replicateBE (version 1.1.3)

TRR.RTR.RRT: Reference Datasets for TRR|RTR|RRT (partial) Replicate Designs

Description

Datasets from the public domain or simulated to be evaluated by method.A(), method.B(), or ABE().

Format

• Reference Dataset 02 24 subjects. Balanced (eight subjects in each of the three sequences) and complete (no missing data). No outliers. A data frame with 72 observations on the following 6 variables:

  rds02

  subject	a factor with 24 levels: 1, 2, …, 24
  period	a factor with 3 levels: 1, 2, 3
  sequence	a factor with 3 levels: TRR, RTR, RRT
  treatment	a factor with 2 levels: T, R
  PK	a numeric vector of pharmacokinetic responses acceptable for reference-scaling (generally )

  In the source evaluated by SAS v9.1 for ABEL. Reported results:

  SAS Proc GLM

  CVwR	11.2%
  PE	102.26% (Method A and B)

• Reference Dataset 04 Data set of Table II given by Patterson & Jones. 51 subjects. Balanced (17 subjects in each of the three sequences) and complete. No outliers. A data frame with 153 observations on the following 5 variables:

  rds04

  subject	a factor with 51 levels: 1, 2, …, 56
  period	a factor with 3 levels: 1, 2, 3
  sequence	a factor with 3 levels: TRR, RTR, RRT
  treatment	a factor with 2 levels: T, R

  In the source evaluated by SAS with the FDA<U+2019>s mixed effects model (termed Method C by the EMA; not compatible with the guideline). Reported results:

  SAS Proc MIXED

  CVwR	61%
  PE	137%

• Reference Dataset 07 Simulated with = = 35%, GMR 0.90. 360 subjects. Balanced (120 subjects in each of the three sequences) and complete. No outliers. A data frame with 1,080 observations on the following 5 variables:

  rds07

  subject	a factor with 360 levels: 1, 2, …, 360
  period	a factor with 3 levels: 1, 2, 3
  sequence	a factor with 3 levels: TRR, RTR, RRT
  treatment	a factor with 2 levels: T, R

• Reference Dataset 30 Simulated with heteroscedasticity (), GMR = 0.90. 12 subjects. 14 subjects. Imbalanced (six subjects in sequence TRR, five in RTR, and three RRT) and incomplete (two missings in sequences TRR and RTR and three in sequence RRT). Missings / period: 0/1, 0/2, 7/3. No outliers. A data frame with 35 observations on the following 5 variables:

  rds30

  subject	a factor with 14 levels: 1, 2, …, 39
  period	a factor with 3 levels: 1, 2, 3
  sequence	a factor with 3 levels: TRR, RTR, RRT
  treatment	a factor with 2 levels: T, R

Details

Dataset	N	(%)	Evaluation
rds02	24	<30	method.A(), method.B(), ABE()
rds04	51	>30	method.A(), method.B()
rds07	360	>30	method.A(), method.B()

References

European Medicines Agency. London, 21 September 2016. Annex I, Annex III.

Patterson SD, Jones B. Viewpoint: observations on scaled average bioequivalence. Pharm Stat. 2012; 11(1): 1--7. 10.1002/pst.498

Examples

# NOT RUN {
str(rds02)
row <- c(10:12, 1:3, 16:18)
rds02[row, ]
summary(rds02[2:6])
# }