Datasets from the public domain, edited, or obtained by simulations to be evaluated by method.A()
and/or method.B()
.
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:
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 ) |
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:
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:
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:
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:
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:
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:
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
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:
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:
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:
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:
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:
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:
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 |
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:
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 |
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() |
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.
# NOT RUN {
str(rds01)
summary(rds01[2:6])
# }
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