Dose Proportionality and Variance [Study As­sess­ment]

posted by AngusMcLean – USA, 2016-05-11 16:55  – Posting: # 16294
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We have completed a dose proportionality study using the lowest strength to the highest strength of a modified release formulation of a class I drug. The approach used was the usual cross-over design with 20 subjects (AB, BA) and dose normalized the PK parameters Cmax and AUC0-T prior to bioequivalence. No problem we are BE comfortably within the limits (0.8-1.25). I use Phoenix WinNonlin V6.4 so the within subject and between subject variance values for Cmax and AUC0-t appear in the output.

Another worker has used the power model with the same data set for dose proportionality as described by Brian Smith in Pharmaceutical Research in year 2000. The paper is entitled "Confidence Interval Criteria for Assessment of Dose Proportionality". The point estimates are much the same as my approach, but he quotes 98% CI. His CI values are also within the lmits.

This worker has also calculated within subject and between subject variance values for the parameters. There are large differences for the values of within subject variance compared with my approach, but the between subject variance values are very similar for both Cmax and AUC. Should the within subject and between subject variance values of Cmax and AUCC0-t be very similar for both approaches?

Angus


Edit: Category changed; see also this post #1. Please don’t shout! [Helmut]

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