Michael (aka “mittyri” here and “mittyright” at Certara’s forum) and I updated the Phoenix WinNonlin template for the EMA’s ABEL ( free download
- Works in Phoenix 6.4 and 7.0 (previously there were two versions of the template in order to deal with the different graphics engines).
- 4-period 2-sequence design
- TTRR | RRTT
Useful for steady state studies.4-period 4-sequence designs
Both are not recommended (confounded effects) and included only for completeness.
- TRTR | RTRT | TRRT | RTTR
- TRTR | RTRT | TTRR | RRTT
3-period 2-sequence (partial) replicate design
Not recommended since lacking period effects have to be assumed. Since the test is not administered in the third period, the treatment comparison will be biased in the presence of true period effects. This design should be avoided and is included only for completeness.
- TRR | RTR (aka “extra reference design”)
Plots of standardized residual vs. subject and vs. model predictions.
Comparison of within-subject variabilities of test and reference (full replicate designs only).
- Based on swT∕swR-ratio (like in PBE and IBE).
- Based on the upper confidence limit of the σwT∕σwR-ratio (like in the FDA’s warfarin guidance).
- Q&A-document of the EGA/EMA joint workshop.
- The name of both treatments can be specified (previously only the one of the reference).
Experimental (not officially supported)
- TR | RT | TT | RR (aka Balaam’s design)*
Not recommended due to its very poor power characteristics and included only for completeness. Cross-validated only against R v3.4.1 with one data set.
The template was developed in PHX 126.96.36.1998 and tested in PHX 188.8.131.525. The template was cross-validated with 26 data sets (all designs, up to 360 subjects) against SAS v9.4 (Methods A, B, C), R v3.4.1 (A, B), STATISTICA (A, B), and partly
(Q&A data sets I and II; Methods A, B) against STa
v14, SPSS v22, and JMP v10. As usual, use at your own risk.
In your project delete all PDFs in the
folder in order to reduce its size. The run-time is slightly better than in previous versions but needs patience. Since Phoenix swaps intermediate results to the system drive, it will take a while to complete. On my machine (with fast solid-state drives) execution of the Q&A’s data set I takes 2:15 minutes (Phoenix 6.4) and 1:50 minutes (Phoenix 7.0). If you have a hard drive, it may take substantially (?) longer.
Reports of defects and especially experiences with Windows installed on a hard drive are welcome at the
- Balaam LN. A Two-Period Design with t2 Experimental Units. Biometrics 1968;24(1):61–73. doi:10.2307/2528460.