Shatha
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2022-08-27 03:36
(548 d 16:22 ago)

Posting: # 23237
Views: 1,539
 

 AUCtau and Ctau calculation [Study As­sess­ment]

Hello

I performed NCA analysis for concentration data at steady state:

(AUCtau, Ctau, and fluctuation) PK parameters were missing for some subjects who gave the last sample (at tau) earlier than scheduled.
Upon checking: WinNonlin was not able to calculate Lambda_z for those subjects (using best fit method) since each of them has only one sample after Tmax.
Accordingly, WinNonlin didn't perform extrapolation and was unable to calculate the mentioned steady state parameters.
Can we induce lambda_z calculation using two sampling points only (Tmax and Tlast)? Will this be acceptable by the authorities (specifically: the European authorities)? any other possible solutions?

Also, few subjects have missing lambda_z for another reason (concentrations were still increasing at tau).
Shall we exclude them from statistical analysis? In this case, the sampling time deviation (early collection of the sample) will be the main cause for excluding the subject.
Or shall we replace the actual time with the theoretical time (tau)?

As a note: WinNonlin has calculated AUCTtau and Ctau for subjects with missing samples at tau. Is it acceptable to exclude such subjects from statistical analysis?

Thank you


Edit: Category changed; see also this post #1 and #4[Helmut]
Helmut
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2022-08-27 12:24
(548 d 07:34 ago)

@ Shatha
Posting: # 23238
Views: 1,165
 

 SAP?

Hi Shata,

before I will go into the details: What does your protocol say?

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Shatha
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2022-08-27 13:55
(548 d 06:03 ago)

@ Helmut
Posting: # 23239
Views: 1,201
 

 SAP?

Hi Helmut:

❝ before I will go into the details: What does your protocol say?


My protocol requests to use actual sampling times for analysis and lists Ctau and AUCtau as primary PK parameters.
The following are mentioned as possible reasons for exclusion:
*Data from subjects with missing concentration values (missed blood draws, lost samples, samples unable to be quantified, etc.) may be used if some of the PK parameters can be estimated using the remaining data points. Otherwise, data from these subjects will be excluded from the final analysis.
*Subjects, whose bio-analysis data do not provide a complete PK profile, should be excluded from bio-assessment.

No further related information is covered in the protocol and there is no separate SAP.

Thanks
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