TRRT.RTTR {replicateBE}

Reference Datasets for TRRT|RTTR Replicate Designs

Description

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

Format

• Reference Dataset 05
  26 subjects.
  Balanced (13 subjects in both sequences) and complete. No outliers.
  A data frame with 104 observations on the following 5 variables:

  rds05

  subject	a factor with 26 levels: 1, 2, ..., 26
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRRT, RTTR
  treatment	a factor with 2 levels: T, R
  PK	a numeric vector of pharmacokinetic responses (here Cmax)

  In the source evaluated by SAS with the FDA’s mixed effects model (termed ‘Method C’ by the EMA; not compatible with the guideline). Reported results:

  SAS Proc Mixed

  CVwR	5.47%
  CVwT	6.75%
  PE	107.90%
  90% CI	103.66% – 112.2%

• Reference Dataset 11
  37 subjects.
  Unbalanced (18 subjects in sequence TRRT and 19 subjects in RTTR) and complete. No outliers.
  A data frame with 148 observations on the following 5 variables

  rds11

  subject	a factor with 37 levels: 1, 2, ..., 37
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRRT, RTTR
  treatment	a factor with 2 levels: T, R
  PK	a numeric vector of pharmacokinetic responses (here Cmax)

  In the source evaluated by SAS with the FDA’s mixed effects model (termed ‘Method C’ by the EMA; not compatible with the guideline). Reported results:

  SAS Proc MIXED

  PE	90.0%
  90% CI	79.6% – 101.7%

• Reference Dataset 16
  38 subjects.
  Unbalanced (18 subjects in sequence TRRT and 20 in RTTR) and complete. No outliers.
  A data frame with 152 observations on the following 5 variables:

  rds16

  subject	a factor with 38 levels: 1, 2, ..., 38
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRRT, RTTR
  treatment	a factor with 2 levels: T, R
  PK	a numeric vector of pharmacokinetic responses (here Cmax)

Details

Dataset	N	CVwR (%)	Evaluation
rds05	26	<30	method.A(), method.B(), ABE()
rds11	37	>30	method.A(), method.B()
rds16	38	>30	method.A(), method.B()

Note

In software sequences and treatments are ranked in lexical order. Hence, executing str() or summary() will show sequence as "RTTR", "TRRT" and treatment as "R", "T". In BE – by convention – sequences are ordered with T first. The package follows this convention.

Source

Dataset	Origin	Description
rds05	Shumaker & Metzler	Cmax data given in the Appendix.
rds11	Hauschke et al.	Cmax data given in Table 9.6.
rds16	FDA, CDER	Cmax data of Drug 14a.

References

Shumaker RC, Metzler CM. The Phenytoin Trial is a Case Study of ‘Individual’ Bioequivalence. Drug Inf J. 1998; 32(4): 1063–72. doi:10.1177/009286159803200426

Hauschke D, Steinijans VW, Pigeot I. Bioequivalence Studies in Drug Development. Chichester: John Wiley; 2007. p216.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Bioequivalence Studies. Rockville, 1997. bioequivalence study files (archived 2017-07-23)

Examples

str(rds05)
summary(rds05[2:5])
head(rds11, 8)