Reason to go for Partial and Full Replicate [Design Issues]

posted by ElMaestro  – Denmark, 2018-03-09 11:17 (2234 d 10:39 ago) – Posting: # 18507
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Hello kms.srinivas,

❝ 1. In which circumstances, Partial or Full Replicate design should be used?

"Should" is perhaps slightly wrong. Generally, regulators tend not to make the choice of going replicate or partial replicate for any applicants.
Partial or full replicates can be used all the time. They tend to be advantageous if (and in my opinion only if) the study in which they are used shows a CVintra(ref) of >30%. Here's an element of predicting, guessing, expecting variability. You can often get inspiration from published studies/PARs/FOI information etc.

❝ 2. Can we go for 2 way crossover, when ISCV > 30% also?

Yes. In a sense it might incur a penalty in terms of sample size (study cost), but that will mainly be a hindsight conclusion.

❝ 3. Which is better design? Full or Partial replicate? Why?

Which is better food: chicken or veg?
Full replicate gives you an opportunity to derive intra-CV for Test. But that quantitity isn't much used, generally. If we talk widening of acceptance range then that is made on basis of intra-CV for Ref.
Full replicate is tougher on volunteers, because there will be more periods. All other factors equal, you will often see higher drop out rates towards the late periods.
Partial replicate is fine. RTR/RRT/TRR is a very good design. Note here are proponents of RTR/TRT design types on this forum, albeit I believe there isn't an explicit solid regulatory support for that type. This may constitute a type of semi-replicate which will grow into maturity with time.
Fitting RTR/RRT/TRR for FDA may be tricky, since the stats model -if I get it right- in SAS's world doesn't work well. It has to do with the lack of an intra-subject variance component for Test.

❝ 4. What is SAS code for Full and Partial Replicates?

Can't help.
But the code will differ depending on the country in which the dossier is submitted.

A much more personal remark: If in doubt (if CV is expected to be just around 30%, for example) , go for a 222BE design.

Pass or fail!

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