Helmut
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Vienna, Austria,
2017-08-23 21:45
(2409 d 11:01 ago)

Posting: # 17746
Views: 6,041
 

 Phoenix Template v1.5 for the EMA’s ABEL [Software]

Dear all,

Michael (aka “mittyri” here and “mittyright” at Certara’s forum) and I updated the Phoenix WinNonlin template for the EMA’s ABEL ([image] free download).
    New
  • 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
    • TRTR | RTRT | TRRT | RTTR
    • TRTR | RTRT | TTRR | RRTT
  • 3-period 2-sequence (partial) replicate design
    • TRR | RTR (aka “extra reference 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.
  • 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).
  • Documents folder
    • Q&A-document of the EGA/EMA joint workshop.
    • Instructions.
    Changed
  • 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)1
    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 6.4.0.768 and tested in PHX 7.0.0.2535. 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 STaTa v14, SPSS v22, and JMP v10.2 As usual, use at your own risk.

In your project delete all PDFs in the Documents 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
Certara Forum (registration necessary).


  1. Balaam LN. A Two-Period Design with t2 Experimental Units. Biometrics 1968; 24(1): 61–73. doi:10.2307/2528460.
  2. Schütz H, Labes D, Tomashevskiy M, González de la Parra M, Shitova A, Fuglsang A. Reference Datasets for Studies in a Replicate Design Intended for Average Bioequivalence with Expanding Limits. AAPS J. 2020; 22: 44. doi:10.1208/s12248-020-0427-6.

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Helmut Schütz
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sameep
☆    

India,
2021-08-13 15:26
(958 d 17:21 ago)

@ Helmut
Posting: # 22519
Views: 1,990
 

 Phoenix Template v1.5 for the EMA’s ABEL

Greetings!

❝ 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).


Is an updated version of the Template, compatible with Phoenix 8.3 available?
Requesting to share the same.

Regards,
Sameep.
SDavis
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Homepage
UK,
2021-08-19 19:44
(952 d 13:02 ago)

@ sameep
Posting: # 22529
Views: 1,876
 

 Phoenix Template v1.5 for the EMA’s ABEL

Hi Sameep, generally I would expect a Phoenix 7 project to run in 8.x, if you are gettign some errors then please email support and we will look into it.

Simon.

Simon
Senior Scientific Trainer, Certara™
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https://www.certarauniversity.com/dashboard
https://support.certara.com/forums/
Achievwin
★    

US,
2021-08-24 17:30
(947 d 15:16 ago)

@ Helmut
Posting: # 22544
Views: 1,795
 

 FDA’s RSABE

Hi Helmut:

Can you also please share RSABE example for US FDA.

Regards,


Edit: Subject line changed; see also this post #2. [Helmut]
Helmut
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Homepage
Vienna, Austria,
2021-08-24 17:54
(947 d 14:52 ago)

@ Achievwin
Posting: # 22547
Views: 1,807
 

 RSABE: Examples

Hi Achievwin,

❝ Can you also please share RSABE example for US FDA.


Regrettably the FDA didn’t publish reference data sets…

Four data sets (calculations in full precision, results with five significant digits):$$\small{\begin{array}{ccccccccc}
\hline
\mathsf{Ref.} & \mathsf{Design} & s_\text{wR} & \geq0.294 & \mathsf{critbound} & \leq0 & PE & \in \left\{ 0.8000-1.2500 \right\} & \mathsf{aggregate / mixed}\\
\hline
1 & \text{TRRT|RTTR} & 0.38604 & \text{yes} & +0.076541 & \text{no} & 0.73339 & \text{no} & \text{fails RSABE}\\
2 & \text{TRRT|RTTR} & 0.39453 & \text{yes} & -0.087152 & \text{yes} & 1.0360\;\; & \text{yes} & \text{passes RSABE}\\
3 & \text{TRTR|TRTR} & 0.44645 & \text{yes} & -0.092076 & \text{yes} & 1.1546\;\; & \text{yes} & \text{passes RSABE}\\
4 & \text{TRTR|TRTR} & 0.34358 & \text{yes} & -0.051725 & \text{yes} & 1.1102\;\; & \text{yes} & \text{passes RSABE}\\\hline
\end{array}}$$ Enjoy, if you can.


  1. U.S. Food and Drug Administration, CDER. Bioequivalence Studies. Bioequivalence study files. Rock­ville. 1997. [image] webarchive 2017 (Cmax data of Drug 14a).
  2. Hauschke D, Steinijans VW, Pigeot I. Bioequivalence studies in drug development. Chichester: John Wiley; 2007. p. 216 (Cmax data).
  3. European Medicines Agency. EMA/582648/2016. Annex II. 21 September 2016.
  4. Patterson SD, Jones B. Bioequivalence and statistics in clinical pharmacology. Boca Raton: CRC Press; 2nd edition 2016. p. 105–6 (AUC data).

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
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