Reason to go for Partial and Full Replicate [Design Issues]
Hello kms.srinivas,
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.
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.
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.
❝ 1. In which circumstances, Partial or Full Replicate design should be used?
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?
❝ 3. Which is better design? Full or Partial replicate? Why?
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?
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.
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Pass or fail!
ElMaestro
Pass or fail!
ElMaestro
Complete thread:
- Reasons to go for Partial and Full Replicate kms.srinivas 2018-03-09 05:38 [Design Issues]
- Reason to go for Partial and Full ReplicateElMaestro 2018-03-09 10:17
- Reasons to go for Full Replicate Helmut 2018-03-09 13:17