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diff --git a/docs/dev/reference/dimethenamid_2018.html b/docs/dev/reference/dimethenamid_2018.html index 60c15ade..5fb94988 100644 --- a/docs/dev/reference/dimethenamid_2018.html +++ b/docs/dev/reference/dimethenamid_2018.html @@ -1,72 +1,17 @@ -<!-- Generated by pkgdown: do not edit by hand --> <!DOCTYPE html> -<html lang="en"> - <head> - <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>Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018 • 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="Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018" /> -<meta property="og:description" content="The datasets were extracted from the active substance evaluation dossier +<!-- 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>Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018 • 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="Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018 — dimethenamid_2018"><meta property="og:description" content="The datasets were extracted from the active substance evaluation dossier published by EFSA. Kinetic evaluations shown for these datasets are intended to illustrate and advance kinetic modelling. The fact that these data and some results are shown here does not imply a license to use them in the context of pesticide registrations, as the use of the data may be -constrained by data protection regulations." /> - - -<meta name="robots" content="noindex"> - -<!-- mathjax --> -<script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/MathJax.js" integrity="sha256-nvJJv9wWKEm88qvoQl9ekL2J+k/RWIsaSScxxlsrv8k=" crossorigin="anonymous"></script> -<script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/config/TeX-AMS-MML_HTMLorMML.js" integrity="sha256-84DKXVJXs0/F8OTMzX4UR909+jtl4G7SPypPavF+GfA=" crossorigin="anonymous"></script> - -<!--[if lt IE 9]> +constrained by data protection regulations."><meta name="robots" content="noindex"><!-- mathjax --><script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/MathJax.js" integrity="sha256-nvJJv9wWKEm88qvoQl9ekL2J+k/RWIsaSScxxlsrv8k=" crossorigin="anonymous"></script><script src="https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.5/config/TeX-AMS-MML_HTMLorMML.js" integrity="sha256-84DKXVJXs0/F8OTMzX4UR909+jtl4G7SPypPavF+GfA=" crossorigin="anonymous"></script><!--[if lt IE 9]> <script src="https://oss.maxcdn.com/html5shiv/3.7.3/html5shiv.min.js"></script> <script src="https://oss.maxcdn.com/respond/1.4.2/respond.min.js"></script> -<![endif]--> +<![endif]--></head><body data-spy="scroll" data-target="#toc"> + - - - </head> - - <body data-spy="scroll" data-target="#toc"> <div class="container template-reference-topic"> - <header> - <div class="navbar navbar-default navbar-fixed-top" role="navigation"> + <header><div class="navbar navbar-default navbar-fixed-top" role="navigation"> <div class="container"> <div class="navbar-header"> <button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#navbar" aria-expanded="false"> @@ -82,8 +27,7 @@ constrained by data protection regulations." /> </div> <div id="navbar" class="navbar-collapse collapse"> - <ul class="nav navbar-nav"> - <li> + <ul class="nav navbar-nav"><li> <a href="../reference/index.html">Functions and data</a> </li> <li class="dropdown"> @@ -92,8 +36,7 @@ constrained by data protection regulations." /> <span class="caret"></span> </a> - <ul class="dropdown-menu" role="menu"> - <li> + <ul class="dropdown-menu" role="menu"><li> <a href="../articles/mkin.html">Introduction to mkin</a> </li> <li> @@ -117,34 +60,27 @@ constrained by data protection regulations." /> <li> <a href="../articles/web_only/benchmarks.html">Some benchmark timings</a> </li> - </ul> -</li> + </ul></li> <li> <a href="../news/index.html">News</a> </li> - </ul> - <ul class="nav navbar-nav navbar-right"> - <li> - <a href="https://github.com/jranke/mkin/"> + </ul><ul class="nav navbar-nav navbar-right"><li> + <a href="https://github.com/jranke/mkin/" class="external-link"> <span class="fab fa-github fa-lg"></span> </a> </li> - </ul> - - </div><!--/.nav-collapse --> + </ul></div><!--/.nav-collapse --> </div><!--/.container --> </div><!--/.navbar --> - </header> - -<div class="row"> + </header><div class="row"> <div class="col-md-9 contents"> <div class="page-header"> <h1>Aerobic soil degradation data on dimethenamid and dimethenamid-P from the EU assessment in 2018</h1> - <small class="dont-index">Source: <a href='https://github.com/jranke/mkin/blob/master/R/dimethenamid_2018.R'><code>R/dimethenamid_2018.R</code></a></small> + <small class="dont-index">Source: <a href="https://github.com/jranke/mkin/blob/HEAD/R/dimethenamid_2018.R" class="external-link"><code>R/dimethenamid_2018.R</code></a></small> <div class="hidden name"><code>dimethenamid_2018.Rd</code></div> </div> @@ -157,294 +93,368 @@ context of pesticide registrations, as the use of the data may be constrained by data protection regulations.</p> </div> - <pre class="usage"><span class='va'>dimethenamid_2018</span></pre> - - - <h2 class="hasAnchor" id="format"><a class="anchor" href="#format"></a>Format</h2> - - <p>An <a href='mkindsg.html'>mkindsg</a> object grouping seven datasets with some meta information</p> - <h2 class="hasAnchor" id="source"><a class="anchor" href="#source"></a>Source</h2> + <div id="ref-usage"> + <div class="sourceCode"><pre class="sourceCode r"><code><span class="va">dimethenamid_2018</span></code></pre></div> + </div> + <div id="format"> + <h2>Format</h2> + <p>An <a href="mkindsg.html">mkindsg</a> object grouping seven datasets with some meta information</p> + </div> + <div id="source"> + <h2>Source</h2> <p>Rapporteur Member State Germany, Co-Rapporteur Member State Bulgaria (2018) Renewal Assessment Report Dimethenamid-P Volume 3 - B.8 Environmental fate and behaviour Rev. 2 - November 2017 -<a href='https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716'>https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716</a></p> - <h2 class="hasAnchor" id="details"><a class="anchor" href="#details"></a>Details</h2> - +<a href="https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716" class="external-link">https://open.efsa.europa.eu/study-inventory/EFSA-Q-2014-00716</a></p> + </div> + <div id="details"> + <h2>Details</h2> <p>The R code used to create this data object is installed with this package in the 'dataset_generation' directory. In the code, page numbers are given for specific pieces of information in the comments.</p> + </div> - <h2 class="hasAnchor" id="examples"><a class="anchor" href="#examples"></a>Examples</h2> - <pre class="examples"><div class='input'><span class='fu'><a href='https://rdrr.io/r/base/print.html'>print</a></span><span class='op'>(</span><span class='va'>dimethenamid_2018</span><span class='op'>)</span> -</div><div class='output co'>#> <mkindsg> holding 7 mkinds objects -#> Title $title: Aerobic soil degradation data on dimethenamid-P from the EU assessment in 2018 -#> Occurrence of observed compounds $observed_n: -#> DMTAP M23 M27 M31 DMTA -#> 3 7 7 7 4 -#> Time normalisation factors $f_time_norm: -#> [1] 1.0000000 0.9706477 1.2284784 1.2284784 0.6233856 0.7678922 0.6733938 -#> Meta information $meta: -#> study usda_soil_type study_moisture_ref_type rel_moisture -#> Calke Unsworth 2014 Sandy loam pF2 1.00 -#> Borstel Staudenmaier 2009 Sand pF1 0.50 -#> Elliot 1 Wendt 1997 Clay loam pF2.5 0.75 -#> Elliot 2 Wendt 1997 Clay loam pF2.5 0.75 -#> Flaach König 1996 Sandy clay loam pF1 0.40 -#> BBA 2.2 König 1995 Loamy sand pF1 0.40 -#> BBA 2.3 König 1995 Sandy loam pF1 0.40 -#> study_ref_moisture temperature -#> Calke NA 20 -#> Borstel 23.00 20 -#> Elliot 1 33.37 23 -#> Elliot 2 33.37 23 -#> Flaach NA 20 -#> BBA 2.2 NA 20 -#> BBA 2.3 NA 20</div><div class='input'><span class='va'>dmta_ds</span> <span class='op'><-</span> <span class='fu'><a href='https://rdrr.io/r/base/lapply.html'>lapply</a></span><span class='op'>(</span><span class='fl'>1</span><span class='op'>:</span><span class='fl'>7</span>, <span class='kw'>function</span><span class='op'>(</span><span class='va'>i</span><span class='op'>)</span> <span class='op'>{</span> - <span class='va'>ds_i</span> <span class='op'><-</span> <span class='va'>dimethenamid_2018</span><span class='op'>$</span><span class='va'>ds</span><span class='op'>[[</span><span class='va'>i</span><span class='op'>]</span><span class='op'>]</span><span class='op'>$</span><span class='va'>data</span> - <span class='va'>ds_i</span><span class='op'>[</span><span class='va'>ds_i</span><span class='op'>$</span><span class='va'>name</span> <span class='op'>==</span> <span class='st'>"DMTAP"</span>, <span class='st'>"name"</span><span class='op'>]</span> <span class='op'><-</span> <span class='st'>"DMTA"</span> - <span class='va'>ds_i</span><span class='op'>$</span><span class='va'>time</span> <span class='op'><-</span> <span class='va'>ds_i</span><span class='op'>$</span><span class='va'>time</span> <span class='op'>*</span> <span class='va'>dimethenamid_2018</span><span class='op'>$</span><span class='va'>f_time_norm</span><span class='op'>[</span><span class='va'>i</span><span class='op'>]</span> - <span class='va'>ds_i</span> -<span class='op'>}</span><span class='op'>)</span> -<span class='fu'><a href='https://rdrr.io/r/base/names.html'>names</a></span><span class='op'>(</span><span class='va'>dmta_ds</span><span class='op'>)</span> <span class='op'><-</span> <span class='fu'><a href='https://rdrr.io/r/base/lapply.html'>sapply</a></span><span class='op'>(</span><span class='va'>dimethenamid_2018</span><span class='op'>$</span><span class='va'>ds</span>, <span class='kw'>function</span><span class='op'>(</span><span class='va'>ds</span><span class='op'>)</span> <span class='va'>ds</span><span class='op'>$</span><span class='va'>title</span><span class='op'>)</span> -<span class='va'>dmta_ds</span><span class='op'>[[</span><span class='st'>"Elliot"</span><span class='op'>]</span><span class='op'>]</span> <span class='op'><-</span> <span class='fu'><a href='https://rdrr.io/r/base/cbind.html'>rbind</a></span><span class='op'>(</span><span class='va'>dmta_ds</span><span class='op'>[[</span><span class='st'>"Elliot 1"</span><span class='op'>]</span><span class='op'>]</span>, <span class='va'>dmta_ds</span><span class='op'>[[</span><span class='st'>"Elliot 2"</span><span class='op'>]</span><span class='op'>]</span><span class='op'>)</span> -<span class='va'>dmta_ds</span><span class='op'>[[</span><span class='st'>"Elliot 1"</span><span class='op'>]</span><span class='op'>]</span> <span class='op'><-</span> <span class='cn'>NULL</span> -<span class='va'>dmta_ds</span><span class='op'>[[</span><span class='st'>"Elliot 2"</span><span class='op'>]</span><span class='op'>]</span> <span class='op'><-</span> <span class='cn'>NULL</span> -<span class='co'># \dontrun{</span> -<span class='va'>dfop_sfo3_plus</span> <span class='op'><-</span> <span class='fu'><a href='mkinmod.html'>mkinmod</a></span><span class='op'>(</span> - DMTA <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='fu'><a href='https://rdrr.io/r/base/c.html'>c</a></span><span class='op'>(</span><span class='st'>"M23"</span>, <span class='st'>"M27"</span>, <span class='st'>"M31"</span><span class='op'>)</span><span class='op'>)</span>, - M23 <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>, - M27 <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>, - M31 <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'>"M27"</span>, sink <span class='op'>=</span> <span class='cn'>FALSE</span><span class='op'>)</span>, - quiet <span class='op'>=</span> <span class='cn'>TRUE</span> -<span class='op'>)</span> -<span class='va'>f_dmta_mkin_tc</span> <span class='op'><-</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'>list</a></span><span class='op'>(</span><span class='st'>"DFOP-SFO3+"</span> <span class='op'>=</span> <span class='va'>dfop_sfo3_plus</span><span class='op'>)</span>, - <span class='va'>dmta_ds</span>, quiet <span class='op'>=</span> <span class='cn'>TRUE</span>, error_model <span class='op'>=</span> <span class='st'>"tc"</span><span class='op'>)</span> -<span class='fu'><a href='nlmixr.mmkin.html'>nlmixr_model</a></span><span class='op'>(</span><span class='va'>f_dmta_mkin_tc</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='message'>With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span></div><div class='output co'>#> <span class='warning'>Warning: number of items to replace is not a multiple of replacement length</span></div><div class='output co'>#> function () -#> { -#> ini({ -#> DMTA_0 = 98.7132391714013 -#> eta.DMTA_0 ~ 2.32692496033921 -#> log_k_M23 = -3.92162409637283 -#> eta.log_k_M23 ~ 0.549278519419884 -#> log_k_M27 = -4.33057580082049 -#> eta.log_k_M27 ~ 0.855184233768426 -#> log_k_M31 = -4.24415516780733 -#> eta.log_k_M31 ~ 0.745746058085877 -#> log_k1 = -2.23515804885306 -#> eta.log_k1 ~ 0.901033446532357 -#> log_k2 = -3.77581484944379 -#> eta.log_k2 ~ 1.57682329638124 -#> g_qlogis = 0.436302910942805 -#> eta.g_qlogis ~ 3.10190528862808 -#> f_DMTA_tffm0_1_qlogis = -2.0914852208395 -#> eta.f_DMTA_tffm0_1_qlogis ~ 0.3 -#> f_DMTA_tffm0_2_qlogis = -2.17879574608926 -#> eta.f_DMTA_tffm0_2_qlogis ~ 0.3 -#> f_DMTA_tffm0_3_qlogis = -2.14036526460782 -#> eta.f_DMTA_tffm0_3_qlogis ~ 0.3 -#> sigma_low_DMTA = 0.700117227383809 -#> rsd_high_DMTA = 0.0257724286053519 -#> sigma_low_M23 = 0.700117227383809 -#> rsd_high_M23 = 0.0257724286053519 -#> sigma_low_M27 = 0.700117227383809 -#> rsd_high_M27 = 0.0257724286053519 -#> sigma_low_M31 = 0.700117227383809 -#> rsd_high_M31 = 0.0257724286053519 -#> }) -#> model({ -#> DMTA_0_model = DMTA_0 + eta.DMTA_0 -#> DMTA(0) = DMTA_0_model -#> k_M23 = exp(log_k_M23 + eta.log_k_M23) -#> k_M27 = exp(log_k_M27 + eta.log_k_M27) -#> k_M31 = exp(log_k_M31 + eta.log_k_M31) -#> k1 = exp(log_k1 + eta.log_k1) -#> k2 = exp(log_k2 + eta.log_k2) -#> g = expit(g_qlogis + eta.g_qlogis) -#> f_DMTA_to_M23 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis) -#> f_DMTA_to_M23 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis) -#> f_DMTA_to_M23 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis) -#> f_DMTA_to_M23 = f_DMTA_tffm0_1 -#> f_DMTA_to_M27 = f_DMTA_tffm0_2 * (1 - f_DMTA_tffm0_1) -#> f_DMTA_to_M31 = f_DMTA_tffm0_3 * (1 - f_DMTA_tffm0_2) * -#> (1 - f_DMTA_tffm0_1) -#> d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 - -#> g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 - -#> g) * exp(-k2 * time))) * DMTA -#> d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) + -#> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + -#> (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23 -#> d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) + -#> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + -#> (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 + -#> k_M31 * M31 -#> d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) + -#> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + -#> (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31 -#> DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA) -#> M23 ~ add(sigma_low_M23) + prop(rsd_high_M23) -#> M27 ~ add(sigma_low_M27) + prop(rsd_high_M27) -#> M31 ~ add(sigma_low_M31) + prop(rsd_high_M31) -#> }) -#> } -#> <environment: 0x555559d89920></div><div class='input'><span class='co'># The focei fit takes about four minutes on my system</span> -<span class='fu'><a href='https://rdrr.io/r/base/system.time.html'>system.time</a></span><span class='op'>(</span> - <span class='va'>f_dmta_nlmixr_focei</span> <span class='op'><-</span> <span class='fu'><a href='https://rdrr.io/pkg/nlmixr/man/nlmixr.html'>nlmixr</a></span><span class='op'>(</span><span class='va'>f_dmta_mkin_tc</span>, est <span class='op'>=</span> <span class='st'>"focei"</span>, - control <span class='op'>=</span> <span class='fu'>nlmixr</span><span class='fu'>::</span><span class='fu'><a href='https://rdrr.io/pkg/nlmixr/man/foceiControl.html'>foceiControl</a></span><span class='op'>(</span>print <span class='op'>=</span> <span class='fl'>500</span><span class='op'>)</span><span class='op'>)</span> -<span class='op'>)</span> -</div><div class='output co'>#> <span class='warning'>Warning: number of items to replace is not a multiple of replacement length</span></div><div class='output co'>#> <span class='message'><span style='color: #00BBBB;'>ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span></div><div class='output co'>#> <span class='message'><span style='color: #00BBBB;'>ℹ</span> Need to run with the source intact to parse comments</span></div><div class='output co'>#> <span class='message'>→ creating full model...</span></div><div class='output co'>#> <span class='message'>→ pruning branches (<span style='color: #262626; background-color: #DADADA;'>`if`</span>/<span style='color: #262626; background-color: #DADADA;'>`else`</span>)...</span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ loading into <span style='color: #0000BB;'>symengine</span> environment...</span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ creating full model...</span></div><div class='output co'>#> <span class='message'>→ pruning branches (<span style='color: #262626; background-color: #DADADA;'>`if`</span>/<span style='color: #262626; background-color: #DADADA;'>`else`</span>)...</span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ loading into <span style='color: #0000BB;'>symengine</span> environment...</span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ calculate jacobian</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:02 -#> </div><div class='output co'>#> <span class='message'>→ calculate sensitivities</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:04 -#> </div><div class='output co'>#> <span class='message'>→ calculate ∂(f)/∂(η)</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:01 -#> </div><div class='output co'>#> <span class='message'>→ calculate ∂(R²)/∂(η)</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:09 -#> </div><div class='output co'>#> <span class='message'>→ finding duplicate expressions in inner model...</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:07 -#> </div><div class='output co'>#> <span class='message'>→ optimizing duplicate expressions in inner model...</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:06 -#> </div><div class='output co'>#> <span class='message'>→ finding duplicate expressions in EBE model...</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:00 -#> </div><div class='output co'>#> <span class='message'>→ optimizing duplicate expressions in EBE model...</span></div><div class='output co'>#> [====|====|====|====|====|====|====|====|====|====] 0:00:00 -#> </div><div class='output co'>#> <span class='message'>→ compiling inner model...</span></div><div class='output co'>#> <span class='message'> </span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ finding duplicate expressions in FD model...</span></div><div class='output co'>#> </div><div class='output co'>#> <span class='message'>→ optimizing duplicate expressions in FD model...</span></div><div class='output co'>#> </div><div class='output co'>#> <span class='message'>→ compiling EBE model...</span></div><div class='output co'>#> <span class='message'> </span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>→ compiling events FD model...</span></div><div class='output co'>#> <span class='message'> </span></div><div class='output co'>#> <span class='message'><span style='color: #00BB00;'>✔</span> done</span></div><div class='output co'>#> <span class='message'>Model:</span></div><div class='output co'>#> <span class='message'>cmt(DMTA);</span> -#> <span class='message'>cmt(M23);</span> -#> <span class='message'>cmt(M27);</span> -#> <span class='message'>cmt(M31);</span> -#> <span class='message'>rx_expr_14~ETA[1]+THETA[1];</span> -#> <span class='message'>DMTA(0)=rx_expr_14;</span> -#> <span class='message'>rx_expr_15~ETA[5]+THETA[5];</span> -#> <span class='message'>rx_expr_16~ETA[7]+THETA[7];</span> -#> <span class='message'>rx_expr_17~ETA[6]+THETA[6];</span> -#> <span class='message'>rx_expr_24~exp(rx_expr_15);</span> -#> <span class='message'>rx_expr_25~exp(rx_expr_17);</span> -#> <span class='message'>rx_expr_29~t*rx_expr_24;</span> -#> <span class='message'>rx_expr_30~t*rx_expr_25;</span> -#> <span class='message'>rx_expr_31~exp(-(rx_expr_16));</span> -#> <span class='message'>rx_expr_35~1+rx_expr_31;</span> -#> <span class='message'>rx_expr_40~1/(rx_expr_35);</span> -#> <span class='message'>rx_expr_42~(rx_expr_40);</span> -#> <span class='message'>rx_expr_43~1-rx_expr_42;</span> -#> <span class='message'>d/dt(DMTA)=-DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> -#> <span class='message'>rx_expr_18~ETA[2]+THETA[2];</span> -#> <span class='message'>rx_expr_26~exp(rx_expr_18);</span> -#> <span class='message'>d/dt(M23)=-rx_expr_26*M23+DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_1/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> -#> <span class='message'>rx_expr_19~ETA[3]+THETA[3];</span> -#> <span class='message'>rx_expr_20~ETA[4]+THETA[4];</span> -#> <span class='message'>rx_expr_21~1-f_DMTA_tffm0_1;</span> -#> <span class='message'>rx_expr_27~exp(rx_expr_19);</span> -#> <span class='message'>rx_expr_28~exp(rx_expr_20);</span> -#> <span class='message'>d/dt(M27)=-rx_expr_27*M27+rx_expr_28*M31+DMTA*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_2/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> -#> <span class='message'>rx_expr_22~1-f_DMTA_tffm0_2;</span> -#> <span class='message'>d/dt(M31)=-rx_expr_28*M31+DMTA*(rx_expr_22)*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_3/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> -#> <span class='message'>rx_expr_0~CMT==4;</span> -#> <span class='message'>rx_expr_1~CMT==2;</span> -#> <span class='message'>rx_expr_2~CMT==1;</span> -#> <span class='message'>rx_expr_3~CMT==3;</span> -#> <span class='message'>rx_expr_4~1-(rx_expr_0);</span> -#> <span class='message'>rx_expr_5~1-(rx_expr_1);</span> -#> <span class='message'>rx_expr_6~1-(rx_expr_3);</span> -#> <span class='message'>rx_yj_~(rx_expr_4)*((2*(rx_expr_5)*(rx_expr_2)+2*(rx_expr_1))*(rx_expr_6)+2*(rx_expr_3))+2*(rx_expr_0);</span> -#> <span class='message'>rx_expr_7~(rx_expr_1);</span> -#> <span class='message'>rx_expr_8~(rx_expr_3);</span> -#> <span class='message'>rx_expr_9~(rx_expr_0);</span> -#> <span class='message'>rx_expr_13~(rx_expr_5);</span> -#> <span class='message'>rx_expr_32~rx_expr_13*(rx_expr_2);</span> -#> <span class='message'>rx_lambda_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span> -#> <span class='message'>rx_hi_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span> -#> <span class='message'>rx_low_~0;</span> -#> <span class='message'>rx_expr_10~M31*(rx_expr_0);</span> -#> <span class='message'>rx_expr_11~M27*(rx_expr_3);</span> -#> <span class='message'>rx_expr_12~M23*(rx_expr_1);</span> -#> <span class='message'>rx_expr_23~DMTA*(rx_expr_5);</span> -#> <span class='message'>rx_expr_36~rx_expr_23*(rx_expr_2);</span> -#> <span class='message'>rx_pred_=(rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)));</span> -#> <span class='message'>rx_expr_33~Rx_pow_di(THETA[12],2);</span> -#> <span class='message'>rx_expr_34~Rx_pow_di(THETA[11],2);</span> -#> <span class='message'>rx_r_=(rx_expr_4)*((rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6)),2)+rx_expr_34)*(rx_expr_3)+((rx_expr_1)*(rx_expr_33*Rx_pow_di(((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)+(rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)*(rx_expr_5)*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_33*Rx_pow_di(((rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))),2)+rx_expr_34);</span> -#> <span class='message'>DMTA_0=THETA[1];</span> -#> <span class='message'>log_k_M23=THETA[2];</span> -#> <span class='message'>log_k_M27=THETA[3];</span> -#> <span class='message'>log_k_M31=THETA[4];</span> -#> <span class='message'>log_k1=THETA[5];</span> -#> <span class='message'>log_k2=THETA[6];</span> -#> <span class='message'>g_qlogis=THETA[7];</span> -#> <span class='message'>f_DMTA_tffm0_1_qlogis=THETA[8];</span> -#> <span class='message'>f_DMTA_tffm0_2_qlogis=THETA[9];</span> -#> <span class='message'>f_DMTA_tffm0_3_qlogis=THETA[10];</span> -#> <span class='message'>sigma_low=THETA[11];</span> -#> <span class='message'>rsd_high=THETA[12];</span> -#> <span class='message'>eta.DMTA_0=ETA[1];</span> -#> <span class='message'>eta.log_k_M23=ETA[2];</span> -#> <span class='message'>eta.log_k_M27=ETA[3];</span> -#> <span class='message'>eta.log_k_M31=ETA[4];</span> -#> <span class='message'>eta.log_k1=ETA[5];</span> -#> <span class='message'>eta.log_k2=ETA[6];</span> -#> <span class='message'>eta.g_qlogis=ETA[7];</span> -#> <span class='message'>eta.f_DMTA_tffm0_1_qlogis=ETA[8];</span> -#> <span class='message'>eta.f_DMTA_tffm0_2_qlogis=ETA[9];</span> -#> <span class='message'>eta.f_DMTA_tffm0_3_qlogis=ETA[10];</span> -#> <span class='message'>DMTA_0_model=rx_expr_14;</span> -#> <span class='message'>k_M23=rx_expr_26;</span> -#> <span class='message'>k_M27=rx_expr_27;</span> -#> <span class='message'>k_M31=rx_expr_28;</span> -#> <span class='message'>k1=rx_expr_24;</span> -#> <span class='message'>k2=rx_expr_25;</span> -#> <span class='message'>g=1/(rx_expr_35);</span> -#> <span class='message'>f_DMTA_to_M23=1/(1+exp(-(ETA[8]+THETA[8])));</span> -#> <span class='message'>f_DMTA_to_M23=1/(1+exp(-(ETA[9]+THETA[9])));</span> -#> <span class='message'>f_DMTA_to_M23=1/(1+exp(-(ETA[10]+THETA[10])));</span> -#> <span class='message'>f_DMTA_to_M23=f_DMTA_tffm0_1;</span> -#> <span class='message'>f_DMTA_to_M27=(rx_expr_21)*f_DMTA_tffm0_2;</span> -#> <span class='message'>f_DMTA_to_M31=(rx_expr_22)*(rx_expr_21)*f_DMTA_tffm0_3;</span> -#> <span class='message'>tad=tad();</span> -#> <span class='message'>dosenum=dosenum();</span></div><div class='output co'>#> <span class='message'>Needed Covariates:</span></div><div class='output co'>#> <span class='message'>[1] "f_DMTA_tffm0_1" "f_DMTA_tffm0_2" "f_DMTA_tffm0_3" "CMT" </span></div><div class='output co'>#> <span class='error'>Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.</span></div><div class='output co'>#> <span class='message'>Timing stopped at: 121.4 8.294 129.7</span></div><div class='output co'>#> <span class='message'>Timing stopped at: 121.5 8.294 129.9</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/r/base/summary.html'>summary</a></span><span class='op'>(</span><span class='va'>f_dmta_nlmixr_focei</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='error'>Error in summary(f_dmta_nlmixr_focei): object 'f_dmta_nlmixr_focei' not found</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/r/graphics/plot.default.html'>plot</a></span><span class='op'>(</span><span class='va'>f_dmta_nlmixr_focei</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='error'>Error in plot(f_dmta_nlmixr_focei): object 'f_dmta_nlmixr_focei' not found</span></div><div class='input'><span class='co'># Using saemix takes about 18 minutes</span> -<span class='fu'><a href='https://rdrr.io/r/base/system.time.html'>system.time</a></span><span class='op'>(</span> - <span class='va'>f_dmta_saemix</span> <span class='op'><-</span> <span class='fu'><a href='saem.html'>saem</a></span><span class='op'>(</span><span class='va'>f_dmta_mkin_tc</span>, test_log_parms <span class='op'>=</span> <span class='cn'>TRUE</span><span class='op'>)</span> -<span class='op'>)</span> -</div><div class='output co'>#> Running main SAEM algorithm -#> [1] "Tue Oct 5 16:58:50 2021" -#> .... -#> Minimisation finished -#> [1] "Tue Oct 5 17:17:24 2021"</div><div class='output co'>#> user system elapsed -#> 1181.365 0.031 1181.470 </div><div class='input'> -<span class='co'># nlmixr with est = "saem" is pretty fast with default iteration numbers, most</span> -<span class='co'># of the time (about 2.5 minutes) is spent for calculating the log likelihood at the end</span> -<span class='co'># The likelihood calculated for the nlmixr fit is much lower than that found by saemix</span> -<span class='co'># Also, the trace plot and the plot of the individual predictions is not</span> -<span class='co'># convincing for the parent. It seems we are fitting an overparameterised</span> -<span class='co'># model, so the result we get strongly depends on starting parameters and control settings.</span> -<span class='fu'><a href='https://rdrr.io/r/base/system.time.html'>system.time</a></span><span class='op'>(</span> - <span class='va'>f_dmta_nlmixr_saem</span> <span class='op'><-</span> <span class='fu'><a href='https://rdrr.io/pkg/nlmixr/man/nlmixr.html'>nlmixr</a></span><span class='op'>(</span><span class='va'>f_dmta_mkin_tc</span>, est <span class='op'>=</span> <span class='st'>"saem"</span>, - control <span class='op'>=</span> <span class='fu'>nlmixr</span><span class='fu'>::</span><span class='fu'><a href='https://rdrr.io/pkg/nlmixr/man/saemControl.html'>saemControl</a></span><span class='op'>(</span>print <span class='op'>=</span> <span class='fl'>500</span>, logLik <span class='op'>=</span> <span class='cn'>TRUE</span>, nmc <span class='op'>=</span> <span class='fl'>9</span><span class='op'>)</span><span class='op'>)</span> -<span class='op'>)</span> -</div><div class='output co'>#> <span class='message'>With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span></div><div class='output co'>#> <span class='warning'>Warning: number of items to replace is not a multiple of replacement length</span></div><div class='output co'>#> <span class='message'><span style='color: #00BBBB;'>ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span></div><div class='output co'>#> <span class='message'><span style='color: #00BBBB;'>ℹ</span> Need to run with the source intact to parse comments</span></div><div class='output co'>#> <span class='error'>Error in eval(substitute(expr), data, enclos = parent.frame()): Cannot run SAEM since some of the parameters are not mu-referenced (eta.f_DMTA_tffm0_1_qlogis, eta.f_DMTA_tffm0_2_qlogis, eta.f_DMTA_tffm0_3_qlogis)</span></div><div class='output co'>#> <span class='message'>Timing stopped at: 0.849 0.016 0.864</span></div><div class='output co'>#> <span class='message'>Timing stopped at: 1.041 0.016 1.058</span></div><div class='input'><span class='fu'>traceplot</span><span class='op'>(</span><span class='va'>f_dmta_nlmixr_saem</span><span class='op'>$</span><span class='va'>nm</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='error'>Error in traceplot(f_dmta_nlmixr_saem$nm): could not find function "traceplot"</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/r/base/summary.html'>summary</a></span><span class='op'>(</span><span class='va'>f_dmta_nlmixr_saem</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='error'>Error in summary(f_dmta_nlmixr_saem): object 'f_dmta_nlmixr_saem' not found</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/r/graphics/plot.default.html'>plot</a></span><span class='op'>(</span><span class='va'>f_dmta_nlmixr_saem</span><span class='op'>)</span> -</div><div class='output co'>#> <span class='error'>Error in plot(f_dmta_nlmixr_saem): object 'f_dmta_nlmixr_saem' not found</span></div><div class='input'><span class='co'># }</span> -</div></pre> + <div id="ref-examples"> + <h2>Examples</h2> + <div class="sourceCode"><pre class="sourceCode r"><code><span class="r-in"><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">dimethenamid_2018</span><span class="op">)</span></span> +<span class="r-out co"><span class="r-pr">#></span> <mkindsg> holding 7 mkinds objects</span> +<span class="r-out co"><span class="r-pr">#></span> Title $title: Aerobic soil degradation data on dimethenamid-P from the EU assessment in 2018 </span> +<span class="r-out co"><span class="r-pr">#></span> Occurrence of observed compounds $observed_n:</span> +<span class="r-out co"><span class="r-pr">#></span> DMTAP M23 M27 M31 DMTA </span> +<span class="r-out co"><span class="r-pr">#></span> 3 7 7 7 4 </span> +<span class="r-out co"><span class="r-pr">#></span> Time normalisation factors $f_time_norm:</span> +<span class="r-out co"><span class="r-pr">#></span> [1] 1.0000000 0.9706477 1.2284784 1.2284784 0.6233856 0.7678922 0.6733938</span> +<span class="r-out co"><span class="r-pr">#></span> Meta information $meta:</span> +<span class="r-out co"><span class="r-pr">#></span> study usda_soil_type study_moisture_ref_type rel_moisture</span> +<span class="r-out co"><span class="r-pr">#></span> Calke Unsworth 2014 Sandy loam pF2 1.00</span> +<span class="r-out co"><span class="r-pr">#></span> Borstel Staudenmaier 2009 Sand pF1 0.50</span> +<span class="r-out co"><span class="r-pr">#></span> Elliot 1 Wendt 1997 Clay loam pF2.5 0.75</span> +<span class="r-out co"><span class="r-pr">#></span> Elliot 2 Wendt 1997 Clay loam pF2.5 0.75</span> +<span class="r-out co"><span class="r-pr">#></span> Flaach König 1996 Sandy clay loam pF1 0.40</span> +<span class="r-out co"><span class="r-pr">#></span> BBA 2.2 König 1995 Loamy sand pF1 0.40</span> +<span class="r-out co"><span class="r-pr">#></span> BBA 2.3 König 1995 Sandy loam pF1 0.40</span> +<span class="r-out co"><span class="r-pr">#></span> study_ref_moisture temperature</span> +<span class="r-out co"><span class="r-pr">#></span> Calke NA 20</span> +<span class="r-out co"><span class="r-pr">#></span> Borstel 23.00 20</span> +<span class="r-out co"><span class="r-pr">#></span> Elliot 1 33.37 23</span> +<span class="r-out co"><span class="r-pr">#></span> Elliot 2 33.37 23</span> +<span class="r-out co"><span class="r-pr">#></span> Flaach NA 20</span> +<span class="r-out co"><span class="r-pr">#></span> BBA 2.2 NA 20</span> +<span class="r-out co"><span class="r-pr">#></span> BBA 2.3 NA 20</span> +<span class="r-in"><span class="va">dmta_ds</span> <span class="op"><-</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="fl">1</span><span class="op">:</span><span class="fl">7</span>, <span class="kw">function</span><span class="op">(</span><span class="va">i</span><span class="op">)</span> <span class="op">{</span></span> +<span class="r-in"> <span class="va">ds_i</span> <span class="op"><-</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span><span class="op">[[</span><span class="va">i</span><span class="op">]</span><span class="op">]</span><span class="op">$</span><span class="va">data</span></span> +<span class="r-in"> <span class="va">ds_i</span><span class="op">[</span><span class="va">ds_i</span><span class="op">$</span><span class="va">name</span> <span class="op">==</span> <span class="st">"DMTAP"</span>, <span class="st">"name"</span><span class="op">]</span> <span class="op"><-</span> <span class="st">"DMTA"</span></span> +<span class="r-in"> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op"><-</span> <span class="va">ds_i</span><span class="op">$</span><span class="va">time</span> <span class="op">*</span> <span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">f_time_norm</span><span class="op">[</span><span class="va">i</span><span class="op">]</span></span> +<span class="r-in"> <span class="va">ds_i</span></span> +<span class="r-in"><span class="op">}</span><span class="op">)</span></span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/names.html" class="external-link">names</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">)</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/lapply.html" class="external-link">sapply</a></span><span class="op">(</span><span class="va">dimethenamid_2018</span><span class="op">$</span><span class="va">ds</span>, <span class="kw">function</span><span class="op">(</span><span class="va">ds</span><span class="op">)</span> <span class="va">ds</span><span class="op">$</span><span class="va">title</span><span class="op">)</span></span> +<span class="r-in"><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/r/base/cbind.html" class="external-link">rbind</a></span><span class="op">(</span><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span>, <span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span><span class="op">)</span></span> +<span class="r-in"><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 1"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span></span> +<span class="r-in"><span class="va">dmta_ds</span><span class="op">[[</span><span class="st">"Elliot 2"</span><span class="op">]</span><span class="op">]</span> <span class="op"><-</span> <span class="cn">NULL</span></span> +<span class="r-in"><span class="co"># \dontrun{</span></span> +<span class="r-in"><span class="va">dfop_sfo3_plus</span> <span class="op"><-</span> <span class="fu"><a href="mkinmod.html">mkinmod</a></span><span class="op">(</span></span> +<span class="r-in"> DMTA <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="fu"><a href="https://rdrr.io/r/base/c.html" class="external-link">c</a></span><span class="op">(</span><span class="st">"M23"</span>, <span class="st">"M27"</span>, <span class="st">"M31"</span><span class="op">)</span><span class="op">)</span>,</span> +<span class="r-in"> M23 <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> +<span class="r-in"> M27 <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> +<span class="r-in"> M31 <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">"M27"</span>, sink <span class="op">=</span> <span class="cn">FALSE</span><span class="op">)</span>,</span> +<span class="r-in"> quiet <span class="op">=</span> <span class="cn">TRUE</span></span> +<span class="r-in"><span class="op">)</span></span> +<span class="r-in"><span class="va">f_dmta_mkin_tc</span> <span class="op"><-</span> <span class="fu"><a href="mmkin.html">mmkin</a></span><span class="op">(</span></span> +<span class="r-in"> <span class="fu"><a href="https://rdrr.io/r/base/list.html" class="external-link">list</a></span><span class="op">(</span><span class="st">"DFOP-SFO3+"</span> <span class="op">=</span> <span class="va">dfop_sfo3_plus</span><span class="op">)</span>,</span> +<span class="r-in"> <span class="va">dmta_ds</span>, quiet <span class="op">=</span> <span class="cn">TRUE</span>, error_model <span class="op">=</span> <span class="st">"tc"</span><span class="op">)</span></span> +<span class="r-in"><span class="fu"><a href="nlmixr.mmkin.html">nlmixr_model</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span><span class="op">)</span></span> +<span class="r-msg co"><span class="r-pr">#></span> With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span> +<span class="r-wrn co"><span class="r-pr">#></span> <span class="warning">Warning: </span>number of items to replace is not a multiple of replacement length</span> +<span class="r-out co"><span class="r-pr">#></span> function () </span> +<span class="r-out co"><span class="r-pr">#></span> {</span> +<span class="r-out co"><span class="r-pr">#></span> ini({</span> +<span class="r-out co"><span class="r-pr">#></span> DMTA_0 = 99</span> +<span class="r-out co"><span class="r-pr">#></span> eta.DMTA_0 ~ 2.3</span> +<span class="r-out co"><span class="r-pr">#></span> log_k_M23 = -3.9</span> +<span class="r-out co"><span class="r-pr">#></span> eta.log_k_M23 ~ 0.55</span> +<span class="r-out co"><span class="r-pr">#></span> log_k_M27 = -4.3</span> +<span class="r-out co"><span class="r-pr">#></span> eta.log_k_M27 ~ 0.86</span> +<span class="r-out co"><span class="r-pr">#></span> log_k_M31 = -4.2</span> +<span class="r-out co"><span class="r-pr">#></span> eta.log_k_M31 ~ 0.75</span> +<span class="r-out co"><span class="r-pr">#></span> log_k1 = -2.2</span> +<span class="r-out co"><span class="r-pr">#></span> eta.log_k1 ~ 0.9</span> +<span class="r-out co"><span class="r-pr">#></span> log_k2 = -3.8</span> +<span class="r-out co"><span class="r-pr">#></span> eta.log_k2 ~ 1.6</span> +<span class="r-out co"><span class="r-pr">#></span> g_qlogis = 0.44</span> +<span class="r-out co"><span class="r-pr">#></span> eta.g_qlogis ~ 3.1</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_1_qlogis = -2.1</span> +<span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_1_qlogis ~ 0.3</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_2_qlogis = -2.2</span> +<span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_2_qlogis ~ 0.3</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_tffm0_3_qlogis = -2.1</span> +<span class="r-out co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_3_qlogis ~ 0.3</span> +<span class="r-out co"><span class="r-pr">#></span> sigma_low_DMTA = 0.7</span> +<span class="r-out co"><span class="r-pr">#></span> rsd_high_DMTA = 0.026</span> +<span class="r-out co"><span class="r-pr">#></span> sigma_low_M23 = 0.7</span> +<span class="r-out co"><span class="r-pr">#></span> rsd_high_M23 = 0.026</span> +<span class="r-out co"><span class="r-pr">#></span> sigma_low_M27 = 0.7</span> +<span class="r-out co"><span class="r-pr">#></span> rsd_high_M27 = 0.026</span> +<span class="r-out co"><span class="r-pr">#></span> sigma_low_M31 = 0.7</span> +<span class="r-out co"><span class="r-pr">#></span> rsd_high_M31 = 0.026</span> +<span class="r-out co"><span class="r-pr">#></span> })</span> +<span class="r-out co"><span class="r-pr">#></span> model({</span> +<span class="r-out co"><span class="r-pr">#></span> DMTA_0_model = DMTA_0 + eta.DMTA_0</span> +<span class="r-out co"><span class="r-pr">#></span> DMTA(0) = DMTA_0_model</span> +<span class="r-out co"><span class="r-pr">#></span> k_M23 = exp(log_k_M23 + eta.log_k_M23)</span> +<span class="r-out co"><span class="r-pr">#></span> k_M27 = exp(log_k_M27 + eta.log_k_M27)</span> +<span class="r-out co"><span class="r-pr">#></span> k_M31 = exp(log_k_M31 + eta.log_k_M31)</span> +<span class="r-out co"><span class="r-pr">#></span> k1 = exp(log_k1 + eta.log_k1)</span> +<span class="r-out co"><span class="r-pr">#></span> k2 = exp(log_k2 + eta.log_k2)</span> +<span class="r-out co"><span class="r-pr">#></span> g = expit(g_qlogis + eta.g_qlogis)</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis)</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis)</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M23 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis)</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M23 = f_DMTA_tffm0_1</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M27 = f_DMTA_tffm0_2 * (1 - f_DMTA_tffm0_1)</span> +<span class="r-out co"><span class="r-pr">#></span> f_DMTA_to_M31 = f_DMTA_tffm0_3 * (1 - f_DMTA_tffm0_2) * </span> +<span class="r-out co"><span class="r-pr">#></span> (1 - f_DMTA_tffm0_1)</span> +<span class="r-out co"><span class="r-pr">#></span> d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 - </span> +<span class="r-out co"><span class="r-pr">#></span> g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 - </span> +<span class="r-out co"><span class="r-pr">#></span> g) * exp(-k2 * time))) * DMTA</span> +<span class="r-out co"><span class="r-pr">#></span> d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23</span> +<span class="r-out co"><span class="r-pr">#></span> d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 + </span> +<span class="r-out co"><span class="r-pr">#></span> k_M31 * M31</span> +<span class="r-out co"><span class="r-pr">#></span> d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) + </span> +<span class="r-out co"><span class="r-pr">#></span> (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31</span> +<span class="r-out co"><span class="r-pr">#></span> DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)</span> +<span class="r-out co"><span class="r-pr">#></span> M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)</span> +<span class="r-out co"><span class="r-pr">#></span> M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)</span> +<span class="r-out co"><span class="r-pr">#></span> M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)</span> +<span class="r-out co"><span class="r-pr">#></span> })</span> +<span class="r-out co"><span class="r-pr">#></span> }</span> +<span class="r-out co"><span class="r-pr">#></span> <environment: 0x55555fca3790></span> +<span class="r-in"><span class="co"># The focei fit takes about four minutes on my system</span></span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span></span> +<span class="r-in"> <span class="va">f_dmta_nlmixr_focei</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span>, est <span class="op">=</span> <span class="st">"focei"</span>,</span> +<span class="r-in"> control <span class="op">=</span> <span class="fu">nlmixr</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/foceiControl.html" class="external-link">foceiControl</a></span><span class="op">(</span>print <span class="op">=</span> <span class="fl">500</span><span class="op">)</span><span class="op">)</span></span> +<span class="r-in"><span class="op">)</span></span> +<span class="r-wrn co"><span class="r-pr">#></span> <span class="warning">Warning: </span>number of items to replace is not a multiple of replacement length</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BBBB;">ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BBBB;">ℹ</span> Need to run with the source intact to parse comments</span> +<span class="r-msg co"><span class="r-pr">#></span> → creating full model...</span> +<span class="r-msg co"><span class="r-pr">#></span> → pruning branches (`if`/`else`)...</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → creating full model...</span> +<span class="r-msg co"><span class="r-pr">#></span> → pruning branches (`if`/`else`)...</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → loading into <span style="color: #0000BB;">symengine</span> environment...</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → calculate jacobian</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → calculate sensitivities</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:03 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → calculate ∂(f)/∂(η)</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:01 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → calculate ∂(R²)/∂(η)</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:08 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in inner model...</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:07 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in inner model...</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:06 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in EBE model...</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in EBE model...</span> +<span class="r-out co"><span class="r-pr">#></span> [====|====|====|====|====|====|====|====|====|====] 0:00:00 </span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → compiling inner model...</span> +<span class="r-msg co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → finding duplicate expressions in FD model...</span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → optimizing duplicate expressions in FD model...</span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> → compiling EBE model...</span> +<span class="r-msg co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> → compiling events FD model...</span> +<span class="r-msg co"><span class="r-pr">#></span> </span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BB00;">✔</span> done</span> +<span class="r-msg co"><span class="r-pr">#></span> Model:</span> +<span class="r-msg co"><span class="r-pr">#></span> cmt(DMTA);</span> +<span class="r-msg co"><span class="r-pr">#></span> cmt(M23);</span> +<span class="r-msg co"><span class="r-pr">#></span> cmt(M27);</span> +<span class="r-msg co"><span class="r-pr">#></span> cmt(M31);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_14~ETA[1]+THETA[1];</span> +<span class="r-msg co"><span class="r-pr">#></span> DMTA(0)=rx_expr_14;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_15~ETA[5]+THETA[5];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_16~ETA[7]+THETA[7];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_17~ETA[6]+THETA[6];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_24~exp(rx_expr_15);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_25~exp(rx_expr_17);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_29~t*rx_expr_24;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_30~t*rx_expr_25;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_31~exp(-(rx_expr_16));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_35~1+rx_expr_31;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_40~1/(rx_expr_35);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_42~(rx_expr_40);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_43~1-rx_expr_42;</span> +<span class="r-msg co"><span class="r-pr">#></span> d/dt(DMTA)=-DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_18~ETA[2]+THETA[2];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_26~exp(rx_expr_18);</span> +<span class="r-msg co"><span class="r-pr">#></span> d/dt(M23)=-rx_expr_26*M23+DMTA*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_1/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_19~ETA[3]+THETA[3];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_20~ETA[4]+THETA[4];</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_21~1-f_DMTA_tffm0_1;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_27~exp(rx_expr_19);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_28~exp(rx_expr_20);</span> +<span class="r-msg co"><span class="r-pr">#></span> d/dt(M27)=-rx_expr_27*M27+rx_expr_28*M31+DMTA*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_2/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_22~1-f_DMTA_tffm0_2;</span> +<span class="r-msg co"><span class="r-pr">#></span> d/dt(M31)=-rx_expr_28*M31+DMTA*(rx_expr_22)*(rx_expr_21)*(exp(rx_expr_15-rx_expr_29)/(rx_expr_35)+exp(rx_expr_17-rx_expr_30)*(rx_expr_43))*f_DMTA_tffm0_3/(exp(-t*rx_expr_24)/(rx_expr_35)+exp(-t*rx_expr_25)*(rx_expr_43));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_0~CMT==4;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_1~CMT==2;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_2~CMT==1;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_3~CMT==3;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_4~1-(rx_expr_0);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_5~1-(rx_expr_1);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_6~1-(rx_expr_3);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_yj_~(rx_expr_4)*((2*(rx_expr_5)*(rx_expr_2)+2*(rx_expr_1))*(rx_expr_6)+2*(rx_expr_3))+2*(rx_expr_0);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_7~(rx_expr_1);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_8~(rx_expr_3);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_9~(rx_expr_0);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_13~(rx_expr_5);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_32~rx_expr_13*(rx_expr_2);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_lambda_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_hi_~(rx_expr_4)*((rx_expr_32+rx_expr_7)*(rx_expr_6)+rx_expr_8)+rx_expr_9;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_low_~0;</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_10~M31*(rx_expr_0);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_11~M27*(rx_expr_3);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_12~M23*(rx_expr_1);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_23~DMTA*(rx_expr_5);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_36~rx_expr_23*(rx_expr_2);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_pred_=(rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)));</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_33~Rx_pow_di(THETA[12],2);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_expr_34~Rx_pow_di(THETA[11],2);</span> +<span class="r-msg co"><span class="r-pr">#></span> rx_r_=(rx_expr_4)*((rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6)),2)+rx_expr_34)*(rx_expr_3)+((rx_expr_1)*(rx_expr_33*Rx_pow_di(((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)+(rx_expr_33*Rx_pow_di(((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2)),2)+rx_expr_34)*(rx_expr_5)*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_33*Rx_pow_di(((rx_expr_4)*((rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_3)+((rx_expr_1)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))+(rx_expr_5)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))*(rx_expr_2))*(rx_expr_6))+(rx_expr_0)*(rx_expr_10+(rx_expr_4)*(rx_expr_11+(rx_expr_12+rx_expr_36)*(rx_expr_6)))),2)+rx_expr_34);</span> +<span class="r-msg co"><span class="r-pr">#></span> DMTA_0=THETA[1];</span> +<span class="r-msg co"><span class="r-pr">#></span> log_k_M23=THETA[2];</span> +<span class="r-msg co"><span class="r-pr">#></span> log_k_M27=THETA[3];</span> +<span class="r-msg co"><span class="r-pr">#></span> log_k_M31=THETA[4];</span> +<span class="r-msg co"><span class="r-pr">#></span> log_k1=THETA[5];</span> +<span class="r-msg co"><span class="r-pr">#></span> log_k2=THETA[6];</span> +<span class="r-msg co"><span class="r-pr">#></span> g_qlogis=THETA[7];</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_1_qlogis=THETA[8];</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_2_qlogis=THETA[9];</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_tffm0_3_qlogis=THETA[10];</span> +<span class="r-msg co"><span class="r-pr">#></span> sigma_low=THETA[11];</span> +<span class="r-msg co"><span class="r-pr">#></span> rsd_high=THETA[12];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.DMTA_0=ETA[1];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M23=ETA[2];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M27=ETA[3];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.log_k_M31=ETA[4];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.log_k1=ETA[5];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.log_k2=ETA[6];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.g_qlogis=ETA[7];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_1_qlogis=ETA[8];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_2_qlogis=ETA[9];</span> +<span class="r-msg co"><span class="r-pr">#></span> eta.f_DMTA_tffm0_3_qlogis=ETA[10];</span> +<span class="r-msg co"><span class="r-pr">#></span> DMTA_0_model=rx_expr_14;</span> +<span class="r-msg co"><span class="r-pr">#></span> k_M23=rx_expr_26;</span> +<span class="r-msg co"><span class="r-pr">#></span> k_M27=rx_expr_27;</span> +<span class="r-msg co"><span class="r-pr">#></span> k_M31=rx_expr_28;</span> +<span class="r-msg co"><span class="r-pr">#></span> k1=rx_expr_24;</span> +<span class="r-msg co"><span class="r-pr">#></span> k2=rx_expr_25;</span> +<span class="r-msg co"><span class="r-pr">#></span> g=1/(rx_expr_35);</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[8]+THETA[8])));</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[9]+THETA[9])));</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=1/(1+exp(-(ETA[10]+THETA[10])));</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M23=f_DMTA_tffm0_1;</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M27=(rx_expr_21)*f_DMTA_tffm0_2;</span> +<span class="r-msg co"><span class="r-pr">#></span> f_DMTA_to_M31=(rx_expr_22)*(rx_expr_21)*f_DMTA_tffm0_3;</span> +<span class="r-msg co"><span class="r-pr">#></span> tad=tad();</span> +<span class="r-msg co"><span class="r-pr">#></span> dosenum=dosenum();</span> +<span class="r-msg co"><span class="r-pr">#></span> Needed Covariates:</span> +<span class="r-msg co"><span class="r-pr">#></span> [1] "f_DMTA_tffm0_1" "f_DMTA_tffm0_2" "f_DMTA_tffm0_3" "CMT" </span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop):</span> Not all the covariates are in the dataset.</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 119.8 9.331 129.2</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 120 9.331 129.3</span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/summary.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_focei</span><span class="op">)</span></span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in summary(f_dmta_nlmixr_focei):</span> object 'f_dmta_nlmixr_focei' not found</span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_focei</span><span class="op">)</span></span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in plot(f_dmta_nlmixr_focei):</span> object 'f_dmta_nlmixr_focei' not found</span> +<span class="r-in"><span class="co"># Using saemix takes about 18 minutes</span></span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span></span> +<span class="r-in"> <span class="va">f_dmta_saemix</span> <span class="op"><-</span> <span class="fu"><a href="saem.html">saem</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span>, test_log_parms <span class="op">=</span> <span class="cn">TRUE</span><span class="op">)</span></span> +<span class="r-in"><span class="op">)</span></span> +<span class="r-out co"><span class="r-pr">#></span> DINTDY- T (=R1) illegal </span> +<span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 115.507</span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-out co"><span class="r-pr">#></span> T not in interval TCUR - HU (= R1) to TCUR (=R2) </span> +<span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 112.133, R2 = 113.577</span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-out co"><span class="r-pr">#></span> DLSODA- At T (=R1), too much accuracy requested </span> +<span class="r-out co"><span class="r-pr">#></span> for precision of machine.. See TOLSF (=R2) </span> +<span class="r-out co"><span class="r-pr">#></span> In above message, R1 = 55.3899, R2 = nan</span> +<span class="r-out co"><span class="r-pr">#></span> </span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in out[available, var]:</span> (subscript) logical subscript too long</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 11.84 0.008 11.85</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 12.16 0.008 12.17</span> +<span class="r-in"></span> +<span class="r-in"><span class="co"># nlmixr with est = "saem" is pretty fast with default iteration numbers, most</span></span> +<span class="r-in"><span class="co"># of the time (about 2.5 minutes) is spent for calculating the log likelihood at the end</span></span> +<span class="r-in"><span class="co"># The likelihood calculated for the nlmixr fit is much lower than that found by saemix</span></span> +<span class="r-in"><span class="co"># Also, the trace plot and the plot of the individual predictions is not</span></span> +<span class="r-in"><span class="co"># convincing for the parent. It seems we are fitting an overparameterised</span></span> +<span class="r-in"><span class="co"># model, so the result we get strongly depends on starting parameters and control settings.</span></span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/system.time.html" class="external-link">system.time</a></span><span class="op">(</span></span> +<span class="r-in"> <span class="va">f_dmta_nlmixr_saem</span> <span class="op"><-</span> <span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/nlmixr.html" class="external-link">nlmixr</a></span><span class="op">(</span><span class="va">f_dmta_mkin_tc</span>, est <span class="op">=</span> <span class="st">"saem"</span>,</span> +<span class="r-in"> control <span class="op">=</span> <span class="fu">nlmixr</span><span class="fu">::</span><span class="fu"><a href="https://rdrr.io/pkg/nlmixr/man/saemControl.html" class="external-link">saemControl</a></span><span class="op">(</span>print <span class="op">=</span> <span class="fl">500</span>, logLik <span class="op">=</span> <span class="cn">TRUE</span>, nmc <span class="op">=</span> <span class="fl">9</span><span class="op">)</span><span class="op">)</span></span> +<span class="r-in"><span class="op">)</span></span> +<span class="r-msg co"><span class="r-pr">#></span> With est = 'saem', a different error model is required for each observed variableChanging the error model to 'obs_tc' (Two-component error for each observed variable)</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BBBB;">ℹ</span> parameter labels from comments are typically ignored in non-interactive mode</span> +<span class="r-msg co"><span class="r-pr">#></span> <span style="color: #00BBBB;">ℹ</span> Need to run with the source intact to parse comments</span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in eval(substitute(expr), data, enclos = parent.frame()):</span> Cannot run SAEM since some of the parameters are not mu-referenced (eta.f_DMTA_tffm0_1_qlogis, eta.f_DMTA_tffm0_2_qlogis, eta.f_DMTA_tffm0_3_qlogis)</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 0.892 0.004 0.896</span> +<span class="r-msg co"><span class="r-pr">#></span> Timing stopped at: 1.096 0.005 1.1</span> +<span class="r-in"><span class="fu">traceplot</span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">$</span><span class="va">nm</span><span class="op">)</span></span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in traceplot(f_dmta_nlmixr_saem$nm):</span> could not find function "traceplot"</span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/base/summary.html" class="external-link">summary</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">)</span></span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in summary(f_dmta_nlmixr_saem):</span> object 'f_dmta_nlmixr_saem' not found</span> +<span class="r-in"><span class="fu"><a href="https://rdrr.io/r/graphics/plot.default.html" class="external-link">plot</a></span><span class="op">(</span><span class="va">f_dmta_nlmixr_saem</span><span class="op">)</span></span> +<span class="r-err co"><span class="r-pr">#></span> <span class="error">Error in plot(f_dmta_nlmixr_saem):</span> object 'f_dmta_nlmixr_saem' not found</span> +<span class="r-in"><span class="co"># }</span></span> +</code></pre></div> + </div> </div> <div class="col-md-3 hidden-xs hidden-sm" id="pkgdown-sidebar"> - <nav id="toc" data-toggle="toc" class="sticky-top"> - <h2 data-toc-skip>Contents</h2> - </nav> - </div> + <nav id="toc" data-toggle="toc" class="sticky-top"><h2 data-toc-skip>Contents</h2> + </nav></div> </div> - <footer> - <div class="copyright"> - <p>Developed by Johannes Ranke.</p> + <footer><div class="copyright"> + <p></p><p>Developed by Johannes Ranke.</p> </div> <div class="pkgdown"> - <p>Site built with <a href="https://pkgdown.r-lib.org/">pkgdown</a> 1.6.1.</p> + <p></p><p>Site built with <a href="https://pkgdown.r-lib.org/" class="external-link">pkgdown</a> 2.0.2.</p> </div> - </footer> - </div> + </footer></div> - </body> -</html> + + </body></html> |