bear (BE/BA for R) v2.9.0

What bear can do:

This package includes three parts. The first is doing “sample size estimation.” Users can choose 80 or 90% power and defined upper BE acceptance criteria to conduct an ABE between these two formulations. Sample size also depends on the magnitude of variability. Variance estimates can be obtained from the biomedical literature or pilot studies. For crossover designs, we provide two kinds of methods for different data (raw and log-transformed) (Liu, et al. 1992; Hauschke, et al.1992). This function will provide information about how many numbers of subjects should be included. Second part is to perform NCA.  We provide NCA approach to compute AUC0-t, AUC0-inf and terminal elimination rate constant (λz) with time-Cp profile. λz, the terminal phase rate constant, will be estimated from the slope of linear regression with various approaches (manual selection of data points, adjusted R2 (ARS), AIC, Two-Times-Tmax (TTT), TTT-ARS, TTT-AIC, etc).  All these approaches do not include the data point of (Tmax, Cmax).  Linear trapezoidal rule is used to calculate AUC0-t (AUC from time 0 to the last measurable Cp).  The extrapolated AUC (from time of the last measurable Cp to infinity) will be estimated from the last measurable Cp divided by λz.  AUC0-inf (AUC from time 0 to infinity) equals to AUC0-t plus the extrapolated AUC(AUCt-inf).  Cmax is obtained from the observed time-Cp profile. All plots from NCA will be stored in a pdf file (like this pdf) and all reports, including NCA reports (like this NCA PK) and pharmacokinetic summaries (Cmax, Tmax, AUC0-t, AUC0-inf, AUC0-t/AUC0-inf*100%, ln(Cmax), ln(AUC0-t), ln(AUC0-inf), MRT0-inf, T1/2, Vd/F, λz, Cl/F). Please refer to some pharmacokinetic textbooks about how to calculate these parameters with NCA.  Final step is to perform ANOVA (lm in R). For non-replicated crossover designs, FDA guidance (FDA, 2001) recommends parametric procedures to analyze log-transformed BA measures. It continues to perform ANOVA and calculate 90%CIs, and finally to conclude if it is bioequivalent with three pivotal BE parameters. This package also supplies ANOVA stat reports (like this ANOVA stat) or results of linear mixed effects (lme_stat.txt for replicate or parallel BE studies) and summaries (like this statistical summaries). All results obtained from outlier detection analysis (now only for 2x2x2 crossover BE study) will also appear in ANOVA_stat, and all plots from outlier detection analysis will be stored in this ODplots.pdf.