MGR ★ India, 2015-06-24 12:52 (3227 d 08:23 ago) Posting: # 14972 Views: 4,147 |
|
Dear All, Can we do a partial replicate study for Canada submission ? If so what will be the procedure we have to follow? Thank You, — Regards, MGR |
Helmut ★★★ Vienna, Austria, 2015-06-24 14:27 (3227 d 06:49 ago) @ MGR Posting: # 14973 Views: 3,543 |
|
Hi MGR, ❝ Can we do a partial replicate study for Canada submission ? 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. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |