Extra-reference or partial replicate design [Software]

posted by d_labes  – Berlin, Germany, 2008-12-12 11:51 (5900 d 01:50 ago) – Posting: # 2912
Views: 31,009

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 sWT.
Black magic :confused: 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

Regards,

Detlew

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