3 replies to this topic

[Helmut Schütz]

Dear all,
 
see the subject line…
I want to update the reference-scaling templates for the EMA’s methods. Recently the WHO started a pilot phase exploring reference-scaling for AUC. The WHO requires a 4-period full replicate design (TRTR|RTRT) in order to compare s_wT with s_wR. Easy to set up the fixed effects model Sequence+Subject(Sequence)+Period as given in the EMA’s Q&A document. As usual with the EMA, superfluous terms. The simple Subject+Period gives an identical residual variance. But we want to make regulators happy, right?

• Include subjects with two administrations of R, calculate s_wR as sqrt(Residual Variance) and
  CV_wR as sqrt(exp(Residual Variance)–1).
  Required for the WHO and widening of the BE-limits if CV_wR >30% according to [L,U] = exp(∓0.76s_wR).
• Include subjects with two administrations of T, calculate s_wT as sqrt(Residual Variance)
  Required for the WHO.

Works as a charm if the design is one of the currently implemented full replicates – and a couple of new ones as well. But the template should be able to handle all replicate designs (i.e., also the partial replicate TRR|RTR|RRT and the extra-reference TRR|RTR). For these designs I got the ERROR 11068 for #2. As expected, since T is not repeated and the remainder of the template is not executed. Any ideas to bypass #2?

[mittyright]

Dear Helmut,

 

yes, you cannot do that directly,

I made some trick, hope it will make sense to you.

Works fine with my general template attached

The project is made in PHX7.

 

 

Hope it helps,

Mittyright

 

Attached Files

•  EMA ABEL Project Template v1_4_3_4_executed.phxproj   5.9MB   414 downloads

[Helmut Schütz]

Hi mittyright,

 

you made my day!

 

I made some trick, hope it will make sense to you.

 

I does. I also had the idea to introduce a dummy variable but didn’t know how.

 

THX a lot!

[dlweiner]

Dear Helmut,

 

I am working on a study where the original design was for two sequences, ABAB/BABA but due to dosing errors at the site, two different sequences were also applied to some subjects.  They were AAAB and BBAA (A is the test and B the reference). So there are 4 sequences in total.  Do you have a modifed version of the PHX RSABE template that can handle this design?

 

Thanks,

Dan Weiner