PVRC
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India,
2021-04-23 05:24
(20 d 22:10 ago)

Posting: # 22312
Views: 343
 

 Missing three consecutive samples in the elimination phase [Study Per­for­mance]

Dear All,

I have a question on the inclusion of a subject with missing three consecutive sampling points in the elimination phase. The subject followed the procedures through 8 hr sampling points and left for an emergency. The half life of the drug is 12 hours. the subject is willing to join the next periods. Whether that subject will be included in the PK analysis and /or statistical analysis if allowed in the next periods ?

Thanks in advance

with best regards

PVRC


Edit: Category changed; see also this post #1[Helmut]
ElMaestro
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Denmark,
2021-04-23 06:40
(20 d 20:54 ago)

@ PVRC
Posting: # 22313
Views: 298
 

 Missing three consecutive samples in the elimination phase

Hi PVRC,

» I have a question on the inclusion of a subject with missing three consecutive sampling points in the elimination phase. The subject followed the procedures through 8 hr sampling points and left for an emergency. The half life of the drug is 12 hours. the subject is willing to join the next periods. Whether that subject will be included in the PK analysis and /or statistical analysis if allowed in the next periods ?

Isn't that the wrong question?
I mean why would you include the subject for period 2 if not using her/his data? For production of tolerance/safety data only?

The question is more likely whether or not the subject should be invited to complete the study. I think she/he should, if you can make of her/his data. Three missings in the elimination phase is not a show-stopper, however annoying it may be. If you do not have SOPs or a protocol that somehow provides for exclusion I think the subject is still in the study.
At some CROs a subject going home in period 1 on own will or due to an AE is a lost/discontinued subject, while at other CROs subjects can come back for period 2 in such cases. It isn't a situation that is well defined by guidance.

Good luck with the rest of the study.
:-)

Pass or fail!
ElMaestro
PVRC
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India,
2021-04-23 08:19
(20 d 19:14 ago)

@ ElMaestro
Posting: # 22314
Views: 290
 

 Missing three consecutive samples in the elimination phase

Hi ElMaestro,

Thank you for the reply,

» The question is more likely whether or not the subject should be invited to complete the study. I think she/he should, if you can make of her/his data. Three missings in the elimination phase is not a show-stopper, however annoying it may be.

If the AUC0-t is not affected by the missing sample in the elimination phase can the data from such a subject be considered for analysis..?

with best regards

PVRC
Helmut
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Vienna, Austria,
2021-04-23 08:34
(20 d 18:59 ago)

@ PVRC
Posting: # 22316
Views: 287
 

 Suggestions

Hi PVRC,

» If the AUC0-t is not affected by the missing sample in the elimination phase can the data from such a subject be considered for analysis..?

What does your protocol say? It boils down how long you sampled. See also this article, esp. the section about Missings.

With a half life of 12 hours and the last sample at 8 hours in the first period, a comparison of AUC0–t will be biased. Essentially you have two options:
  1. Compare in this subject AUC0–8 (see also this post).
  2. Exclude the subject from the comparison of AUC but keep him/her for the comparison of Cmax. Since commonly studies are powered for Cmax with its higher variability, the impact on power of AUC is a minor one.

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Ohlbe
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France,
2021-04-23 12:50
(20 d 14:44 ago)

@ PVRC
Posting: # 22321
Views: 274
 

 Missing three consecutive samples in the elimination phase

Dear PVRC,

» The subject followed the procedures through 8 hr sampling points and left for an emergency. The half life of the drug is 12 hours.

What we're missing here is the expected tmax. What does the reference information of the reference product say ? If you have past experience on the same active substance, what was the latest tmax you had ?

You might keep the subject and use his data for Cmax but not for AUC. Considering the little impact that one single subject will have on power, I would however rather consider him as a drop out and avoid potential nasty discussions. This being said, if this is for the same 4-treatment William's design study for which you posted other messages today, it might be possible to exclude this period and keep his data for the other 3. If so, this must be defined and documented now, before the next period.

Regards
Ohlbe
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