Bioequivalence and Bioavailability Forum

Dear guys!

❝ ❝ Interesting. I am not extremely well versed with either package but am curious to learn why this would need be done. Could you explain a little, please?

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❝ I know SAS only from hearsay. From Pharsight’s Support Site:

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Solution for WinNonlin Bioequivalence Warning 11094: Negative final variance component

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❝ The negative final Variance Component warning most likely indicates that, if using Subj(Seq) as a random effect, the within-subject variance (residual) is greater than the between-subject variance. Probably a more appropriate model is to move Subj(Seq) out of the random model and into the fixed model, i.e.,

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❝ Sequence+Subject(Sequence)+Formulation+Period

Sorry. What was the question (see subject line)?

❝ ❝ Is it a convergence/optimizer thing?

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❝ Don’t think so. If you give me some days I will dig out a data set.*

Can play with the data if my SAS is again in reach to me.

Meanwhile I think it is an optimizer thing. Using ML or REML usually implies that variance-covariance terms are fitted with the constraints that they must be >= 0. At least in SAS this is the default setting which must be overred if you want an unconstrained solution. Maybe the WinNonlin doesn't obey this reasonable rule? And therefore the between-subject variance may come out as negative. Or what is meant here?

BTW: Liu & Chow have a chapter dealing with negative between-subject variance in the context of ordinary ANOVA (i.e. using the least square optimizer in fitting the model with all effects fixed). Don't remember the chapter number exactly. This is implemented in Bear I think, see ANOVA_stat.txt "prob: the probability for obtaining a negative estimate of inter-subject variability".

❝ ❝ And would it in SAS be something other than PROC GLM cf. the bogus statement?

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❝ Duno. Detlew?

Sorry. What was the question ?