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venu
Junior

Mumbai, India,
2006-10-30 11:02

Posting: # 335
Views: 13,321
 

 WinNonlin [Software]

Hi,

Is it compulsory to use WinNonlin software for generating pharmacokinetic and statistical analysis for pilot and pivotal studies? If not what are the other software alternatives? :-)

Is it also compulsory to validate the WinNonlin software? :-)

With Regards,
Venu
Helmut
Hero
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Homepage
Vienna, Austria,
2006-10-30 12:56

@ venu
Posting: # 339
Views: 12,879
 

 not only WinNonlin...

Dear Venu!

» Is it compulsory to use WinNonlin software for generating pharmacokinetic and statistical analysis for pilot and pivotal studies?

No! :-D
Actually there is no regulation forcing you to use any software at all…
You may also calculate your ANOVA by means of (some) sheets of paper, a pencil and a pocket calculator (although in order to avoid errors, you should repeat this procedure, or let two persons do the job).

» If not what are the other software alternatives?

Kinetica from ‘Thermo Electron’ (not only BA/BE, but also NCA, ‘classical’ PK and population PK).
Drawbacks (up to the current version 4.4.1):
  • Besides an acceptance range of 0.80-1.25 only 0.70–1.43 is supported… (what about 0.75–1.33, 0.90–1.11)?!
  • Only 90% confidence interval possible (what about Brazil and multiple testing)?
EquivTest/PK from ‘statistical solutions’:
Drawbacks:
  • Only 2×2 designs are covered.
  • Acceptance ranges only 0.80-1.25 and 0.70-1.43!
Drawbacks of WinNonlin and Kinetica: both pieces of software are lacking the nonparametric method (which you need in many regulations for tmax); therefore you will need EquivTest anyhow. ;-)

An alternative for nonparametrics is StatXact from ‘Cytel’, which also comes as a plugin (StatXact PROCs) for SAS.

If you have a large budget – and the additional salary for a SAS-programmer - you also may use SAS for the entire evaluation…

If you know a statistician with some programming skills, you may adapt routines in any general-purpose statistical package (e.g., Stata, NCSS, Statistica, SPSS, Minitab, Systat, etc).

If you employ a rather skilled programmer (steep learning curve!), you may also start from scratch either in S-Plus from ‘Insightful’, or in the – equally powerful open source sftware – R by “The R Project for Statistical Computing”.
If you are interested in PK, you also may go for David Bourne’s Boomer (for Macs, Windows, Linux) and the new graphical interface JGuiB.
A (Bayesian) statistical freeware is WinBugs (with the plugin for PK-analysis PKBUGS).

» Is it also compulsory to validate the WinNonlin software?

Not only WinNonlin, but all software… ;-)
I would not recommend buying one of the pretty expensive “validation packages” offered by the software vendor (some of them are more expensive than the software itself), but applying the classical validation approach:
  • lay down a written validation plan (what will be done – for which purpose – how often<– by whom…)
  • get example data sets (from standard textbooks, NIST, …)
  • set specifications (e.g., maximum deviation of calculated point estimates and confidence limits ±0.01% from reported ones)
  • write an SOP
  • perform the validation according to the SOP
  • revalidate the software every time you update the software and/or the operating system

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2007-01-30 17:44

@ Helmut
Posting: # 497
Views: 12,167
 

 Update (EquivTestPK, Kinetica)

Dear all,

recently I tested EquivTest/PK from ‘statistical solutions’.
Although only acceptance ranges of 0.80-1.25 and 0.70-1.43 do appear in the respective combo-boxes of the program (and are covered in both the manual and the online-help), it’s possible to input any wanted value, therefore e.g., 0.75-1.33 (extended range) and 0.90-1.11 (narrow therapeutic index drugs) can be calculated.

Kinetica v4.4.1:
Implementation of acceptance ranges other than 0.80-1.25/0.70-1.43 (and alpha other than 0.05) was announced by Thermo’s support for the next release of Kinetica.

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2007-04-06 16:43

@ Helmut
Posting: # 643
Views: 12,219
 

 WinNonlin validation

Dear all,

today I found an interesting statement at Pharsight’s support site I want to share with you (WinNonlin FAQ):

Validation and 21 CFR Part 11 Compliance:
2. What is the WinNonlin Validation Kit?
The WinNonlin Validation Kit includes a set of test scripts, which open specific data sets and run a sequence of analytical steps in WinNonlin. The WinNonlin output on the validation machine is captured graphically, and this output is compared pixel-by-pixel with output from the same analysis performed on a reference machine.

So the reference machine computes 2×2=5,
the validation machine computes 2×2=5,
pixels match,
everybody is happy…
:rotfl: :angry:

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2007-07-01 00:45

@ Helmut
Posting: # 855
Views: 11,662
 

 WinNonlin on Windows Vista

Dear all,

another joke from the Far Side:
http://www.pharsight.com/products/prod_winnonlin_req.php states
System requirements for WinNonlin Professional
System software: Minimum Windows® 2000, 2000J, XP or XPJ, or Citrix Meta-Frame XP

But at the Customer Support Site (which is only accessible with a current licence) we find:
Compatibility with Windows Vista
As of May 2007, no current versions of our products have been tested with Windows Vista. Therefore, Vista is not currently a supported operating system. We do however plan to test future release versions on Vista.
  • Micro$oft claims a rank order of its OSs: Vista > XP > W2k > NT4 > …;
  • therefore IMHO Pharsight’s ‘minimum requirements’ should be fulfilled.
  • Vista’s Beta 2 was released in June 2006, RC1 in August 2006, Final (Build 6000) on 08 November 2006, but no time at the Far Side to give it a closer look. :ok:
  • It’s nice to read such a statement after you have paid thousands of dollars for a single license. :clap:
  • I’m running the current Version 5.2 on Vista 6.0.6000 Business (all patches) without any troubles.
  • I’m happy that I did not buy the “Validation Kit” (for an unsupported OS). :sleeping:

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2007-10-15 16:41

@ Helmut
Posting: # 1191
Views: 11,488
 

 WinNonlin still not supported on Vista

Dear all,

Pharsight is working…
Compatibility with Windows Vista
As of September 2007, the following products have been tested on Windows Vista:

Trial Simulator version 2.2.1

Vista is not currently a supported operating system, for any other products not listed above. We do however plan to test future releases on Vista.

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2008-06-07 19:13

@ Helmut
Posting: # 1929
Views: 11,061
 

 WinNonlin still not supported on Vista

Dear all,

although a bug release (5.2.1) came out a couple of days ago, according to the support-site as of May 2008 Vista is still not currently a supported operating system.
Another 8 months went down the drain…
I did not dare installing the new version yet since in the ‘WinNonlin Release Notes 5.2.1’ under the heading ‘Defects corrected in Version 5.2.1’ only 1 page is following, but under ‘Known issues in Version 5.2.1’ 7 pages
I’m not sure whether these issues are just unresolved - or new ones.

Cheers,
Helmut Schütz
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Helmut
Hero
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Homepage
Vienna, Austria,
2008-11-21 01:43

@ Helmut
Posting: # 2755
Views: 10,675
 

 WinNonlin 4.2/5.2.1 will not be supported on Vista

Dear all,

OK, I’m running 5.2.1 on XP Pro SP3 smoothly a couple of months now (and on Vista SP1 with hiccups), but according to the support site (my emphases in red):

Pharsight Products and Windows Vista (general)
Vista Compatibility with Current and Former Product Versions:
According to the applicable Getting Started Guide, System Administrator's Guide, and/or User’s Guide for versions of Pharsight products released prior to 18 September 2008, e.g., PKS 3.1, WinNonlin 4.2, WinNonlin 5.2.1, Windows Vista is not a supported operating system for these product versions. These product versions have not been designed to work with nor fully tested with this new operating system. Pharsight does not intend to perform testing with these existing product versions to determine Vista compatibility, nor to make any corrections to provide for Vista compatibility. However, some of our products may run under Vista with minimal issues.
Vista Compatibility with Future Product Versions:
Pharsight is committed to helping its customers transition smoothly to the new Windows Vista operating system, and will make reasonable commercial efforts to ensure our desktop products are compatible with Vista as soon as practicable. […]

WinNonlin Vista Compatibility:
WinNonlin 5.2.1 was not developed, tested, or certified on the Windows Vista platform. Therefore, we do not officially recommend using WinNonlin with Windows Vista. However, there are several customers that have used WinNonlin with Windows Vista, and it seems to work properly. The officially tested and supported platforms for WinNonlin 5.2.1 are Windows 2000, XP, and 2003. Pharsight does plan to test and support future release versions on Vista, including a planned major release of WinNonlin for 2009 (i.e. version 6.0).


Update (March 2010): WinNonlin 5.3 (Dec 2009) is supported on Vista (32-bit) and Windows 7 platforms (32-bit and 64-bit versions). [Helmut]

Cheers,
Helmut Schütz
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xtianbadillo
Junior

Mexico,
2018-03-01 18:27

@ Helmut
Posting: # 18490
Views: 962
 

 not only WinNonlin...

» If you know a statistician with some programming skills, you may adapt routines in any general-purpose statistical package (e.g., Stata, NCSS, Statistica, SPSS, Minitab, Systat, etc).
done – for which purpose – how often – by whom…)


I know this post could be old (2006), but I was trying Minitab and I discovered that Minitab 18 now it includes Equivalence test for 2x2 crossover. I performed a test Using Data sets A and C from from (Schütz H. AAPS J. 2014 Nov;16(6):1292-7. doi:10.1208/s12248-014-9661-0. Epub 2014 Sep 12.) and this what I got

Dataset A balanced: 90%CI (0.907621, 0.996162)
Dataset C imbalanced: 90%CI (0.394079, 0.870287)

There is no difference against what was reported.
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