<div dir="ltr"><div>Thanks Roger,</div><div><br></div><div>So indeed, how many modelers in this group use a similar estimation approach to Roger?</div><div><br></div><div>Please do join this discussion regarding estimation techniques. If enough of us do so, we can write a short summary like we did last year - only this time focus on estimation techniques.</div><div><br></div><div>I hope enough of you will be interested to expose your estimation work for population models this way.</div><div><br></div><div> Jacob</div><div><br></div></div><div class="gmail_extra"><br><div class="gmail_quote">On Thu, Oct 1, 2015 at 4:33 PM, Roger Jelliffe <span dir="ltr"><<a href="mailto:jelliffe@usc.edu" target="_blank">jelliffe@usc.edu</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
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<p class="MsoNormal"><span style="font-size:18pt">Dear Jacob:</span><u></u><u></u></p>
<p class="MsoNormal"><span style="font-size:18pt"> Thanks for your reply. Here is my two cents again.<u></u><u></u></span></p>
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<span style="font-size:18pt">How many in the group use nonparametric methods for population analysis? These methods do not make any assumptions as to the presumed shape of the probability distribution of the model parameters – they are assumption free, and
there are no constraints at all on what that distribution can be. The Pmetrics software by the USC Laboratory of Applied Pharmacokinetics and Bioinformatics makes this software available free over
<a href="http://www.lapk.org" target="_blank"><span style="color:windowtext">www.lapk.org</span></a>. Actually, any system that can be described by ordinary differential equations can be analyzed with this software, not just pharmacokinetic/dynamic systems.
In addition, they permit maximally precise control of the system (dosage regimens of drugs, for example) using multiple model (MM) dosage design. At the web site, you can also access publications and technical reports dealing with the subject. For openers,
one might look at these references:</span><u></u><u></u></p>
<p><span style="font-family:"Calibri","sans-serif";font-size:18pt">1.</span><span style="font-size:7pt">
</span><span style="font-family:"Calibri","sans-serif";font-size:18pt"> Bustad A, Terziivanov D, Leary R, Port R, Schumitzky A, and Jelliffe R: Parametric and Nonparametric Population Methods: Their Comparative Performance in Analysing a Clinical Data Set
and Two Monte Carlo Simulation Studies. Clin. Pharmacokinet., 45: 365-383, 2006.</span><u></u><u></u></p>
<p><span style="font-family:"Calibri","sans-serif";font-size:18pt">2.</span><span style="font-size:7pt">
</span><span style="font-family:"Calibri","sans-serif";font-size:18pt">Neely M, van Guilder M, Yamada W, Schumitzky A, and Jelliffe R: Accurate Detection of Outliers and Subpopulations with Pmetrics, a Nonparametric and Parametric Pharmacometric Modeling
and Simulation Package for R. Therap. Drug Monit. 34: 467-476, 2012.</span><u></u><u></u></p>
<p><span style="font-family:"Calibri","sans-serif";font-size:18pt">3.</span><span style="font-size:7pt">
</span><span style="font-family:"Calibri","sans-serif";font-size:18pt">Jelliffe R, Schumitzky A, Bayard D, Milman M, Van Guilder M, Wang X, Jiang F, Barbaut X, and Maire P: Model-Based, Goal-Oriented, Individualized Drug Therapy: Linkage of Population Modeling,
New "Multiple Model" Dosage Design, Bayesian Feedback, and Individualized Target Goals. Clin. Pharmacokinet. 34: 57-77, 1998.</span><u></u><u></u></p>
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<span style="font-size:18pt">Likelihoods are greater with NP models because the distributions are not constrained by any assumptions about its shape, such as normal, lognormal, bimodal, etc. The distributions simply are what they are. There is also a good
Monte Carlo simulation routine that can do rigorous MC simulation even when the basic discrete structure of a nonparametric model with its multiple discrete support points is preserved.</span><u></u><u></u></p>
<p class="MsoNormal"><span style="font-size:18pt">Best regards to all,</span><u></u><u></u></p>
<p class="MsoNormal"><span style="font-size:18pt">Roger Jelliffe</span><u></u><u></u></p>
<p class="MsoNormal"><span style="font-size:18pt"> </span><u></u><u></u></p>
<p class="MsoNormal"><span style="color:red;font-size:18pt"><u></u> <u></u></span></p>
<p class="MsoNormal"><u></u> <u></u></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Roger W. Jelliffe, M.D., F.C.P., F.A.A.C.S.<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Professor of Medicine Emeritus,<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">USC School of Medicine<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Founder and Director Emeritus<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Laboratory of Applied Pharmacokinetics and Bioinformatics<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Consultant in Infectious Diseases,
<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Children’s Hospital of Los Angeles<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">4640 Hollywood Blvd, MS #30<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Los Angeles CA 90027<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Office - 323-361-5046<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Fax - 323-361-5045<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Cell - 626-484-5313<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt"><a href="mailto:jelliffe@usc.edu" target="_blank">jelliffe@usc.edu</a><u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt"><a href="http://www.lapk.org" target="_blank">www.lapk.org</a><u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt"><u></u> <u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">Quantitative approaches<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">to optimally precise individualized drug therapy<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">are more caring,<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">and useful,<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">scientifically, medically and socially,<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">than all the memorized words and facts<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">of categorized and classified experience<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-family:"Arial","sans-serif";font-size:12pt">can ever be!<u></u><u></u></span></p>
<p class="MsoNormal"><u></u> <u></u></p>
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