolytic activity in the midgut of several sandfly species. Here, sandflies were fed on red blood cells reconstituted with naïve or anti-PpChit1 sera and assessed for fitness parameters that included blood digestion, oviposition onset, number of eggs laid, egg bouts, average number of eggs per bout and survival. In PPIS, anti-PpChit1 led to a one-day delay in the onset of egg laying, with flies surviving three days longer compared to the control group. Anti-PpChit1 also had a negative effect on overall ability of flies to lay eggs, as several gravid females from all three species were unable to lay any eggs despite having lived longer than control flies. Whereas the longer survival might be associated with improved haeme scavenging ability by the PM, the inability of females to lay eggs is possibly linked to changes in PM permeability affecting nutrient absorption