Bioequivalence and Bioavailability Forum • Replicate Study Designs

balakotu
★

India,
2012-07-09 11:16
(5103 d 12:57 ago)

Posting: # 8908
Views: 4,889

Replicate Study Designs [Design Issues]

Dear all please Suggest me,

As all of you aware that

Full replicate design and partial replicate design are recommended to demonstrate bioequivalence for high variable drugs.

Please suggest me about the following:

The best design out of Full replicate / partial replicate.
Basis for selection of design for pivotal in case intra subject CV is above 30% – means what should be looked at in the pilot data for design selection – ratio, power or 90%CI observed
Advantages of Full replicate over partial replicate and vice versa.
Disadvantages of both designs.

Regards
Kotu

Edit: Category changed. [Helmut]

Helmut
★★★

Vienna, Austria,
2012-07-09 17:27
(5103 d 06:46 ago)

@ balakotu
Posting: # 8911
Views: 4,208

Replicate Study Designs

Post reply

Dear Kotu!

From a purely (!) statistical point of view a full replicate design is ‘better’ because you get not only insights on the reference’s intra-subject variability but also of the test’s.
Not clear what you mean here. The pilot study should be a replicate as well (we have no Two-Stage Method yet). You should plan for power of 80–90%. Most people plan for 90% (best case: everything as expected) and try the keep the worst-case power (CV, PE, number of drop-outs) not far below 80%. Note that ‘classical’ sample size estimation is not applicable (GMR-restriction, 50% cut-off for EMA). Unless your set up your own simulations, see Endrényi & Tóthfalusi (2011).^*
See #1. One more period in the full replicate increases the chance of drop-outs. Might require to improve the bioanalytics (less plasma per individual sample since total blood volume in the study is limited to ~500 mL).
See #3 and this presentation.

László Endrényi, László Tóthfalusi
Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs
J Pharm Pharmaceut Sci 15(1), 73–84 (2011)
online

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