Bioequivalence and Bioavailability Forum

Extra-reference or partial replicate design [Software]

posted by d_labes  – Berlin, Germany, 2008-12-12 11:51 (5972 d 04:27 ago) – Posting: # 2912
Views: 31,678

Dear all,

FYI:
The 3-sequence-3-period replicate design with the sequences

TRR
RTR
RRT

mentioned in MGR's post above is handled in the framework of the so-called Method of moments in

^[1] R.J. McNally
Tests for Individual and Population Bioequivalence Using 3-Period Crossover Designs

and the 2-sequence variant using only the two first sequences in

^[2] S.-C. Chow, J. Shao and H. Wang
Individual bioequivalence testing under 2×3 designs
Statist. Med. 2002; 21:629–648

which can be found ^[1] here and ^[2] there.

These papers deal with individual BE but the parts relevant for average BE can easily extracted.

Interesting enough these papers state, that the intra-individual variance component for T(est) is not identifiable/estimable, due to the "partial" replicate nature of these designs (replicates only for R).
Thus one would expect some difficulties with the FDA SAS code, which has a covariance parameter for that in the model. But my little experimentation with it and some artificial data for an extra-reference design show that the code is able to deliver a value for that variance parameter s_WT.
Black magic or some sort of perpetuum mobile of information?

Because the intra-individual variance for the Reference is identifiable (regardless which method, REML or method of moments) one could go with Reference scaled ABE as described in
Haidar et al.
Evaluation of a scaling approach for the bioequivalence of highly variable drugs
AAPS J. 2008 Sep;10(3):450-4. Epub 2008 Aug 26

Complete thread:

• SAS code of partial replicate design pa1kumar.anna 2008-12-01 09:51 [Software] 
  • Etiquette Ohlbe 2008-12-01 10:45
  • SAS code for what? d_labes 2008-12-02 09:17
    • partial replicate = 3-period replicate Helmut 2008-12-03 15:42
      • partial replicate = 3-period replicate MGR 2008-12-04 11:19
      • 3-period replicate designs and SAS d_labes 2008-12-04 14:17
        • Extra-reference or partial replicate designd_labes 2008-12-12 10:51
          • Extra-reference or partial replicate design Helmut 2008-12-12 11:34
            • Simple minded d_labes 2008-12-12 13:28
              • Simple minded Helmut 2008-12-12 14:58
                • SAS and WinNonlin d_labes 2008-12-12 15:44
                  • SAS and WinNonlin Helmut 2008-12-12 16:33
                    • SAS and WinNonlin BEQool 2024-07-29 09:38
                      • Phoenix RSABE-template Helmut 2024-07-29 13:29
                        • Phoenix RSABE-template BEQool 2024-07-29 19:47
                          • CVw in Phoenix RSABE-template Helmut 2024-07-30 09:15
                            • CVw in Phoenix RSABE-template BEQool 2024-07-30 10:56
                              • CVw in Phoenix RSABE-template and Power­TOST CI2CV() Helmut 2024-07-30 11:23
                                • CVw in Phoenix RSABE-template and Power­TOST CI2CV() BEQool 2024-07-31 05:49
                                  • General ABE? mittyri 2024-07-31 18:25
                                    • General ABE? BEQool 2024-08-01 05:45
                • Switchability and Prescribability in WinNonlin MGR 2008-12-30 10:12
                  • PBE and IBE in WinNonlin Helmut 2008-12-30 16:04
                    • PBE and IBE in WinNonlin MGR 2008-12-31 07:52
                      • Switchability NPavan 2009-01-12 13:10