replicateBE (version 1.1.3)

TRTR.RTRT: Reference Datasets for TRTR|RTRT Designs

Description

Datasets from the public domain, edited, or obtained by simulations to be evaluated by method.A() and/or method.B().

Format

• Reference dataset 01 77 subjects. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (seven missings in sequence TRTR and three in sequence RTRT). Missings / period: 0/1, 1/2, 7/3, 2/4. Two outliers (subjects 45 and 52) in sequence RTRT. A data frame with 298 observations on the following 6 variables:

  rds01

  subject	a factor with 77 levels: 1, 2, …, 78
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  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: % 2.1.1 Text between or after list items is discouraged.

  SAS Proc GLM

  CVwR	47.0%
  PE	115.66% (Method A)
  	115.73% (Method B)
  90% CI	107.11% <U+2013> 124.89% (Method A)

• Reference dataset 06 Based on rds01. 77 subjects. Responses of T and R switched. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (seven missings in sequence TRTR and three in sequence RTRT). Missings / period: 0/1, 1/2, 7/3, 2/4. No outliers. A data frame with 298 observations on the following 6 variables:

  rds06

  subject	a factor with 77 levels: 1, 2, …, 78
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 08 Simulated with slight heteroscedasticity ( = 70%, = 80%), = = 150%, GMR = 0.85. 222 subjects. Balanced (222 subjects in both sequences) and complete. No outliers. The extreme sample size results from high variability, an assumed true GMR 0.85, and target power 90%. A data frame with 888 observations on the following 5 variables:

  rds08

  subject	a factor with 222 levels: 1, 2, …, 222
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 09 Based on rds08. Wide numeric range (data of last 37 subjects multiplied by 1,000,000). 222 subjects. Balanced (222 subjects in both sequences) and complete. No outliers. A data frame with 888 observations on the following 5 variables:

  rds09

  subject	a factor with 222 levels: 1, 2, …, 222
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 12 Simulated with extreme intra- and intersubject variability, GMR = 1.6487. 77 subjects. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (seven missings in sequence TRTR and three in sequence RTRT). Missings / period: 0/1, 1/2, 7/3, 2/4. No outliers. A data frame with 298 observations on the following 6 variables:

  rds12

  subject	a factor with 77 levels: 1, 2, …, 78
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 13 Based on rds08. Highly incomplete (approx. 50% of period 4 data deleted). 222 subjects. Balanced (111 subjects in both sequences) and incomplete (56 missings in both sequences). Missings / period: 0/0, 0/0, 0/0, 112/4. No outliers. A data frame with 776 observations on the following 5 variables:

  rds13

  subject	a factor with 222 levels: 1, 2, …, 222
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 14 Simulated with high variability, GMR = 1. Dropouts as a hazard function growing with period. 77 subjects. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (18 missings in sequence TRTR and 17 in sequence RTRT). Missings / period: 0/1, 4/2, 12/3, 19/4. No outliers. A data frame with 273 observations on the following 6 variables:

  rds14

  subject	a factor with 77 levels: 1, 2, …, 78
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 15 Based on ref08. Highly incomplete (approx. 50% of period 4 data coded as missing 'NA'). 222 subjects. Balanced (111 subjects in both sequences) and incomplete (56 missings in both sequences). Missings / period: 0/1, 0/2, 0/3, 112/4. No outliers. A data frame with 888 observations (112 NA) on the following 5 variables

  rds15

  subject	a factor with 222 levels: 1, 2, …, 222
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 18 Data set based on rds14. Removed T data of subjects 63<U+2013>78. 77 subjects. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (32 missings in sequence TRTR and 31 in sequence RTRT). Missings / period: 8/1, 12/2, 18/3, 25/4. No outliers. A data frame with 245 observations on the following 6 variables:

  rds18

  subject	a factor with 77 levels: 1, 2, …, 78
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 19 Data set based on rds18. Removed data of subjects 63<U+2013>78. 61 subjects. Unbalanced (31 subjects in sequence TRTR and 30 in RTRT) and incomplete (14 missings in both sequences). Missings / period: 0/1, 4/2, 9/3, 15/4. Two outliers (subjects 18 and 51 in sequence RTRT). A data frame with 216 observations on the following 6 variables:

  rds19

  subject	a factor with 61 levels: 1, 2, …, 62
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 20 Data set based on rds19. Extreme outlier of R (subject 1) introduced: original value <U+00D7>100). 61 subjects. Unbalanced (31 subjects in sequence TRTR and 30 in RTRT) and incomplete (14 missings in both sequences). Missings / period: 0/1, 4/2, 9/3, 15/4. Two outliers (subjects 1 and 51 in sequence RTRT). A data frame with 216 observations on the following 6 variables:

  rds20

  subject	a factor with 61 levels: 1, 2, …, 62
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 21 Based on ds01. 77 subjects. One extreme result of subjects 45 & 52 set to NA. Unbalanced (39 subjects in sequence TRTR and 38 in RTRT) and incomplete (seven missings in sequence TRTR and five in sequence RTRT). Missings / period: 1/1, 1/2, 8/3, 2/4. No outliers. A data frame with 298 observations (2 NA) on the following 6 variables:

  rds21

  subject	a factor with 61 levels: 1, 2, …, 62
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 25 Simulated with heteroscedasticity ( = 50%, = 80%), = = 130%, GMR = 0.85. 70 subjects. Balanced (70 subjects in both sequences) and complete. No outliers. A data frame with 280 observations on the following 5 variables:

  rds25

  subject	a factor with 70 levels: 1, 2, …, 70
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

• Reference dataset 26 54 subjects. Balanced (27 subjects in both sequences) and incomplete (two missings in both sequences). Missings / period: 0/1, 0/2, 2/3, 2/4. One outlier (subject 49) in sequence RTRT. A data frame with 216 observations on the following 5 variables:

  rds26

  subject	a factor with 54 levels: 1, 2, …, 57
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

  In the source evaluated by SAS for ABEL. Reported results (Method A):

  SAS Proc GLM

  CVwR	60.25%
  PE	151.3%

• Reference dataset 29 Simulated with heteroscedasticity (), GMR = 0.90. 12 subjects. Imbalanced (five subjects in sequence TRTR and seven in sequence RTRT) and incomplete (three missings in sequence TRTR and four in sequence RTRT). Missings / period: 0/1, 1/2, 2/3, 4/4. One outlier (subject 11) in sequence RTRT. A data frame with 41 observations on the following 5 variables:

  rds29

  subject	a factor with 12 levels: 1, 2, …, 20
  period	a factor with 4 levels: 1, 2, 3, 4
  sequence	a factor with 2 levels: TRTR, RTRT
  treatment	a factor with 2 levels: T, R

Details

Dataset	N	(%)	Evaluation
rds01	77	>30	method.A(), method.B()
rds06	77	>30	method.A(), method.B()
rds08	222	>30	method.A(), method.B()
rds09	222	>30	method.A(), method.B()
rds12	77	>30	method.A(), method.B()
rds13	222	>30	method.A(), method.B()
rds14	77	>30	method.A(), method.B()
rds15	222	>30	method.A(), method.B()
rds18	77	>30	method.A(), method.B()
rds19	61	>30	method.A(), method.B()
rds20	61	>30	method.A(), method.B()
rds21	77	>30	method.A(), method.B()
rds25	70	>30	method.A(), method.B()
rds26	54	>30	method.A(), method.B()

References

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

Patterson SD, Jones B. Bioequivalence and Statistics in Clinical Pharmacology. Boca Raton: CRC Press; 2 edition 2016. p105--6.

Examples

# NOT RUN {
str(rds01)
summary(rds01[2:6])
# }