RE: TVKa>TVKe or Ka>Ke?

From: Ken Kowalski <Ken.Kowalski@pfizer.com> Subject: RE: [NMusers] TVKa>TVKe or Ka>Ke? Date: 8/7/2003 1:32 PM All, This parameterization (TVKA>TVKE) will ensure that the population estimates don't flip-flop. At the individual level flip-flop might still occur. Flip-flop at the individual level is more likely to occur when the population estimates for ka and ke are fairly close relative to the IIV. If we have about an order of magnitude difference between ka and ke and the IIV for ka, CL, and V are not too large we are less likely to have flip-flop. Still, it is probably good practice to routinely monitor these estimates to ensure that flip-flop is not occurring. Rik raises a good point, however. So, as a first step, it might be good to guard against flip-flop at the population level. If that works and provides sufficient stability so that flip-flop doesn't occur at the individual level, then this might be an attractive parameterization because you can still get a population estimate and IIV for ka directly. If flip-flop is still an issue at the individual level, then further constraining the model at the individual level (ka>ke) might be considered and sacrifice (at least directly) getting population estimates of ka and its IIV. Ken