Population PKPD Mode.. - Pharsight Corporation
Population PKPD Mode.. - Pharsight Corporation
Population PKPD Mode.. - Pharsight Corporation
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When to use diagnostics ?<br />
●<br />
●<br />
●<br />
Basic<br />
• Confirm convergence : numerical checks<br />
• Check if we had some improvement (OFV lower, BSV on parameter lower, residual<br />
variability lower…)<br />
Key runs<br />
• Unusual covariate detected : confirm with randomization test<br />
• Depends on the importance of the run<br />
Final run<br />
• Extensive diagnostics<br />
• Check if we have influential individuals<br />
♦ Individual contributions to OFV + fits with and without the suspect individuals<br />
♦ Case deletion diagnostics, Jackknifing<br />
• Check if we have outliers ( data with |WRES| > 4) compare fit with and without outliers<br />
• Check if parameters are precise not on a boundary and plausible<br />
♦ Standard errors may be obtained<br />
- Asymptotically from covariance step: always symmetric may contain impossible<br />
values<br />
- From bootstrap: time consuming<br />
- From likelihood profiling : time consuming poor if LRT not applicable and if<br />
likelihood approximation is far from the true likelihood<br />
• Check if the model describe the observed data well (PPC)<br />
slide 45<br />
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