GM
★    

India,
2018-07-30 11:57
(816 d 20:27 ago)

Posting: # 19116
Views: 3,117
 

 Outlier Tests [Outliers]

Hello All,

Hope all are doing well..!!!

Which outlier tests can apply for in vitro studies? Is there any specifications for this?

Whether we can apply the studentized outlier test for in vitro data...? If not please explain the reason.

I was searched for the reasons and which tests can apply for in vitro/in vitro studies in this forum as well as in the Google. But didn't get the proper idea.

Kindly suggest me something on this.

Thanks in advance.

Regards,
GM.

Best Regards,
GM
GM
★    

India,
2019-02-14 06:24
(618 d 02:00 ago)

@ GM
Posting: # 19912
Views: 2,028
 

 Outlier Tests

Hello All,

Hope all are doing well..!!!

» Which outlier tests can apply for in vitro studies? Is there any specifications for this?
»
» Whether we can apply the studentized outlier test for in vitro data...? If not please explain the reason.

Thanks in advance.

Best Regards,
GM
ElMaestro
★★★

Belgium?,
2019-02-14 08:27
(617 d 23:57 ago)

(edited by ElMaestro on 2019-02-14 08:44)
@ GM
Posting: # 19913
Views: 2,036
 

 Outlier Tests

Hello GM,

and thank for your patience :-D

» Which outlier tests can apply for in vitro studies? Is there any specifications for this?
»
» Whether we can apply the studentized outlier test for in vitro data...? If not please explain the reason.

I don't think this is an area covered very well by guidelines and I am not entirely sure there is a need either.
If you are really hardcore you can look at distribution theory for the points on the time series and then derive critical values; this is in line with the thinking behind studentized residuals for normally distributed data. I have no idea if this would be accepted, but it would at least be very stringent.

If you are softcore, take one step back and ask your self what the impact of outliers is: They increase variability. And for that you have guidance or at least some regulatory practice and precedent to lean on.
When variability goes up, the classical f2 comparison may not be valid and you'll need to provide proof via bootstrapping of f2 that the profiles are similar. Mahalanobis distance was also in play until recently but it went out of fashion. It was simply too difficult to spell and pronounce for Europeans, I believe :-).

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.
GM
★    

India,
2019-02-14 18:08
(617 d 14:16 ago)

@ ElMaestro
Posting: # 19922
Views: 1,966
 

 Outlier Tests

Hi Elmaestro,

Thankyou for the reply.

» and thank for your patience :-D

:ok:

» I don't think this is an area covered very well by guidelines and I am not entirely sure there is a need either.

Yes... there is no clear guidelines on this topic.

» If you are really hardcore you can look at distribution theory for the points on the time series and then derive critical values; this is in line with the thinking behind studentized residuals for normally distributed data. I have no idea if this would be accepted, but it would at least be very stringent.
»
» If you are softcore, take one step back and ask your self what the impact of outliers is: They increase variability. And for that you have guidance or at least some regulatory practice and precedent to lean on.
» When variability goes up, the classical f2 comparison may not be valid and you'll need to provide proof via bootstrapping of f2 that the profiles are similar. Mahalanobis distance was also in play until recently but it went out of fashion. It was simply too difficult to spell and pronounce for Europeans, I believe :-).

Our in vitro studies are not dissolution studies. These are in vitro permeation studies. In these studies variability is high when compared to in vivo studies. Sample size is small when compared with in vivo studies. In this case, every value will impact the study results. So how can we deal this data, when outliers are present in the data?

One more thing, generally FDA guidance allows us to prove BE on log transformed data. So, on which data outlier test will be performed(either original scale or log scale)?

Thoughts on this topic is highly appreciated.

Thankyou in advance.

Best Regards,
GM
ElMaestro
★★★

Belgium?,
2019-02-14 21:11
(617 d 11:13 ago)

@ GM
Posting: # 19923
Views: 1,974
 

 Outlier Tests

Hello GM,

» Our in vitro studies are not dissolution studies. These are in vitro permeation studies. In these studies variability is high when compared to in vivo studies. Sample size is small when compared with in vivo studies. In this case, every value will impact the study results. So how can we deal this data, when outliers are present in the data?

I apologise, I automatically thought it was dissolution and I should not have assumed this.
I don't quite know hwo to deal with it. Find a data expert, do some serious juggling of the figures, approach FDA with a controlled correspondence. No time, no budget, client impatient? Do it anyway :-)

» One more thing, generally FDA guidance allows us to prove BE on log transformed data. So, on which data outlier test will be performed(either original scale or log scale)?

I am not too much into these studies, but if FDA allow a parametric evaluation on log data then usually it means you are looking for outliers on the log scale. May I don't mean "usually" but "always", probably, I can't think of any case where this wasn't the case.

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.
GM
★    

India,
2019-02-15 03:58
(617 d 04:26 ago)

@ ElMaestro
Posting: # 19924
Views: 1,947
 

 Outlier Tests

Dear Friends,

Any data expert, please help me on this topic.

We have no time to consult the agency with regards to outliers in in vitro permeation studies and there is no clear guideline from the agency.

Thank you in advance

Best Regards,
GM
Activity
 Admin contact
21,179 posts in 4,414 threads, 1,475 registered users;
online 7 (0 registered, 7 guests [including 1 identified bots]).
Forum time: Saturday 08:25 UTC (Europe/Vienna)

It is the peculiar and perpetual error of the human understanding
to be more moved and excited by affirmatives than negatives.    Francis Bacon

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5