Bioequivalence and Bioavailability Forum 19:00 CEST

Main page Policy/Terms of Use Abbreviations Latest Posts

 Log in |  Register |  Search

ElMaestro
Hero

Denmark,
2015-06-03 17:57

Posting: # 14905
Views: 6,281
 

 Kinetica [Software]

Hi all,

"BSWP response to letter received from Dr Fuglsang regarding Kinetica software used in BE studies (EMA/1085 07/2015). The CHMP discussed the BSWP response and concluded that no medically relevant impact could be observed following the assessed studies. The Committee agreed that a response to CMDh should be drafted by BSWP as well as a response letter to Dr Fuglsang."

I tried to read the sentence a few times but I am not convinced I understand what they are actually saying. If I get it right there is no problem. I can live with that as I am not on a personal crusade against anything or anyone. Haha I am just a scientist and not even a good one at that.

Most of us have been involved in handling of narrowly failing drugs. The acceptance range 80.00%-125.00% is very strictly enforced. Two decimals. And that's it.

I am under the impression that the error introduced by Kinetica on the PE can be somewhat higher than that zero tolerance regulators enforce. Is that not a little strange? Perhaps I should just put this entire story into the odd sock drawer and consider it another curiosum which I can't fathom much like Conchita Wurst, the Danish soccer championsship in 1992, or the reason why anyone would wish to put raisins or cornflakes inside RitterSport?


Edit: Category changed. [Helmut]

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
d_labes
Hero

Berlin, Germany,
2015-06-03 19:03

@ ElMaestro
Posting: # 14906
Views: 5,354
 

 Kinetica

Öberster großer Meister!

We know already the (published) opinion of some well known member of the PKWP. Seems statisticians of the EMA (BSWP) are adepts of his opinion.

I'm curious why. Scientifically!

It's a pitty that we don't know a counter example.
In my gut feeling there must be some! Remenber our discussion that Kinetica is Number three?

Any body out there used Kinetica in unbalanced studies? I promise you full anonymity :yes:.

ElMaestro: Let us be informed if you could identify some "Why's". Scientifically!
Some insight from Helmut's presentation in Prague?

Regards,

Detlew
ElMaestro
Hero

Denmark,
2015-06-03 20:15

@ d_labes
Posting: # 14909
Views: 5,373
 

 Kinetica

Hi again,

» It's a pitty that we don't know a counter example.
» In my gut feeling there must be some! Remenber our discussion that Kinetica is Number three?

There are tons of studies evaluated with Kinetica. Usually CROs write that stuff on their homepage. But with the publications by the Dynamic Trio CROs seem to be less enthusiastic about mentioning Kinetica. And it does take some time to decide to buy another package.

» Any body out there used Kinetica in unbalanced studies? I promise you full anonymity :yes:.

Difficult for a CRO to come forward possibly? But Sponsors might if they had failed studies that could be potentially passing?! Remains to be seen.
Couldn't it be simulated? I think we know the equations used normally and by TFS. We could simulate some scenarios and count the frequency by which the wrong decision is taken. I could write this stuff in a few days. You could probably do it quicker. But I have no good idea on how to use the result?

» ElMaestro: Let us be informed if you could identify some "Why's". Scientifically!

I like the idea but must admit I simply don't know how to get answers to those why's. I feel I am not well-connected to the extent that I can ask.

» Some insight from Helmut's presentation in Prague?

Helmut's talk was about validation and served as great inspiration. It did not touch so much on Kinetica but contained a wealth of other info.

While we are at it:
When I audit CROs I often ask if they rely on automated IQ/OP/PQ. They usually say they validate formally with a plan and approvals and signatures and coffee and cake and IQ/OQ/PQ scripts. When I ask them if they have checked if some of those scripts contain anything relevant to BE the answer is no. Always.
You can look up in ICH E6 that software must perform for the intended purpose (clause 5.5.3.)
If you buy a pair of shoes you check that they fit your feet, right?

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2015-06-04 01:07

@ ElMaestro
Posting: # 14911
Views: 5,376
 

 Kinetica ☠

Dear both,

seems that you are having fun!

» » In my gut feeling there must be some! Remenber our discussion that Kinetica is Number three?

Since Kinetica is widely-used in the Middle East I’m in contact with regulators from Saudi Arabia and Oman, who are exploring the issue since last October. They confirmed the defect imme­di­a­tely. From the information given in the “Thermo Scientific Informatics Support Resource Center” (see this post) I seriously suspected that only the crossover defect was cor­rected (our second paper was not mentioned). Ten days ago I got a response from statisticians of the SFDA (THX!). They com­pared our re­fe­rence data sets in Phoenix 6.3 to the new “Service Release 1” of Kinetica 5.1 (of Dec 24, 2014).

Bingo!
Imbalanced crossovers are OK (PE and 90% CI).
[image]Of course, the test for se­quence effects in cross­overs (here) and the CVs (there) is as flawed as it ever was.
Parallel designs with un­equal group sizes are still wrongly calculated (exactly the “old” results…).


» You can look up in ICH E6 that software must perform for the intended purpose (clause 5.5.3.)

Don’t forget Annex III to Procedure for Conducting GCP Inspections requested by the EMEA: Computer Systems (2007), which is a one-pager leading to the very exhaustive PIC/S Guidance: Good Practices for Computerised Systems in Regulated “GXP” Environments (2007)

Cheers,
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
nobody
Senior

2015-06-03 19:26

@ ElMaestro
Posting: # 14907
Views: 5,372
 

 Kinetica

Ritter Sport Knusper and Traube Nuss are my absolute favourites!

Besides this here, so so sad, but so so true...

https://www.youtube.com/watch?v=9FnO3igOkOk









...at least Mr. Blatter has quit

Kindest regards, nobody
d_labes
Hero

Berlin, Germany,
2015-06-03 20:06

@ nobody
Posting: # 14908
Views: 5,321
 

 OT

» ...at least Mr. Blatter has quit

And nobody is there to muck out ...

Regards,

Detlew
ElMaestro
Hero

Denmark,
2015-06-03 20:16

@ nobody
Posting: # 14910
Views: 5,307
 

 Kinetica

Dear nobody,

» Ritter Sport Knusper and Traube Nuss are my absolute favourites!

I am seriously beginning to have doubts about your sanity.:-D

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
nobody
Senior

2015-06-04 08:01

@ ElMaestro
Posting: # 14912
Views: 5,233
 

 Kinetica

Just to relpy to the Austrian-Saudi perspective: EU documents often start to make sense when you replace "medical" by "political"...

Kindest regards, nobody
Back to the forum Activity
 Thread view
Bioequivalence and Bioavailability Forum |  Admin contact
18,700 posts in 3,984 threads, 1,241 registered users;
online 19 (0 registered, 19 guests [including 10 identified bots]).

When puzzled, it never hurts to read the primary documents –
a rather simple and self-evident principle that has, nonetheless,
completely disappeared from large sectors
of the American experience.    Stephen Jay Gould

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
HTML5 RSS Feed