MGR
★    

India,
2015-06-24 12:52
(3669 d 10:18 ago)

Posting: # 14972
Views: 5,027
 

 Partial replicate for Canada [Design Issues]

Dear All,

Can we do a partial replicate study for Canada submission :confused:? If so what will be the procedure we have to follow?

Thank You,

Regards,
MGR
Helmut
★★★
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Vienna, Austria,
2015-06-24 14:27
(3669 d 08:44 ago)

@ MGR
Posting: # 14973
Views: 4,224
 

 Be aware of FA0(2)

Hi MGR,

❝ Can we do a partial replicate study for Canada submission :confused:?


Why didn’t you search the Guidelines / Guidances first? HC’s Guidance Document: Conduct and Analysis of Comparative Bioavailability Studies states in Section 2.3.1:

Replicated cross-over designs may also be used, where the formulations are tested more than once in the same subjects.


❝ If so what will be the procedure we have to follow?


Section 2.7.4.2:

By definition the cross-over design is a mixed effects model with fixed and random effects. The basic two period cross-over can be analysed according to a simple fixed effects model and least squares means estimation. Identical results will be obtained from a mixed effects analysis such as Proc Mixed in SAS®. If the mixed model approach is used, parameter constraints should be defined in the protocol.


Currently HC does not accept reference-scaling (though the “Scientific Advisory Committee on Phar­ma­ceutical Sciences and Clinical Pharmacology“ recommended in the June 2014 meeting FDA’s approach with a minimum sample size of 40 for the partial replicate and 24 for the four-period full replicate). The mixed-effect model (as given for SAS f.i. in FDA’s guidance or EMA’s Q&A-document ‘Method C’) with the FA0(2) parameterization of the covariance structure might fail to converge in partial replicate designs due to the over-spe­ci­fied model (see these posts). Either use FA0(1) instead or opt for a fully replicated three-period design (RTR|TRT).
It is beyond me why the partial replicate is so “popular”. Why do you want to use it?


Edit: see also this thread.

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