test2x2: Bioequivalence test for a variable of a 2x2 study
In BE: Bioequivalence Study Data Analysis

Description Usage Arguments Details Value Author(s) Examples

It performs conventional bioequivalence test for 2x2 study. Basic assumption is that the variable is distributed as a log-normal distribution. This is SAS PROC GLM style. If you want PROC MIXED style use nlme::lme.

1	test2x2(bedata, Var)

bedata

Data table name. This should have at least the following columns and a variable column to be tested. Var column values should be all positive values.

  
 GRP : Group or Sequence, 'RT' or 'TR'
 PRD : Period, 1 or 2
 SUBJ : Subject ID
 TRT : Treatment or Drug, 'R' or 'T'

Var

Variable to be tested. This should be one of the column names in bedata table. Usually 'AUClast' or 'Cmax'

It tests Var variable equivalency from a 2x2 study. Current regulatory requirement is that the 90% confidence interval of geometric mean ratio (Test/Reference) should be within [0.8, 1.25].

`Analysis of Variance (log scale)`	Analysis of Variance in log scale
`Between and Within Subject Variability`	Variance in log scale and coefficient of variance in original scale
`Least Square Means`	Geometric means
`90% Confidence Interval`	90% confidence interval of geometric mean ratio (T/R)
`Sample Size`	Sample size for the replication of this study

Kyun-Seop Bae k@acr.kr

1 2	test2x2(NCAResult4BE, "AUClast") test2x2(NCAResult4BE, "Cmax")

Loading required package: rtf
$`Analysis of Variance (log scale)`
               Df Sum Sq  Mean Sq F value    Pr(>F)    
SUBJECT        32 2.8755 0.089859  3.1839 0.0008743 ***
GROUP           1 0.1025 0.102461  1.1454 0.2927732    
SUBJECT(GROUP) 31 2.7730 0.089453  3.1695 0.0009544 ***
PERIOD          1 0.0000 0.000030  0.0011 0.9740824    
DRUG            1 0.0364 0.036435  1.2910 0.2645764    
ERROR          31 0.8749 0.028223                      
TOTAL          65 3.7868                               
---
Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1

$`Between and Within Subject Variability`
                                Between Subject Within Subject
Variance Estimate                    0.03061507     0.02822265
Coefficient of Variation, CV(%)     17.63193968    16.91883011

$`Least Square Means (geometric mean)`
                Reference Drug Test Drug
Geometric Means       5092.098  4858.245

$`90% Confidence Interval of Geometric Mean Ratio (T/R)`
                 Lower Limit Point Estimate Upper Limit
90% CI for Ratio    0.889436      0.9540753    1.023412

$`Sample Size`
                      True Ratio=1 True Ratio=Point Estimate
80% Power Sample Size            6                         7

$`Analysis of Variance (log scale)`
               Df Sum Sq  Mean Sq F value  Pr(>F)  
SUBJECT        32 2.8615 0.089422  2.2376 0.01367 *
GROUP           1 0.0001 0.000097  0.0011 0.97430  
SUBJECT(GROUP) 31 2.8614 0.092303  2.3097 0.01132 *
PERIOD          1 0.0047 0.004717  0.1180 0.73348  
DRUG            1 0.0068 0.006838  0.1711 0.68198  
ERROR          31 1.2389 0.039963                  
TOTAL          65 4.1123                           
---
Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1

$`Between and Within Subject Variability`
                                Between Subject Within Subject
Variance Estimate                    0.02616997      0.0399631
Coefficient of Variation, CV(%)     16.28355371     20.1921690

$`Least Square Means (geometric mean)`
                Reference Drug Test Drug
Geometric Means       825.5206  808.8778

$`90% Confidence Interval of Geometric Mean Ratio (T/R)`
                 Lower Limit Point Estimate Upper Limit
90% CI for Ratio   0.9013625      0.9798396    1.065149

$`Sample Size`
                      True Ratio=1 True Ratio=Point Estimate
80% Power Sample Size            8                         8