Bioequivalence and Bioavailability Forum

Dear all,

We like to announce and share the new release of bear v2.2.0. The most important new function in this release is the data analysis for replicate crossover BE study (such as 2-tr x 2-seq x 3 periods, 2x2x4... up to 2x2x6) using lme (same as SAS PROC MIXED) from R package nlme. Now we are working on parallel BE study (2x2x1). Please use "Packages" -> "Update packages" from R console to install the new version if you have installed previous version. You can browse this page for how-to-install R packages. Other new functions added in bear v2.2.0 are listed as follows:

• add point estimate along with 90% CI in output file called Statistical_summaries.txt (suggested by DLabes).
  
• add sample size estimation for replicate BE study, and output re-arrangement.
  
• add Hotelling T² test and boxplots for outlier detection
  
• add Quantiles for intrasubject and intersubject (with boxplot)
  
• add replicated study for 2*2*3, 2*2*4, 2*2*5, and 2*2*6 (using lme to analyze replicated BE study)
  
• add sample size estimation for replicated study (using 2*2*2 sample size estimation extended to 2*2*n sample size of replicate crossover design)

The following are some output examples obtained from bear v2.2.0.

<<Sample Size Estimation>>

Upper acceptance limit = 125(%)
Lower acceptance limit = 80(%)
    Expected ratio T/R = 95.00(%)
          Target power = 80.00(%)
      Intra-subject CV = 20.0(%)

study       2x2x2     2x2x3        2x2x4
design    crossover replicated   replicated
------- ----------- ------------ ----------
  N          20        16           10

Estimated power= 83.46802(%)

Hotelling T² test
(...)  Hotelling T^2   
--------------------------------------------------------------------------
   subj  HT_Cmax HT_lnCmax HT_AUC0t HT_lnAUC0t HT_AUC0INF HT_lnAUC0INF
1     1  0.88638   0.85650  0.97444    0.90466    0.82225      0.76937
2     2  1.37871   1.25816  0.46862    0.48286    0.54162      0.56592
3     3 10.76389   8.19027  2.55956    2.47460    2.15554      2.13130
4     4  0.59829   0.53345  1.36768    1.19256    1.32453      1.15615
5     5  1.82827   1.97183  1.27839    1.29252    1.17989      1.20035
6     6  1.59714   1.41680  1.45271    1.28884    1.27021      1.13141
7     7  0.01658   0.04381  0.71059    0.65357    0.68229      0.63622
8     8  4.67137   3.47390  0.06496    0.13465    0.00974      0.04163
9     9  0.58431   0.55860  0.90283    0.87754    0.91402      0.88872
10   10  0.99704   0.92403  1.53365    1.57887    1.21948      1.24508
11   11  5.41157   7.05871  5.44089    6.42777    5.76052      6.93837
12   12  5.58454   7.54222  4.16338    4.89954    4.29064      5.12118
13   13  2.26730   2.47522  4.16519    4.53151    3.94232      4.17831
14   14  0.24448   0.31984 11.39161    9.03305   15.08591     11.63398

-------------------------------------------------
HT_Cmax: Hotelling T^2 for Cmax
HT_lnCmax: Hotelling T^2 for lnCmax
HT_AUC0t: Hotelling T^2 for AUC0t
HT_lnAUC0t: Hotelling T^2 for lnAUC0t
HT_AUC0INF: Hotelling T^2 for AUC0INF
HT_lnAUC0INF: Hotelling T^2 for lnAUC0INF(...)

Display the point estimate:
(...)  BE Summary Report  - replicate BE study                         
--------------------------------------------------------------------------
  Dependent Variable: lnCmax                                               
--------------------------------------------------------------------------
          n1(seq 1)= 7
          n2(seq 2)= 7
          N(n1+n2) = 14
          MEAN-ref = 7.363255
         MEAN-test = 7.409809
Estimate(test-ref) = 0.04655381

**************** Classical (Shortest) 90% C.I. for lnCmax *****************
  CI90_lower Point_estimated CI90_upper
1    100.312         104.765    109.416
--------------------------------------------------------------------------

And finally, two boxplots.



Hope bear can be useful for you.

All the best,
Hsin-ya Lee, Yung-jin Lee
College of Pharmacy,
Kaohsiung Medical University,
Kaohsiung, Taiwan