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<!DOCTYPE html>
<!-- Generated by pkgdown: do not edit by hand --><html lang="en"><head><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta charset="utf-8"><meta http-equiv="X-UA-Compatible" content="IE=edge"><meta name="viewport" content="width=device-width, initial-scale=1.0"><title>Fit nonlinear mixed models with SAEM — saem • mkin</title><!-- jquery --><script src="https://cdnjs.cloudflare.com/ajax/libs/jquery/3.4.1/jquery.min.js" integrity="sha256-CSXorXvZcTkaix6Yvo6HppcZGetbYMGWSFlBw8HfCJo=" crossorigin="anonymous"></script><!-- Bootstrap --><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/twitter-bootstrap/3.4.1/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous"><script src="https://cdnjs.cloudflare.com/ajax/libs/twitter-bootstrap/3.4.1/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script><!-- bootstrap-toc --><link rel="stylesheet" href="../bootstrap-toc.css"><script src="../bootstrap-toc.js"></script><!-- Font Awesome icons --><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/font-awesome/5.12.1/css/all.min.css" integrity="sha256-mmgLkCYLUQbXn0B1SRqzHar6dCnv9oZFPEC1g1cwlkk=" crossorigin="anonymous"><link rel="stylesheet" href="https://cdnjs.cloudflare.com/ajax/libs/font-awesome/5.12.1/css/v4-shims.min.css" integrity="sha256-wZjR52fzng1pJHwx4aV2AO3yyTOXrcDW7jBpJtTwVxw=" crossorigin="anonymous"><!-- clipboard.js --><script src="https://cdnjs.cloudflare.com/ajax/libs/clipboard.js/2.0.6/clipboard.min.js" integrity="sha256-inc5kl9MA1hkeYUt+EC3BhlIgyp/2jDIyBLS6k3UxPI=" crossorigin="anonymous"></script><!-- headroom.js --><script src="https://cdnjs.cloudflare.com/ajax/libs/headroom/0.11.0/headroom.min.js" integrity="sha256-AsUX4SJE1+yuDu5+mAVzJbuYNPHj/WroHuZ8Ir/CkE0=" crossorigin="anonymous"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/headroom/0.11.0/jQuery.headroom.min.js" integrity="sha256-ZX/yNShbjqsohH1k95liqY9Gd8uOiE1S4vZc+9KQ1K4=" crossorigin="anonymous"></script><!-- pkgdown --><link href="../pkgdown.css" rel="stylesheet"><script src="../pkgdown.js"></script><meta property="og:title" content="Fit nonlinear mixed models with SAEM — saem"><meta property="og:description" content="This function uses saemix::saemix() as a backend for fitting nonlinear mixed
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    <div class="page-header">
    <h1>Fit nonlinear mixed models with SAEM</h1>
    <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/R/saem.R" class="external-link"><code>R/saem.R</code></a></small>
    <div class="hidden name"><code>saem.Rd</code></div>
    </div>

    <div class="ref-description">
    <p>This function uses <code><a href="https://rdrr.io/pkg/saemix/man/saemix.html" class="external-link">saemix::saemix()</a></code> as a backend for fitting nonlinear mixed
effects models created from <a href="mmkin.html">mmkin</a> row objects using the Stochastic Approximation
Expectation Maximisation algorithm (SAEM).</p>
    </div>

    <div id="ref-usage">
    <div class="sourceCode"><pre class="sourceCode r"><code><span><span class="fu">saem</span><span class="op">(</span><span class="va">object</span>, <span class="va">...</span><span class="op">)</span></span>
<span></span>
<span><span class="co"># S3 method for mmkin</span></span>
<span><span class="fu">saem</span><span class="op">(</span></span>
<span>  <span class="va">object</span>,</span>
<span>  transformations <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"mkin"</span>, <span class="st">"saemix"</span><span class="op">)</span>,</span>
<span>  degparms_start <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/numeric.html" class="external-link">numeric</a></span><span class="op">(</span><span class="op">)</span>,</span>
<span>  test_log_parms <span class="op">=</span> <span class="cn">TRUE</span>,</span>
<span>  conf.level <span class="op">=</span> <span class="fl">0.6</span>,</span>
<span>  solution_type <span class="op">=</span> <span class="st">"auto"</span>,</span>
<span>  nbiter.saemix <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">300</span>, <span class="fl">100</span><span class="op">)</span>,</span>
<span>  control <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span>displayProgress <span class="op">=</span> <span class="cn">FALSE</span>, print <span class="op">=</span> <span class="cn">FALSE</span>, nbiter.saemix <span class="op">=</span> <span class="va">nbiter.saemix</span>,</span>
<span>    save <span class="op">=</span> <span class="cn">FALSE</span>, save.graphs <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span>
<span>  fail_with_errors <span class="op">=</span> <span class="cn">TRUE</span>,</span>
<span>  verbose <span class="op">=</span> <span class="cn">FALSE</span>,</span>
<span>  quiet <span class="op">=</span> <span class="cn">FALSE</span>,</span>
<span>  <span class="va">...</span></span>
<span><span class="op">)</span></span>
<span></span>
<span><span class="co"># S3 method for saem.mmkin</span></span>
<span><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">x</span>, digits <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/Extremes.html" class="external-link">max</a></span><span class="op">(</span><span class="fl">3</span>, <span class="fu"><a href="https://rdrr.io/r/base/options.html" class="external-link">getOption</a></span><span class="op">(</span><span class="st">"digits"</span><span class="op">)</span> <span class="op">-</span> <span class="fl">3</span><span class="op">)</span>, <span class="va">...</span><span class="op">)</span></span>
<span></span>
<span><span class="fu">saemix_model</span><span class="op">(</span></span>
<span>  <span class="va">object</span>,</span>
<span>  solution_type <span class="op">=</span> <span class="st">"auto"</span>,</span>
<span>  transformations <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"mkin"</span>, <span class="st">"saemix"</span><span class="op">)</span>,</span>
<span>  degparms_start <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/numeric.html" class="external-link">numeric</a></span><span class="op">(</span><span class="op">)</span>,</span>
<span>  test_log_parms <span class="op">=</span> <span class="cn">FALSE</span>,</span>
<span>  conf.level <span class="op">=</span> <span class="fl">0.6</span>,</span>
<span>  verbose <span class="op">=</span> <span class="cn">FALSE</span>,</span>
<span>  <span class="va">...</span></span>
<span><span class="op">)</span></span>
<span></span>
<span><span class="fu">saemix_data</span><span class="op">(</span><span class="va">object</span>, verbose <span class="op">=</span> <span class="cn">FALSE</span>, <span class="va">...</span><span class="op">)</span></span>
<span></span>
<span><span class="co"># S3 method for saem.mmkin</span></span>
<span><span class="fu"><a href="parms.html">parms</a></span><span class="op">(</span><span class="va">object</span>, ci <span class="op">=</span> <span class="cn">FALSE</span>, <span class="va">...</span><span class="op">)</span></span></code></pre></div>
    </div>

    <div id="arguments">
    <h2>Arguments</h2>
    <dl><dt>object</dt>
<dd><p>An <a href="mmkin.html">mmkin</a> row object containing several fits of the same
<a href="mkinmod.html">mkinmod</a> model to different datasets</p></dd>


<dt>...</dt>
<dd><p>Further parameters passed to <a href="https://rdrr.io/pkg/saemix/man/saemixModel.html" class="external-link">saemix::saemixModel</a>.</p></dd>


<dt>transformations</dt>
<dd><p>Per default, all parameter transformations are done
in mkin. If this argument is set to 'saemix', parameter transformations
are done in 'saemix' for the supported cases, i.e. (as of version 1.1.2)
SFO, FOMC, DFOP and HS without fixing <code>parent_0</code>, and SFO or DFOP with
one SFO metabolite.</p></dd>


<dt>degparms_start</dt>
<dd><p>Parameter values given as a named numeric vector will
be used to override the starting values obtained from the 'mmkin' object.</p></dd>


<dt>test_log_parms</dt>
<dd><p>If TRUE, an attempt is made to use more robust starting
values for population parameters fitted as log parameters in mkin (like
rate constants) by only considering rate constants that pass the t-test
when calculating mean degradation parameters using <a href="mean_degparms.html">mean_degparms</a>.</p></dd>


<dt>conf.level</dt>
<dd><p>Possibility to adjust the required confidence level
for parameter that are tested if requested by 'test_log_parms'.</p></dd>


<dt>solution_type</dt>
<dd><p>Possibility to specify the solution type in case the
automatic choice is not desired</p></dd>


<dt>nbiter.saemix</dt>
<dd><p>Convenience option to increase the number of
iterations</p></dd>


<dt>control</dt>
<dd><p>Passed to <a href="https://rdrr.io/pkg/saemix/man/saemix.html" class="external-link">saemix::saemix</a>.</p></dd>


<dt>fail_with_errors</dt>
<dd><p>Should a failure to compute standard errors
from the inverse of the Fisher Information Matrix be a failure?</p></dd>


<dt>verbose</dt>
<dd><p>Should we print information about created objects of
type <a href="https://rdrr.io/pkg/saemix/man/SaemixModel-class.html" class="external-link">saemix::SaemixModel</a> and <a href="https://rdrr.io/pkg/saemix/man/SaemixData-class.html" class="external-link">saemix::SaemixData</a>?</p></dd>


<dt>quiet</dt>
<dd><p>Should we suppress the messages saemix prints at the beginning
and the end of the optimisation process?</p></dd>


<dt>x</dt>
<dd><p>An saem.mmkin object to print</p></dd>


<dt>digits</dt>
<dd><p>Number of digits to use for printing</p></dd>


<dt>ci</dt>
<dd><p>Should a matrix with estimates and confidence interval boundaries
be returned? If FALSE (default), a vector of estimates is returned.</p></dd>

</dl></div>
    <div id="value">
    <h2>Value</h2>
    

<p>An S3 object of class 'saem.mmkin', containing the fitted
<a href="https://rdrr.io/pkg/saemix/man/SaemixObject-class.html" class="external-link">saemix::SaemixObject</a> as a list component named 'so'. The
object also inherits from 'mixed.mmkin'.</p>


<p>An <a href="https://rdrr.io/pkg/saemix/man/SaemixModel-class.html" class="external-link">saemix::SaemixModel</a> object.</p>


<p>An <a href="https://rdrr.io/pkg/saemix/man/SaemixData-class.html" class="external-link">saemix::SaemixData</a> object.</p>
    </div>
    <div id="details">
    <h2>Details</h2>
    <p>An mmkin row object is essentially a list of mkinfit objects that have been
obtained by fitting the same model to a list of datasets using <a href="mkinfit.html">mkinfit</a>.</p>
<p>Starting values for the fixed effects (population mean parameters, argument
psi0 of <code><a href="https://rdrr.io/pkg/saemix/man/saemixModel.html" class="external-link">saemix::saemixModel()</a></code> are the mean values of the parameters found
using <a href="mmkin.html">mmkin</a>.</p>
    </div>
    <div id="see-also">
    <h2>See also</h2>
    <div class="dont-index"><p><a href="summary.saem.mmkin.html">summary.saem.mmkin</a> <a href="plot.mixed.mmkin.html">plot.mixed.mmkin</a></p></div>
    </div>

    <div id="ref-examples">
    <h2>Examples</h2>
    <div class="sourceCode"><pre class="sourceCode r"><code><span class="r-in"><span><span class="co"># \dontrun{</span></span></span>
<span class="r-in"><span><span class="va">ds</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">lapply</a></span><span class="op">(</span><span class="va">experimental_data_for_UBA_2019</span><span class="op">[</span><span class="fl">6</span><span class="op">:</span><span class="fl">10</span><span class="op">]</span>,</span></span>
<span class="r-in"><span> <span class="kw">function</span><span class="op">(</span><span class="va">x</span><span class="op">)</span> <span class="fu"><a href="https://rdrr.io/r/base/subset.html" class="external-link">subset</a></span><span class="op">(</span><span class="va">x</span><span class="op">$</span><span class="va">data</span><span class="op">[</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"name"</span>, <span class="st">"time"</span>, <span class="st">"value"</span><span class="op">)</span><span class="op">]</span><span class="op">)</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">ds</span><span class="op">)</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/base/paste.html" class="external-link">paste</a></span><span class="op">(</span><span class="st">"Dataset"</span>, <span class="fl">6</span><span class="op">:</span><span class="fl">10</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_mmkin_parent_p0_fixed</span> <span class="op">&lt;-</span> <span class="fu"><a href="mmkin.html">mmkin</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="va">ds</span>,</span></span>
<span class="r-in"><span>  state.ini <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fl">100</span><span class="op">)</span>, fixed_initials <span class="op">=</span> <span class="st">"parent"</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_p0_fixed</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin_parent_p0_fixed</span><span class="op">)</span></span></span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="va">f_mmkin_parent</span> <span class="op">&lt;-</span> <span class="fu"><a href="mmkin.html">mmkin</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"FOMC"</span>, <span class="st">"DFOP"</span><span class="op">)</span>, <span class="va">ds</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_sfo</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin_parent</span><span class="op">[</span><span class="st">"SFO"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_fomc</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin_parent</span><span class="op">[</span><span class="st">"FOMC"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_dfop</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin_parent</span><span class="op">[</span><span class="st">"DFOP"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="fu"><a href="illparms.html">illparms</a></span><span class="op">(</span><span class="va">f_saem_dfop</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> [1] "sd(g_qlogis)"</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/stats/update.html" class="external-link">update</a></span><span class="op">(</span><span class="va">f_saem_dfop</span>, covariance.model <span class="op">=</span> <span class="fu"><a href="https://rdrr.io/r/base/diag.html" class="external-link">diag</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="fl">1</span>, <span class="fl">1</span>, <span class="fl">1</span>, <span class="fl">0</span><span class="op">)</span><span class="op">)</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Kinetic nonlinear mixed-effects model fit by SAEM</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Structural model:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            * parent</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Data:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 90 observations of 1 variable(s) grouped in 5 datasets</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Likelihood computed by importance sampling</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>     AIC   BIC logLik</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   490.6 487.5 -237.3</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Fitted parameters:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>             estimate   lower   upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_0      93.902 91.3695 96.4339</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k1        -2.936 -3.9950 -1.8762</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k2        -3.091 -4.9290 -1.2523</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> g_qlogis      -0.366 -0.6484 -0.0836</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> a.1            2.385  2.0033  2.7664</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.parent_0    2.476  0.3890  4.5623</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k1      1.195  0.4381  1.9517</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k2      2.092  0.7906  3.3932</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/stats/AIC.html" class="external-link">AIC</a></span><span class="op">(</span><span class="va">f_saem_dfop</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> [1] 493.9811</span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="co"># The returned saem.mmkin object contains an SaemixObject, therefore we can use</span></span></span>
<span class="r-in"><span><span class="co"># functions from saemix</span></span></span>
<span class="r-in"><span><span class="kw"><a href="https://rdrr.io/r/base/library.html" class="external-link">library</a></span><span class="op">(</span><span class="va">saemix</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Loading required package: npde</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Package saemix, version 3.1</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span>   please direct bugs, questions and feedback to emmanuelle.comets@inserm.fr</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> </span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Attaching package: ‘saemix’</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> The following objects are masked from ‘package:npde’:</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> </span>
<span class="r-msg co"><span class="r-pr">#&gt;</span>     kurtosis, skewness</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/compare.saemix.html" class="external-link">compare.saemix</a></span><span class="op">(</span><span class="va">f_saem_sfo</span><span class="op">$</span><span class="va">so</span>, <span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, <span class="va">f_saem_dfop</span><span class="op">$</span><span class="va">so</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Likelihoods calculated by importance sampling</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>        AIC      BIC</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 1 624.2598 622.3070</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 2 467.8664 465.1324</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 3 493.9811 490.4660</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"convergence"</span><span class="op">)</span></span></span>
<span class="r-plt img"><img src="saem-1.png" alt="" width="700" height="433"></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"individual.fit"</span><span class="op">)</span></span></span>
<span class="r-plt img"><img src="saem-2.png" alt="" width="700" height="433"></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"npde"</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Simulating data using nsim = 1000 simulated datasets</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Computing WRES and npde .</span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Please use npdeSaemix to obtain VPC and npde</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, plot.type <span class="op">=</span> <span class="st">"vpc"</span><span class="op">)</span></span></span>
<span class="r-plt img"><img src="saem-3.png" alt="" width="700" height="433"></span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="va">f_mmkin_parent_tc</span> <span class="op">&lt;-</span> <span class="fu"><a href="https://rdrr.io/r/stats/update.html" class="external-link">update</a></span><span class="op">(</span><span class="va">f_mmkin_parent</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_fomc_tc</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin_parent_tc</span><span class="op">[</span><span class="st">"FOMC"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/compare.saemix.html" class="external-link">compare.saemix</a></span><span class="op">(</span><span class="va">f_saem_fomc</span><span class="op">$</span><span class="va">so</span>, <span class="va">f_saem_fomc_tc</span><span class="op">$</span><span class="va">so</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Likelihoods calculated by importance sampling</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>        AIC      BIC</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 1 467.8664 465.1324</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 2 469.8018 466.6773</span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="va">sfo_sfo</span> <span class="op">&lt;-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span>, <span class="st">"A1"</span><span class="op">)</span>,</span></span>
<span class="r-in"><span>  A1 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Temporary DLL for differentials generated and loaded</span>
<span class="r-in"><span><span class="va">fomc_sfo</span> <span class="op">&lt;-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"FOMC"</span>, <span class="st">"A1"</span><span class="op">)</span>,</span></span>
<span class="r-in"><span>  A1 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Temporary DLL for differentials generated and loaded</span>
<span class="r-in"><span><span class="va">dfop_sfo</span> <span class="op">&lt;-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span>parent <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"DFOP"</span>, <span class="st">"A1"</span><span class="op">)</span>,</span></span>
<span class="r-in"><span>  A1 <span class="op">=</span> <span class="fu"><a href="mkinmod.html">mkinsub</a></span><span class="op">(</span><span class="st">"SFO"</span><span class="op">)</span><span class="op">)</span></span></span>
<span class="r-msg co"><span class="r-pr">#&gt;</span> Temporary DLL for differentials generated and loaded</span>
<span class="r-in"><span><span class="co"># The following fit uses analytical solutions for SFO-SFO and DFOP-SFO,</span></span></span>
<span class="r-in"><span><span class="co"># and compiled ODEs for FOMC that are much slower</span></span></span>
<span class="r-in"><span><span class="va">f_mmkin</span> <span class="op">&lt;-</span> <span class="fu"><a href="mmkin.html">mmkin</a></span><span class="op">(</span><span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span></span></span>
<span class="r-in"><span>    <span class="st">"SFO-SFO"</span> <span class="op">=</span> <span class="va">sfo_sfo</span>, <span class="st">"FOMC-SFO"</span> <span class="op">=</span> <span class="va">fomc_sfo</span>, <span class="st">"DFOP-SFO"</span> <span class="op">=</span> <span class="va">dfop_sfo</span><span class="op">)</span>,</span></span>
<span class="r-in"><span>  <span class="va">ds</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="co"># saem fits of SFO-SFO and DFOP-SFO to these data take about five seconds</span></span></span>
<span class="r-in"><span><span class="co"># each on this system, as we use analytical solutions written for saemix.</span></span></span>
<span class="r-in"><span><span class="co"># When using the analytical solutions written for mkin this took around</span></span></span>
<span class="r-in"><span><span class="co"># four minutes</span></span></span>
<span class="r-in"><span><span class="va">f_saem_sfo_sfo</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin</span><span class="op">[</span><span class="st">"SFO-SFO"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="va">f_saem_dfop_sfo</span> <span class="op">&lt;-</span> <span class="fu">saem</span><span class="op">(</span><span class="va">f_mmkin</span><span class="op">[</span><span class="st">"DFOP-SFO"</span>, <span class="op">]</span><span class="op">)</span></span></span>
<span class="r-in"><span><span class="co"># We can use print, plot and summary methods to check the results</span></span></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/print.html" class="external-link">print</a></span><span class="op">(</span><span class="va">f_saem_dfop_sfo</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Kinetic nonlinear mixed-effects model fit by SAEM</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Structural model:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            * parent</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> d_A1/dt = + f_parent_to_A1 * ((k1 * g * exp(-k1 * time) + k2 * (1 - g)</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            exp(-k2 * time))) * parent - k_A1 * A1</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Data:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 170 observations of 2 variable(s) grouped in 5 datasets</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Likelihood computed by importance sampling</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   AIC   BIC logLik</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   842 836.9   -408</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Fitted parameters:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                    estimate   lower   upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_0            93.7701 91.1458 96.3945</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_A1            -5.8116 -7.5998 -4.0234</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> f_parent_qlogis     -0.9608 -1.3654 -0.5562</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k1              -2.5841 -3.6876 -1.4805</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k2              -3.5228 -5.3254 -1.7203</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> g_qlogis            -0.1027 -0.8719  0.6665</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> a.1                  1.8856  1.6676  2.1037</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.parent_0          2.7682  0.7668  4.7695</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_A1          1.7447  0.4047  3.0848</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.f_parent_qlogis   0.4525  0.1620  0.7431</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k1            1.2423  0.4560  2.0285</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k2            2.0390  0.7601  3.3180</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.g_qlogis          0.4439 -0.3069  1.1947</span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/r/base/plot.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_saem_dfop_sfo</span><span class="op">)</span></span></span>
<span class="r-plt img"><img src="saem-4.png" alt="" width="700" height="433"></span>
<span class="r-in"><span><span class="fu"><a href="https://rdrr.io/pkg/saemix/man/summary-methods.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_saem_dfop_sfo</span>, data <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span></span>
<span class="r-out co"><span class="r-pr">#&gt;</span> saemix version used for fitting:      3.1 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> mkin version used for pre-fitting:  1.1.2 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> R version used for fitting:         4.2.1 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Date of fit:     Fri Sep 16 10:30:47 2022 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Date of summary: Fri Sep 16 10:30:47 2022 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Equations:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            time)) / (g * exp(-k1 * time) + (1 - g) * exp(-k2 * time)))</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            * parent</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> d_A1/dt = + f_parent_to_A1 * ((k1 * g * exp(-k1 * time) + k2 * (1 - g)</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            * exp(-k2 * time)) / (g * exp(-k1 * time) + (1 - g) *</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>            exp(-k2 * time))) * parent - k_A1 * A1</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Data:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> 170 observations of 2 variable(s) grouped in 5 datasets</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Model predictions using solution type analytical </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Fitted in 9.651 s</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Using 300, 100 iterations and 10 chains</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Variance model: Constant variance </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Mean of starting values for individual parameters:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>        parent_0        log_k_A1 f_parent_qlogis          log_k1          log_k2 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span>         93.8102         -5.3734         -0.9711         -1.8799         -4.2708 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span>        g_qlogis </span>
<span class="r-out co"><span class="r-pr">#&gt;</span>          0.1356 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Fixed degradation parameter values:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> None</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Results:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Likelihood computed by importance sampling</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   AIC   BIC logLik</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   842 836.9   -408</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Optimised parameters:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                    est.   lower   upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_0        93.7701 91.1458 96.3945</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_A1        -5.8116 -7.5998 -4.0234</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> f_parent_qlogis -0.9608 -1.3654 -0.5562</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k1          -2.5841 -3.6876 -1.4805</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k2          -3.5228 -5.3254 -1.7203</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> g_qlogis        -0.1027 -0.8719  0.6665</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Correlation: </span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                 parnt_0 lg_k_A1 f_prnt_ log_k1  log_k2 </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k_A1        -0.0160                                </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> f_parent_qlogis -0.0263  0.0612                        </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k1           0.0100 -0.0014 -0.0033                </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> log_k2           0.0131  0.0050 -0.0011  0.0071        </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> g_qlogis        -0.0419 -0.0199  0.0026 -0.0765 -0.0707</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Random effects:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                      est.   lower  upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.parent_0        2.7682  0.7668 4.7695</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k_A1        1.7447  0.4047 3.0848</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.f_parent_qlogis 0.4525  0.1620 0.7431</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k1          1.2423  0.4560 2.0285</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.log_k2          2.0390  0.7601 3.3180</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> SD.g_qlogis        0.4439 -0.3069 1.1947</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Variance model:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>      est. lower upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> a.1 1.886 1.668 2.104</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Backtransformed parameters:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                     est.     lower    upper</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_0       93.770115 9.115e+01 96.39447</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> k_A1            0.002993 5.005e-04  0.01789</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> f_parent_to_A1  0.276720 2.034e-01  0.36443</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> k1              0.075467 2.503e-02  0.22753</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> k2              0.029516 4.867e-03  0.17902</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> g               0.474353 2.949e-01  0.66073</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Resulting formation fractions:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>                 ff</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_A1   0.2767</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent_sink 0.7233</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Estimated disappearance times:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>          DT50   DT90 DT50back DT50_k1 DT50_k2</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> parent  14.56  58.26    17.54   9.185   23.48</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> A1     231.62 769.41       NA      NA      NA</span>
<span class="r-out co"><span class="r-pr">#&gt;</span> </span>
<span class="r-out co"><span class="r-pr">#&gt;</span> Data:</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>          ds   name time observed predicted residual   std standardized</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    0     97.2  95.78623  1.41377 1.886     0.749758</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    0     96.4  95.78623  0.61377 1.886     0.325498</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    3     71.1  71.34666 -0.24666 1.886    -0.130812</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    3     69.2  71.34666 -2.14666 1.886    -1.138429</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    6     58.1  56.49768  1.60232 1.886     0.849749</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent    6     56.6  56.49768  0.10232 1.886     0.054262</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   10     44.4  44.53511 -0.13511 1.886    -0.071650</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   10     43.4  44.53511 -1.13511 1.886    -0.601974</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   20     33.3  29.77451  3.52549 1.886     1.869656</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   20     29.2  29.77451 -0.57451 1.886    -0.304675</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   34     17.6  19.32540 -1.72540 1.886    -0.915023</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   34     18.0  19.32540 -1.32540 1.886    -0.702894</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   55     10.5  10.42781  0.07219 1.886     0.038282</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   55      9.3  10.42781 -1.12781 1.886    -0.598107</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   90      4.5   3.74190  0.75810 1.886     0.402037</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent   90      4.7   3.74190  0.95810 1.886     0.508102</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent  112      3.0   1.96485  1.03515 1.886     0.548966</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent  112      3.4   1.96485  1.43515 1.886     0.761096</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent  132      2.3   1.09395  1.20605 1.886     0.639596</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6 parent  132      2.7   1.09395  1.60605 1.886     0.851726</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1    3      4.3   4.72702 -0.42702 1.886    -0.226458</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1    3      4.6   4.72702 -0.12702 1.886    -0.067361</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1    6      7.0   7.51314 -0.51314 1.886    -0.272128</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1    6      7.2   7.51314 -0.31314 1.886    -0.166063</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   10      8.2   9.63719 -1.43719 1.886    -0.762179</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   10      8.0   9.63719 -1.63719 1.886    -0.868244</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   20     11.0  11.84931 -0.84931 1.886    -0.450409</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   20     13.7  11.84931  1.85069 1.886     0.981468</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   34     11.5  12.82336 -1.32336 1.886    -0.701808</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   34     12.7  12.82336 -0.12336 1.886    -0.065418</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   55     14.9  12.89456  2.00544 1.886     1.063533</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   55     14.5  12.89456  1.60544 1.886     0.851403</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   90     12.1  11.55919  0.54081 1.886     0.286806</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1   90     12.3  11.55919  0.74081 1.886     0.392871</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1  112      9.9  10.42334 -0.52334 1.886    -0.277539</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1  112     10.2  10.42334 -0.22334 1.886    -0.118442</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1  132      8.8   9.37987 -0.57987 1.886    -0.307519</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 6     A1  132      7.8   9.37987 -1.57987 1.886    -0.837844</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    0     93.6  90.95702  2.64298 1.886     1.401639</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    0     92.3  90.95702  1.34298 1.886     0.712217</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    3     87.0  84.77506  2.22494 1.886     1.179942</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    3     82.2  84.77506 -2.57506 1.886    -1.365616</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    7     74.0  77.60962 -3.60962 1.886    -1.914268</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent    7     73.9  77.60962 -3.70962 1.886    -1.967301</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   14     64.2  67.50646 -3.30646 1.886    -1.753499</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   14     69.5  67.50646  1.99354 1.886     1.057221</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   30     54.0  52.48909  1.51091 1.886     0.801271</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   30     54.6  52.48909  2.11091 1.886     1.119465</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   60     41.1  39.54372  1.55628 1.886     0.825335</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   60     38.4  39.54372 -1.14372 1.886    -0.606542</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   90     32.5  33.87968 -1.37968 1.886    -0.731676</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent   90     35.5  33.87968  1.62032 1.886     0.859298</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent  120     28.1  30.41071 -2.31071 1.886    -1.225427</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent  120     29.0  30.41071 -1.41071 1.886    -0.748135</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent  180     26.5  25.36386  1.13614 1.886     0.602524</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7 parent  180     27.6  25.36386  2.23614 1.886     1.185881</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1    3      3.9   2.74863  1.15137 1.886     0.610600</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1    3      3.1   2.74863  0.35137 1.886     0.186341</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1    7      6.9   5.92686  0.97314 1.886     0.516081</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1    7      6.6   5.92686  0.67314 1.886     0.356983</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   14     10.4  10.38800  0.01200 1.886     0.006362</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   14      8.3  10.38800 -2.08800 1.886    -1.107320</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   30     14.4  16.93529 -2.53529 1.886    -1.344524</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   30     13.7  16.93529 -3.23529 1.886    -1.715751</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   60     22.1  22.33044 -0.23044 1.886    -0.122209</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   60     22.3  22.33044 -0.03044 1.886    -0.016144</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   90     27.5  24.42300  3.07700 1.886     1.631809</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1   90     25.4  24.42300  0.97700 1.886     0.518127</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1  120     28.0  25.51140  2.48860 1.886     1.319768</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1  120     26.6  25.51140  1.08860 1.886     0.577313</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1  180     25.8  26.80282 -1.00282 1.886    -0.531818</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 7     A1  180     25.3  26.80282 -1.50282 1.886    -0.796981</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    0     91.9  91.08733  0.81267 1.886     0.430980</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    0     90.8  91.08733 -0.28733 1.886    -0.152377</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    1     64.9  67.55332 -2.65332 1.886    -1.407123</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    1     66.2  67.55332 -1.35332 1.886    -0.717701</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    3     43.5  41.65811  1.84189 1.886     0.976800</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    3     44.1  41.65811  2.44189 1.886     1.294994</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    8     18.3  19.65773 -1.35773 1.886    -0.720038</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent    8     18.1  19.65773 -1.55773 1.886    -0.826103</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   14     10.2  10.65118 -0.45118 1.886    -0.239269</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   14     10.8  10.65118  0.14882 1.886     0.078925</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   27      4.9   3.11694  1.78306 1.886     0.945601</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   27      3.3   3.11694  0.18306 1.886     0.097082</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   48      1.6   0.43165  1.16835 1.886     0.619603</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   48      1.5   0.43165  1.06835 1.886     0.566570</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   70      1.1   0.05441  1.04559 1.886     0.554503</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8 parent   70      0.9   0.05441  0.84559 1.886     0.448438</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    1      9.6   7.66431  1.93569 1.886     1.026546</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    1      7.7   7.66431  0.03569 1.886     0.018930</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    3     15.0  15.57948 -0.57948 1.886    -0.307311</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    3     15.1  15.57948 -0.47948 1.886    -0.254279</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    8     21.2  20.38988  0.81012 1.886     0.429625</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1    8     21.1  20.38988  0.71012 1.886     0.376593</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   14     19.7  20.16439 -0.46439 1.886    -0.246276</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   14     18.9  20.16439 -1.26439 1.886    -0.670535</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   27     17.5  16.40918  1.09082 1.886     0.578489</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   27     15.9  16.40918 -0.50918 1.886    -0.270030</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   48      9.5  10.12011 -0.62011 1.886    -0.328861</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   48      9.8  10.12011 -0.32011 1.886    -0.169764</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   70      6.2   5.79080  0.40920 1.886     0.217011</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 8     A1   70      6.1   5.79080  0.30920 1.886     0.163979</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    0     99.8  97.38786  2.41214 1.886     1.279218</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    0     98.3  97.38786  0.91214 1.886     0.483731</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    1     77.1  79.25431 -2.15431 1.886    -1.142481</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    1     77.2  79.25431 -2.05431 1.886    -1.089449</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    3     59.0  55.69866  3.30134 1.886     1.750781</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    3     58.1  55.69866  2.40134 1.886     1.273489</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    8     27.4  31.64893 -4.24893 1.886    -2.253314</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent    8     29.2  31.64893 -2.44893 1.886    -1.298729</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   14     19.1  22.57316 -3.47316 1.886    -1.841901</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   14     29.6  22.57316  7.02684 1.886     3.726507</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   27     10.1  14.11345 -4.01345 1.886    -2.128430</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   27     18.2  14.11345  4.08655 1.886     2.167199</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   48      4.5   6.95586 -2.45586 1.886    -1.302400</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   48      9.1   6.95586  2.14414 1.886     1.137093</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   70      2.3   3.31753 -1.01753 1.886    -0.539619</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   70      2.9   3.31753 -0.41753 1.886    -0.221424</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   91      2.0   1.63642  0.36358 1.886     0.192816</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent   91      1.8   1.63642  0.16358 1.886     0.086751</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent  120      2.0   0.61667  1.38333 1.886     0.733614</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9 parent  120      2.2   0.61667  1.58333 1.886     0.839679</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    1      4.2   3.67247  0.52753 1.886     0.279763</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    1      3.9   3.67247  0.22753 1.886     0.120666</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    3      7.4   8.36240 -0.96240 1.886    -0.510385</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    3      7.9   8.36240 -0.46240 1.886    -0.245223</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    8     14.5  12.80590  1.69410 1.886     0.898422</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1    8     13.7  12.80590  0.89410 1.886     0.474162</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   14     14.2  13.99625  0.20375 1.886     0.108053</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   14     12.2  13.99625 -1.79625 1.886    -0.952596</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   27     13.7  14.22730 -0.52730 1.886    -0.279641</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   27     13.2  14.22730 -1.02730 1.886    -0.544803</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   48     13.6  13.33713  0.26287 1.886     0.139406</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   48     15.4  13.33713  2.06287 1.886     1.093991</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   70     10.4  11.84008 -1.44008 1.886    -0.763708</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   70     11.6  11.84008 -0.24008 1.886    -0.127318</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   91     10.0  10.30732 -0.30732 1.886    -0.162980</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1   91      9.5  10.30732 -0.80732 1.886    -0.428142</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1  120      9.1   8.33981  0.76019 1.886     0.403149</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>   Dataset 9     A1  120      9.0   8.33981  0.66019 1.886     0.350117</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent    0     96.1  93.70349  2.39651 1.886     1.270926</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent    0     94.3  93.70349  0.59651 1.886     0.316342</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent    8     73.9  77.86253 -3.96253 1.886    -2.101429</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent    8     73.9  77.86253 -3.96253 1.886    -2.101429</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   14     69.4  70.18665 -0.78665 1.886    -0.417182</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   14     73.1  70.18665  2.91335 1.886     1.545019</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   21     65.6  64.03245  1.56755 1.886     0.831308</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   21     65.3  64.03245  1.26755 1.886     0.672210</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   41     55.9  54.71491  1.18509 1.886     0.628480</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   41     54.4  54.71491 -0.31491 1.886    -0.167007</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   63     47.0  49.63436 -2.63436 1.886    -1.397065</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   63     49.3  49.63436 -0.33436 1.886    -0.177319</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   91     44.7  45.08853 -0.38853 1.886    -0.206049</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent   91     46.7  45.08853  1.61147 1.886     0.854600</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent  120     42.1  41.07653  1.02347 1.886     0.542772</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10 parent  120     41.3  41.07653  0.22347 1.886     0.118513</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1    8      3.3   4.08295 -0.78295 1.886    -0.415218</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1    8      3.4   4.08295 -0.68295 1.886    -0.362186</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   14      3.9   6.04367 -2.14367 1.886    -1.136841</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   14      2.9   6.04367 -3.14367 1.886    -1.667165</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   21      6.4   7.59693 -1.19693 1.886    -0.634761</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   21      7.2   7.59693 -0.39693 1.886    -0.210502</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   41      9.1   9.86436 -0.76436 1.886    -0.405361</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   41      8.5   9.86436 -1.36436 1.886    -0.723555</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   63     11.7  10.99397  0.70603 1.886     0.374425</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   63     12.0  10.99397  1.00603 1.886     0.533522</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   91     13.3  11.91274  1.38726 1.886     0.735696</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1   91     13.2  11.91274  1.28726 1.886     0.682663</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1  120     14.3  12.66519  1.63481 1.886     0.866981</span>
<span class="r-out co"><span class="r-pr">#&gt;</span>  Dataset 10     A1  120     12.1  12.66519 -0.56519 1.886    -0.299733</span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="co"># The following takes about 6 minutes</span></span></span>
<span class="r-in"><span><span class="co">#f_saem_dfop_sfo_deSolve &lt;- saem(f_mmkin["DFOP-SFO", ], solution_type = "deSolve",</span></span></span>
<span class="r-in"><span><span class="co">#  control = list(nbiter.saemix = c(200, 80), nbdisplay = 10))</span></span></span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="co">#saemix::compare.saemix(list(</span></span></span>
<span class="r-in"><span><span class="co">#  f_saem_dfop_sfo$so,</span></span></span>
<span class="r-in"><span><span class="co">#  f_saem_dfop_sfo_deSolve$so))</span></span></span>
<span class="r-in"><span></span></span>
<span class="r-in"><span><span class="co"># If the model supports it, we can also use eigenvalue based solutions, which</span></span></span>
<span class="r-in"><span><span class="co"># take a similar amount of time</span></span></span>
<span class="r-in"><span><span class="co">#f_saem_sfo_sfo_eigen &lt;- saem(f_mmkin["SFO-SFO", ], solution_type = "eigen",</span></span></span>
<span class="r-in"><span><span class="co">#  control = list(nbiter.saemix = c(200, 80), nbdisplay = 10))</span></span></span>
<span class="r-in"><span><span class="co"># }</span></span></span>
</code></pre></div>
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