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RegisterDose proportionality using Power Model [Regulatives / Guidelines]
Hello,
I have a few questions with regard to the following paragraph from EMA's BE guideline:
In case of non-linear pharmacokinetics (i.e. not proportional increase in AUC with increased dose) there may be a difference between different strengths in the sensitivity to detect potential differences between formulations. In the context of this guideline, pharmacokinetics is considered to be linear if the difference in dose-adjusted mean AUCs is no more than 25% when comparing the studied strength (or strength in the planned bioequivalence study) and the strength(s) for which a waiver is considered. In order to assess linearity, the applicant should consider all data available in the public domain with regard to the dose proportionality and review the data critically. Assessment of linearity will consider whether differences in dose-adjusted AUC meet a criterion of ± 25%.
There are a lot of discussion on the topic of linearity/proportionality in the forum, I read in one of the topic using power model.
Can pls explain for the same some little bit clarity on “Power Model".
log(Cmax) = µ + [β x log(Dose)] In that equation where we can get µ & β and confidence intervals (The dose proportionality was confirmed if the 90% CI of β (βl, βu))
Also can you halp for is there any sas code the same (any papers/journals/ references etc.,)
I have a few questions with regard to the following paragraph from EMA's BE guideline:
In case of non-linear pharmacokinetics (i.e. not proportional increase in AUC with increased dose) there may be a difference between different strengths in the sensitivity to detect potential differences between formulations. In the context of this guideline, pharmacokinetics is considered to be linear if the difference in dose-adjusted mean AUCs is no more than 25% when comparing the studied strength (or strength in the planned bioequivalence study) and the strength(s) for which a waiver is considered. In order to assess linearity, the applicant should consider all data available in the public domain with regard to the dose proportionality and review the data critically. Assessment of linearity will consider whether differences in dose-adjusted AUC meet a criterion of ± 25%.
There are a lot of discussion on the topic of linearity/proportionality in the forum, I read in one of the topic using power model.
Can pls explain for the same some little bit clarity on “Power Model".
log(Cmax) = µ + [β x log(Dose)] In that equation where we can get µ & β and confidence intervals (The dose proportionality was confirmed if the 90% CI of β (βl, βu))
Also can you halp for is there any sas code the same (any papers/journals/ references etc.,)
Complete thread:
- Dose proportionality using Power ModelPandu 2015-07-12 12:55
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- EMA Dose proportionality d_labes 2015-07-13 08:19
Ing. Helmut Schütz