Bioequivalence and Bioavailability Forum

Hi Uday,

Please let me know more details. I can help you with outliers treatment.

Best,
SKM

Hi UdayK,

❝ […] outlier test using Phoenix WinNonlin Software (Studentized residual method) and R-Software (code) in the Bioequivalence 2way cross design.

“Studentized residual” is an ambiguous term. There are two flavors:

1. Internally studentized (aka “standardized”), where
   \(\widehat{\sigma}^2={1 \over n-m}\sum_{j=1}^n \widehat{\varepsilon\,}_j^{\,2}\)
   
2. Externally studentized, where
   \(\widehat{\sigma}_{(i)}^2={1 \over n-m-1}\sum_{\begin{smallmatrix}j = 1\\j \ne i\end{smallmatrix}}^n \widehat{\varepsilon\,}_j^{\,2}\)
   

#1 is easily accessible in Phoenix WinNonlin (divide the raw residual by the standard error). Assess only the first period. The value of the other period has the same value but with the opposite sign and is therefore, not informative. No idea how to get #2 In WinNonlin. Ask at Certara’s forum.
Both are easily obtained in SAS, R,…

In R for the fixed effects model (untested!):

mod  <- lm(log(PK) ~ sequence + subject%in%sequence + period + treatment,
                     data = yourdata)
res1 <- rstandard(mod) # 1. Internally studentized (standardized)
res2 <- rstudent(mod)  # 2. Externally studentized

Note that #2 is in general more restrictive than #1, i.e., it might be that you detect more outliers.
BTW, which outlier test are you thinking of? See also there and this thread at stackoverflow.

Hi Uday,

Try Lund test in R package. If you want, I can help you out.

Cheers,
SKM

Hi udayk,

You may consider bear - an R package if you like. With bear, you can do outlier detection analysis (ODA) for a 2x2x2 BE study. Bear provides the following ODAs:

1. Test for Normality (Pearson): studentized intra-subject residuals & studentized inter-subject residuals;
   
2. Hotelling T² with Chi-square Test;
   
3. Test for Equality of Intra-subject Variabilities between Formulations; and
   
4. Cook's distance.

For more info, please see my signature panel.