Bioequivalence and Bioavailability Forum

scorp2011
☆

India,
2015-06-15 14:36
(3560 d 23:03 ago)

Posting: # 14957
Views: 8,191

SAS code for 3-period, partial-replicated crossover study [RSABE / ABEL]

We have two Test formulations (T1 and T2) and One single Reference formulation (R). We want to test for bioequivalence of each test formulation against the reference formulation i.e. T1 vs. R and T2 vs. R. The test drug is a candidate of "NTI" Please suggest me the whether we can analyze the study as per the SAS code (after adequately modifying the same) provided by the USFDA in Warfarin OGD guidance.
Regards
Sonu

d_labes ★★★ Berlin, Germany, 2015-06-15 15:24 (3560 d 22:15 ago) @ scorp2011 Posting: # 14958 Views: 7,049	SAS code for 3-period, partial-replicated crossover study Post reply
	Dear Sonu, as far as I could see your study design is not a partial replicate design. There is no replication (i.e. more than one application of the reference within each subject) if you use three periods and will apply each treatment on each subject. If I'm correct in describing your design you can not apply scaled ABE for NTID's. Or do I miss some thing? — Regards, Detlew

MGR ★ India, 2015-06-15 15:34 (3560 d 22:05 ago) @ d_labes Posting: # 14959 Views: 7,234	SAS code for 3-period, partial-replicated crossover study Post reply
	Hi All, One of my sponsor asked to do a Partial replicate study, in which there are two tests and one reference. What will be the possible sequences used in the study? Thanks in advance. — Regards, MGR

ElMaestro
★★★

Denmark,
2015-06-15 15:46
(3560 d 21:53 ago)

@ MGR
Posting: # 14960
Views: 6,990

SAS code for 3-period, partial-replicated crossover study

Post reply

Hi MGR,

❝ One of my sponsor asked to do a Partial replicate study, in which there are two tests and one reference. What will be the possible sequences used in the study?

It would be permutations of T₁T₂RR.
It does not sound right to me, intuition and such, but it is definitely possible. 4 periods.

If you insist on 3 periods, I wonder if you could do Perm(RRT₁) and Perm(RRT₂). Three periods, 6 sequences.... rubbish? Some subjects would not be exposed to both Tests I guess. Naw, this sounds too weird too for my taste buds.

—
Pass or fail!
ElMaestro

d_labes
★★★

Berlin, Germany,
2015-06-15 16:50
(3560 d 20:48 ago)

@ ElMaestro
Posting: # 14961
Views: 6,969

Partial-replicated crossover study with 2 Tests

Post reply

Dear ElMaestro, dear MGR!

Both of your described designs are of course possible ones.
But both are not usable if you think in terms of scaled ABE for NTID's as described in the Warfarine guidance. The algo described there relies on a full replicate design because you have to evaluate the (1 - α)100% CI for σwT/σwR, the ratio of sd's of intra-subject variabilities of Test and Reference.

For "normal" scaled ABE aimed to a FDA submission there are some (IMHO) unresolved issues. Just to name some:

How to estimate the sample size for scaled ABE for these designs?
How exactly to adapt the algorithm described in the FDA Progesterone guidance to both suggested designs?
Pairwise evaluation like the EMA suggestion for 3×3 or 4×4 cross-over designs doesn't really help since for the RR evaluation all data have to be used if such designs should have any advantage over 2 separate studies.

I personally wouldn't go with any design without knowledge about how to plan and how to evaluate!

—
Regards,

Detlew

SAS code for 3-period, partial-replicated crossover study [RSABE / ABEL]

SAS code for 3-period, partial-replicated crossover study

SAS code for 3-period, partial-replicated crossover study

SAS code for 3-period, partial-replicated cross­over study

Partial-replicated crossover study with 2 Tests

SAS code for 3-period, partial-replicated crossover study