Re: Change of NSIG or R matrix
Yes, it should be fine to use S matrix if you cannot get default to run, and use NSIG larger or smaller than default value of 3 (although this is not guaranteed, usually NSIG does not change the OF value or parameter estimates in any significant way). Note that Nonmem manual recommends that SIGL >= 3*NSIG, TOL >= SIGL. Separate SIGL can be set on COV step, and it is recommended that SIGL >= 4*NSIG on COV step. In real life I've seen many examples where larger NSIG and SIGL resulted in successful COV step, and also many examples when default values were better (in getting COV step). UNCONDITIONAL on COV step allows you to run COV even when minimization ended with some error.
Contrary to Nick's experience, I found that COV step is useful as it reveals which of the model parameters are poorly estimated, and that CI based on SE are usually quite good and are in a general agreement with the bootstrap CI, but it may depend on the problem.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 10/8/2013 3:57 AM, Xinting Wang wrote:
> Dear all,
>
> I have a naive question regarding the modeling building process in
> NONMEM. With more and more covariates added in the model, I often come
> across an error message saying that "ERROR 134", or R MATRIX SINGULAR.
>
> After searching from the internet, I learned that changing NSIG in
> $ESTIMATION and MATRIX=S in $COV would be helpful for both problems
> respectively. And from my own experience, it dose help with the modeling
> building.
>
> However, my concern is, I used different NSIG and MATRIX in the previous
> steps. Is it proper to use different NSIGs and MATRICE in a single model
> building? If not, could you please explain this a little bit?
>
> Thank you in advance!
>
> Best Regards
> --
> Xinting
> Wang