Bioequivalence and Bioavailability Forum

Questions and Ambiguities [BE/BA News]

posted by d_labes  – Berlin, Germany, 2011-03-28 16:16 (4938 d 06:18 ago) – Posting: # 6822
Views: 35,503

Dear Helmut,

❝ Period ratios (second / first administration):

❝ Type 3: SAS according to R-doc - 2 outliers (#46: 3.524, #45: 26.08)

❝ Type 5: or is this SAS? - 2 outliers

❝ Type 6: Minitab, SPSS, Phoenix/WinNonlin - 2 outliers

❝ ...

SAS has 5 different percentile definitions. The default is:
Let n*p=j+g where j is the integer part, g is the fractional part, n is the number of values, x the ordered values.
Let y denote the percentile. Then (SAS PCTLDEF=5)
  y = 0.5*(xj+xj+1) if g=0
  y = xj           if g>0
This corresponds to R's Type 2 I think.

❝ Don’t know what to do. Suggestions?

If the 'outlier' considerations based on the crippled EMA model makes any sense at all, which I'm not convinced at all , I would vote for an analysis of the residuals, not the period ratios also they appeared a natural choice on the first view.
Pro's:

• Period effects accounted for
  
• Analysis within the log domain (deemed necessary for AUC, Cmax)
  
• Distribution hopefully nearly normal, nearly symmetric because of the previous point, such that the 3xIQR rule can be applied reasonably
  
• Independent of order (first/second or second/first)

Con's:

• Period effects different from the whole model, because of throwing away all data under Test, residuals therefore may be biased
  
• Residuals not independent because of the model fitted (2 values of residual on a subject only different in sign, must throw away 1/2 of them)

But these Con's are unavoidable because of the EMA 'model', whatever here is modelled.
To add more ambiguities:

• simple residuals?
• studentized residuals?
• external studentized residuals (leave-one-out residuals)?
  
• other influence statistics (e.g. Cook's distance)?

Complete thread:

• EMA BE-GL: Clarifications / Corrections? Helmut 2010-06-22 18:53 [BE/BA News] 
  • Good news!? d_labes 2010-06-23 10:09
    • Good news!? Helmut 2010-06-23 10:11
      • Update Helmut 2011-02-05 18:48
        • Q&A published 14 March 2011 Helmut 2011-03-16 13:44
          • Q&A published 14 March 2011 ElMaestro 2011-03-16 14:20
          • Phoenix/WinNonlin 6.1.0.173 Helmut 2011-03-17 04:23
          • ANOVA party prevails d_labes 2011-03-17 11:00
            • THX! Helmut 2011-03-19 02:59
              • Outlier d_labes 2011-03-24 11:55
                • Outliers - yes, but how? Helmut 2011-03-24 15:09
                  • Questions and Ambiguitiesd_labes 2011-03-28 14:16
                  • Residuals and Outliers in Replicate Design Crossover Studies d_labes 2011-04-04 08:53
              • Info requested ElMag 2011-03-24 12:45
                • Confused as well... Helmut 2011-03-24 16:50
          • Q&A published 14 March 2011 Priyanka_S 2011-03-21 14:28
            • SAS code: Warning d_labes 2011-03-21 16:08
              • Copy & paste Helmut 2011-03-21 22:38
                • Subtleties, flaws, questions d_labes 2011-03-22 09:24
                  • Subtleties, flaws, questions Helmut 2011-03-27 20:35
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                      • Not estimable in the model ElMaestro 2017-03-14 11:02
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                          • Not estimable in the model ElMaestro 2017-03-14 12:41
                      • Not estimable in the model Helmut 2017-03-18 21:59
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