Re: NMVI and SEs assessment
Bernard
The bootstrap method is intended to give you a reliable measurement of the
uncertainty of the estimates. The interest is then to obtain, for example, the
median and the 95% confidence interval of estimates via the 2.5th and 97.5th
quantiles of each parameter. So I think it is not really necessary to look at
the bootstrap statistics on the SEs produced by the Nonmem output (in my
experience and probably that of other users, SEs produced by Nonmem may vary
with initial values, or the $COV step can be achieved or not also depending on
initial estimates). I personally use to remove the $COV when I do a bootstrap
via WfN
Hope that it heps
Saik
----- Original Message -----
Quoted reply history
From: Bernard ROYER
To: [email protected]
Sent: Wednesday, April 23, 2008 11:01 AM
Subject: [NMusers] NMVI and SEs assessment
Dear NMusers,
I have questions about bootstraping and NONMEM VI assement of SEs.
I have developed a 2-compartment PK model using NMVI that converged with
estimations of THETAs and OMEGAs. The predictive check simulations indicated
that the model satisfactorily described the data with parameters estimated by
NMVI. Then I started the assement of SEs by boostrating the data using WFN
(1000 resamplings). I found similar results for THETAs, OMEGAs and SIGMAs (mixt
error used). About the results of SEs, I also found similar results for the SEs
of THETA1 (Volume), THETA2 (Clearance), OMEGAs and SIGMA1 (proportional part),
but not for the SEs of THETA3 nor THETA4 (K12 and K21) and the SIGMA2 (residual
error). I think that the actual values are more close of those obtained with
bootstrap than those obtained with NMVI.
The results of the obtained SEs are described in the table below. I also
performed a run with the same Input and data set with NMV and the results are
also described in the table (NMV gives same results for thetas, omegas, sigmas
and OFV).
SE of: NMVI values Bootstrap values NMV values
THETA1 0.148 0.154 0.154
THETA2 0.00218 0.00242 0.0227
THETA3 0.00063 0.0013 0.0013
THETA4 0.00036 0.0022 0.0019
OMEGA1 0.0094 0.0095 0.0094
OMEGA2 0.0050 0.0054 0.0051
SIGMA1 0.0063 0.0064 0.0064
SIGMA2 0.675 0.946 0.832
My questions are:
- Why NMVI gives evaluations of SE less reliable than NMV ? and why only for
THETA3, THETA4 and SIGMA 1
- for covariates determination wiht NMVI, do I need to perform bootstrap for
each covariate or taking into account the decrease of omega is sufficient ?
- The value of residual error obtained with NMVI is 1.69 (SE = 0.675). The
value obtained with boostrap is 1.58 (SE = 0.95), thus zero is included in
IC95. How interpreting residual error including zero in IC95 with boostrap but
not with NMVI. Removing SIGMA2 leads to failure of the run. Should I fix this
value or leaving it with its SE ?
Bernard Royer
Pharmacology Dpt
University Hospital
Besancon, France