Bioequivalence and Bioavailability Forum

dear all,

We have built the outliers detection function with bear for BE study. As we released bear, this function (intra-subject residuals) has been suggested by some experts of this Forum. Here are some outputs generated from bear as preview before we officially release it within next few days. Before that, we will need your comments about this. Many thanks.
...

               Intra-subject and inter-subject residuals                 
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   subj   Obs   Exp  Intra Stud_Intra  Inter Stud_Inter
8     1 7.398 7.491 -0.093     -1.126  0.138      0.724
1     2 7.300 7.409 -0.109     -1.318  0.098      0.516
9     3 7.637 7.622  0.015      0.179  0.400      2.095
2     4 7.225 7.312 -0.086     -1.044 -0.097     -0.506
10    5 7.233 7.353 -0.119     -1.447 -0.138     -0.725
3     6 7.471 7.400  0.071      0.855  0.081      0.422
11    7 7.404 7.442 -0.037     -0.454  0.040      0.207
4     8 7.570 7.480  0.090      1.096  0.239      1.252
12    9 7.473 7.446  0.027      0.322  0.048      0.251
5    10 7.236 7.270 -0.034     -0.413 -0.180     -0.945
13   11 7.428 7.289  0.139      1.682 -0.266     -1.393
6    12 7.341 7.236  0.105      1.275 -0.249     -1.302
14   13 7.381 7.311  0.070      0.843 -0.221     -1.159
7    14 7.377 7.414 -0.037     -0.451  0.108      0.563
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Obs: Observed lnCmax
Exp: Expected lnCmax
Intra: Intra-subject residuals
Stud_Intra: Studentized intra-subject residuals
Inter: Inter-subject residuals
Stud_Inter: Studentized inter-subject residuals
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...
         Test results for normality assumption  (Shapiro-Wilk)             
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             Parameter    Test P_value
1    lnCmax_Stud_Intra 0.93758  0.3882
2    lnCmax_Stud_Inter 0.94438  0.4773
3   lnAUC0t_Stud_Intra 0.87462  0.0488
4   lnAUC0t_Stud_Inter 0.90178  0.1197
5 lnAUC0INF_Stud_Intra 0.86833  0.0398
6 lnAUC0INF_Stud_Inter 0.91282  0.1731

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Stud_Intra: studentized intra-subject residuals
Stud_Inter: studentized intra-subject residuals
Shapiro-Wilk: the normality of the studentized intra-subject residuals and
              the studentized inter-residuals was examined using the test 
              of Shapiro-Wilk.                                             
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             Test results for normality assumption  (Pearson)             
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  Parameter     Test P_value
1    lnCmax -0.19043  0.5143
2   lnAUC0t -0.39188  0.1658
3 lnAUC0INF -0.39646  0.1605

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Pearson: Pearson's correlation coefficient
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             Test results for normality assumption  (Spearman)             
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  Parameter     Test P_value
1    lnCmax -0.28352  0.3253
2   lnAUC0t -0.23956  0.4086
3 lnAUC0INF -0.26154  0.3656

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Spearman: Spearman's rank correlation coefficient
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               Test results for equality of variabilities                 
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                   Method     Test P_value
1          lnCmax_Pearson -0.18320  0.5307
2    lnCmax_Pitman_Morgan  0.41674  0.5307
3         lnCmax_Spearman -0.20879  0.4731
4         lnAUC0t_Pearson -0.11204  0.7029
5   lnAUC0t_Pitman_Morgan  0.00011  0.9917
6        lnAUC0t_Spearman -0.16044  0.5838
7        lnAUC0INFPearson -0.09948  0.7351
8 lnAUC0INF_Pitman_Morgan  0.00061  0.9806
9      lnAUC0INF_Spearman -0.15604  0.5944



   Point and interval estimation of inter- and intra-subject variability 
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              Parameter Point_Estimate CI95_lower CI95_upper
1          lnCmax_intra          0.016      0.008      0.043
2          lnCmax_inter          0.003     -0.008      0.022
3     lnCmax_intraclass          0.144     -0.421      0.628
4           lnCmax_prob        0.31164          -          -
5         lnAUC0t_intra          0.032      0.017      0.088
6         lnAUC0t_inter         -0.008     -0.023      0.009
7    lnAUC0t_intraclass         -0.316     -0.726      0.261
8          lnAUC0t_prob        0.86423          -          -
9       lnAUC0INF_intra          0.031      0.016      0.084
10      lnAUC0INF_inter         -0.007     -0.022      0.010
11 lnAUC0INF_intraclass         -0.303     -0.719      0.274
12       lnAUC0INF_prob        0.85363          -          -

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intra: intra-subject variability
inter: inter-subject variability
intraclass: intraclass correlation
prob: the probability for obtaining a negative estimate of inter-subject
      variability
CI95: 95% confidence interval
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We only show the part of Cmax here. The AUC0-t and AUC0-inf will also display when running bear. This will be included in the output file of 'ANOVA_stat.txt'. also we have some normal Q-Q plots for outliers detection purposes.


We built these functions for bear mostly based on the textbook of Chow SH, Liu, JP. "Design and Analysis of Bioavailability and Bioequivalence Studies", Third Edition (Chapman & Hall/Crc Biostatistics Series).

All the best,
Hsin-ya Lee & Yung-jin Lee
College of Pharmacy,
Kaohsiung Medical University,
Kaohsiung, Taiwan 807
http://pkpd.kmu.edu.tw/bear