Some improvements for borderline cases

- fit_with_errors for saem()
- test_log_parms for mean_degparms() and saem()

1 files changed, 49 insertions, 23 deletions

diff --git a/docs/dev/reference/saem.html b/docs/dev/reference/saem.html
index bdb1226e..23102df3 100644
--- a/docs/dev/reference/saem.html
+++ b/docs/dev/reference/saem.html
@@ -74,7 +74,7 @@ Expectation Maximisation algorithm (SAEM)." />
       </button>
       <span class="navbar-brand">
         <a class="navbar-link" href="../index.html">mkin</a>
-        <span class="version label label-info" data-toggle="tooltip" data-placement="bottom" title="In-development version">1.0.3.9000</span>
+        <span class="version label label-info" data-toggle="tooltip" data-placement="bottom" title="In-development version">1.0.4.9000</span>
       </span>
     </div>
 
@@ -158,9 +158,12 @@ Expectation Maximisation algorithm (SAEM).</p>
   <span class='va'>object</span>,
   transformations <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/c.html'>c</a></span><span class='op'>(</span><span class='st'>"mkin"</span>, <span class='st'>"saemix"</span><span class='op'>)</span>,
   degparms_start <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/numeric.html'>numeric</a></span><span class='op'>(</span><span class='op'>)</span>,
+  test_log_parms <span class='op'>=</span> <span class='cn'>FALSE</span>,
+  conf.level <span class='op'>=</span> <span class='fl'>0.6</span>,
   solution_type <span class='op'>=</span> <span class='st'>"auto"</span>,
   control <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/list.html'>list</a></span><span class='op'>(</span>displayProgress <span class='op'>=</span> <span class='cn'>FALSE</span>, print <span class='op'>=</span> <span class='cn'>FALSE</span>, save <span class='op'>=</span> <span class='cn'>FALSE</span>, save.graphs <span class='op'>=</span>
     <span class='cn'>FALSE</span><span class='op'>)</span>,
+  fail_with_errors <span class='op'>=</span> <span class='cn'>TRUE</span>,
   verbose <span class='op'>=</span> <span class='cn'>FALSE</span>,
   quiet <span class='op'>=</span> <span class='cn'>FALSE</span>,
   <span class='va'>...</span>
@@ -174,6 +177,7 @@ Expectation Maximisation algorithm (SAEM).</p>
   solution_type <span class='op'>=</span> <span class='st'>"auto"</span>,
   transformations <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/c.html'>c</a></span><span class='op'>(</span><span class='st'>"mkin"</span>, <span class='st'>"saemix"</span><span class='op'>)</span>,
   degparms_start <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/numeric.html'>numeric</a></span><span class='op'>(</span><span class='op'>)</span>,
+  test_log_parms <span class='op'>=</span> <span class='cn'>FALSE</span>,
   verbose <span class='op'>=</span> <span class='cn'>FALSE</span>,
   <span class='va'>...</span>
 <span class='op'>)</span>
@@ -206,6 +210,18 @@ SFO or DFOP is used for the parent and there is either no metabolite or one.</p>
 be used to override the starting values obtained from the 'mmkin' object.</p></td>
     </tr>
     <tr>
+      <th>test_log_parms</th>
+      <td><p>If TRUE, an attempt is made to use more robust starting
+values for population parameters fitted as log parameters in mkin (like
+rate constants) by only considering rate constants that pass the t-test
+when calculating mean degradation parameters using <a href='nlme_function.html'>mean_degparms</a>.</p></td>
+    </tr>
+    <tr>
+      <th>conf.level</th>
+      <td><p>Possibility to adjust the required confidence level
+for parameter that are tested if requested by 'test_log_parms'.</p></td>
+    </tr>
+    <tr>
       <th>solution_type</th>
       <td><p>Possibility to specify the solution type in case the
 automatic choice is not desired</p></td>
@@ -215,6 +231,11 @@ automatic choice is not desired</p></td>
       <td><p>Passed to <a href='https://rdrr.io/pkg/saemix/man/saemix.html'>saemix::saemix</a></p></td>
     </tr>
     <tr>
+      <th>fail_with_errors</th>
+      <td><p>Should a failure to compute standard errors
+from the inverse of the Fisher Information Matrix be a failure?</p></td>
+    </tr>
+    <tr>
       <th>verbose</th>
       <td><p>Should we print information about created objects of
 type <a href='https://rdrr.io/pkg/saemix/man/SaemixModel-class.html'>saemix::SaemixModel</a> and <a href='https://rdrr.io/pkg/saemix/man/SaemixData-class.html'>saemix::SaemixData</a>?</p></td>
@@ -261,33 +282,36 @@ using <a href='mmkin.html'>mmkin</a>.</p>
   state.ini <span class='op'>=</span> <span class='fu'><a href='https://rdrr.io/r/base/c.html'>c</a></span><span class='op'>(</span>parent <span class='op'>=</span> <span class='fl'>100</span><span class='op'>)</span>, fixed_initials <span class='op'>=</span> <span class='st'>"parent"</span>, quiet <span class='op'>=</span> <span class='cn'>TRUE</span><span class='op'>)</span>
 <span class='va'>f_saem_p0_fixed</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent_p0_fixed</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:32 2021"
+#&gt; [1] "Tue Mar  9 17:34:44 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:34 2021"</div><div class='input'>
+#&gt; [1] "Tue Mar  9 17:34:45 2021"</div><div class='input'>
 <span class='va'>f_mmkin_parent</span> <span class='op'>&lt;-</span> <span class='fu'><a href='mmkin.html'>mmkin</a></span><span class='op'>(</span><span class='fu'><a href='https://rdrr.io/r/base/c.html'>c</a></span><span class='op'>(</span><span class='st'>"SFO"</span>, <span class='st'>"FOMC"</span>, <span class='st'>"DFOP"</span><span class='op'>)</span>, <span class='va'>ds</span>, quiet <span class='op'>=</span> <span class='cn'>TRUE</span><span class='op'>)</span>
 <span class='va'>f_saem_sfo</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent</span><span class='op'>[</span><span class='st'>"SFO"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:35 2021"
+#&gt; [1] "Tue Mar  9 17:34:46 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:36 2021"</div><div class='input'><span class='va'>f_saem_fomc</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent</span><span class='op'>[</span><span class='st'>"FOMC"</span>, <span class='op'>]</span><span class='op'>)</span>
+#&gt; [1] "Tue Mar  9 17:34:48 2021"</div><div class='input'><span class='va'>f_saem_fomc</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent</span><span class='op'>[</span><span class='st'>"FOMC"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:36 2021"
+#&gt; [1] "Tue Mar  9 17:34:48 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:38 2021"</div><div class='input'><span class='va'>f_saem_dfop</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent</span><span class='op'>[</span><span class='st'>"DFOP"</span>, <span class='op'>]</span><span class='op'>)</span>
+#&gt; [1] "Tue Mar  9 17:34:50 2021"</div><div class='input'><span class='va'>f_saem_dfop</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent</span><span class='op'>[</span><span class='st'>"DFOP"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:39 2021"
+#&gt; [1] "Tue Mar  9 17:34:51 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:42 2021"</div><div class='input'>
+#&gt; [1] "Tue Mar  9 17:34:53 2021"</div><div class='input'>
 <span class='co'># The returned saem.mmkin object contains an SaemixObject, therefore we can use</span>
 <span class='co'># functions from saemix</span>
 <span class='kw'><a href='https://rdrr.io/r/base/library.html'>library</a></span><span class='op'>(</span><span class='va'>saemix</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; <span class='message'>Package saemix, version 3.1.9000</span>
-#&gt; <span class='message'>  please direct bugs, questions and feedback to emmanuelle.comets@inserm.fr</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/compare.saemix.html'>compare.saemix</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='va'>f_saem_sfo</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_dfop</span><span class='op'>$</span><span class='va'>so</span><span class='op'>)</span><span class='op'>)</span>
-</div><div class='output co'>#&gt; <span class='error'>Error in compare.saemix(list(f_saem_sfo$so, f_saem_fomc$so, f_saem_dfop$so)): 'compare.saemix' requires at least two models.</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/plot-SaemixObject-method.html'>plot</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, plot.type <span class='op'>=</span> <span class='st'>"convergence"</span><span class='op'>)</span>
+#&gt; <span class='message'>  please direct bugs, questions and feedback to emmanuelle.comets@inserm.fr</span></div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/compare.saemix.html'>compare.saemix</a></span><span class='op'>(</span><span class='va'>f_saem_sfo</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_dfop</span><span class='op'>$</span><span class='va'>so</span><span class='op'>)</span>
+</div><div class='output co'>#&gt; <span class='message'>Likelihoods calculated by importance sampling</span></div><div class='output co'>#&gt;        AIC      BIC
+#&gt; 1 624.2484 622.2956
+#&gt; 2 467.7096 464.9757
+#&gt; 3 495.4373 491.9222</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/plot-SaemixObject-method.html'>plot</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, plot.type <span class='op'>=</span> <span class='st'>"convergence"</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Plotting convergence plots</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/plot-SaemixObject-method.html'>plot</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, plot.type <span class='op'>=</span> <span class='st'>"individual.fit"</span><span class='op'>)</span>
 </div><div class='img'><img src='saem-1.png' alt='' width='700' height='433' /></div><div class='output co'>#&gt; Plotting individual fits</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/plot-SaemixObject-method.html'>plot</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, plot.type <span class='op'>=</span> <span class='st'>"npde"</span><span class='op'>)</span>
 </div><div class='img'><img src='saem-2.png' alt='' width='700' height='433' /></div><div class='output co'>#&gt; Simulating data using nsim = 1000 simulated datasets
@@ -324,11 +348,13 @@ using <a href='mmkin.html'>mmkin</a>.</p>
 <span class='va'>f_mmkin_parent_tc</span> <span class='op'>&lt;-</span> <span class='fu'><a href='https://rdrr.io/r/stats/update.html'>update</a></span><span class='op'>(</span><span class='va'>f_mmkin_parent</span>, error_model <span class='op'>=</span> <span class='st'>"tc"</span><span class='op'>)</span>
 <span class='va'>f_saem_fomc_tc</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin_parent_tc</span><span class='op'>[</span><span class='st'>"FOMC"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:44 2021"
+#&gt; [1] "Tue Mar  9 17:34:55 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:49 2021"</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/compare.saemix.html'>compare.saemix</a></span><span class='op'>(</span><span class='fu'><a href='https://rdrr.io/r/base/list.html'>list</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_fomc_tc</span><span class='op'>$</span><span class='va'>so</span><span class='op'>)</span><span class='op'>)</span>
-</div><div class='output co'>#&gt; <span class='error'>Error in compare.saemix(list(f_saem_fomc$so, f_saem_fomc_tc$so)): 'compare.saemix' requires at least two models.</span></div><div class='input'>
+#&gt; [1] "Tue Mar  9 17:35:00 2021"</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/compare.saemix.html'>compare.saemix</a></span><span class='op'>(</span><span class='va'>f_saem_fomc</span><span class='op'>$</span><span class='va'>so</span>, <span class='va'>f_saem_fomc_tc</span><span class='op'>$</span><span class='va'>so</span><span class='op'>)</span>
+</div><div class='output co'>#&gt; <span class='message'>Likelihoods calculated by importance sampling</span></div><div class='output co'>#&gt;        AIC      BIC
+#&gt; 1 467.7096 464.9757
+#&gt; 2 469.6831 466.5586</div><div class='input'>
 <span class='va'>sfo_sfo</span> <span class='op'>&lt;-</span> <span class='fu'><a href='mkinmod.html'>mkinmod</a></span><span class='op'>(</span>parent <span class='op'>=</span> <span class='fu'><a href='mkinmod.html'>mkinsub</a></span><span class='op'>(</span><span class='st'>"SFO"</span>, <span class='st'>"A1"</span><span class='op'>)</span>,
   A1 <span class='op'>=</span> <span class='fu'><a href='mkinmod.html'>mkinsub</a></span><span class='op'>(</span><span class='st'>"SFO"</span><span class='op'>)</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; <span class='message'>Temporary DLL for differentials generated and loaded</span></div><div class='input'><span class='va'>fomc_sfo</span> <span class='op'>&lt;-</span> <span class='fu'><a href='mkinmod.html'>mkinmod</a></span><span class='op'>(</span>parent <span class='op'>=</span> <span class='fu'><a href='mkinmod.html'>mkinsub</a></span><span class='op'>(</span><span class='st'>"FOMC"</span>, <span class='st'>"A1"</span><span class='op'>)</span>,
@@ -346,15 +372,15 @@ using <a href='mmkin.html'>mmkin</a>.</p>
 <span class='co'># four minutes</span>
 <span class='va'>f_saem_sfo_sfo</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin</span><span class='op'>[</span><span class='st'>"SFO-SFO"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:51 2021"
+#&gt; [1] "Tue Mar  9 17:35:02 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:12:56 2021"</div><div class='input'><span class='va'>f_saem_dfop_sfo</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin</span><span class='op'>[</span><span class='st'>"DFOP-SFO"</span>, <span class='op'>]</span><span class='op'>)</span>
+#&gt; [1] "Tue Mar  9 17:35:07 2021"</div><div class='input'><span class='va'>f_saem_dfop_sfo</span> <span class='op'>&lt;-</span> <span class='fu'>saem</span><span class='op'>(</span><span class='va'>f_mmkin</span><span class='op'>[</span><span class='st'>"DFOP-SFO"</span>, <span class='op'>]</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Running main SAEM algorithm
-#&gt; [1] "Mon Feb 15 17:12:56 2021"
+#&gt; [1] "Tue Mar  9 17:35:07 2021"
 #&gt; ....
 #&gt;     Minimisation finished
-#&gt; [1] "Mon Feb 15 17:13:05 2021"</div><div class='input'><span class='co'># We can use print, plot and summary methods to check the results</span>
+#&gt; [1] "Tue Mar  9 17:35:15 2021"</div><div class='input'><span class='co'># We can use print, plot and summary methods to check the results</span>
 <span class='fu'><a href='https://rdrr.io/r/base/print.html'>print</a></span><span class='op'>(</span><span class='va'>f_saem_dfop_sfo</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; Kinetic nonlinear mixed-effects model fit by SAEM
 #&gt; Structural model:
@@ -395,10 +421,10 @@ using <a href='mmkin.html'>mmkin</a>.</p>
 #&gt; SD.g_qlogis          0.44771 -0.86417  1.7596</div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/plot-SaemixObject-method.html'>plot</a></span><span class='op'>(</span><span class='va'>f_saem_dfop_sfo</span><span class='op'>)</span>
 </div><div class='img'><img src='saem-5.png' alt='' width='700' height='433' /></div><div class='input'><span class='fu'><a href='https://rdrr.io/pkg/saemix/man/summary-methods.html'>summary</a></span><span class='op'>(</span><span class='va'>f_saem_dfop_sfo</span>, data <span class='op'>=</span> <span class='cn'>TRUE</span><span class='op'>)</span>
 </div><div class='output co'>#&gt; saemix version used for fitting:      3.1.9000 
-#&gt; mkin version used for pre-fitting:  1.0.3.9000 
-#&gt; R version used for fitting:         4.0.3 
-#&gt; Date of fit:     Mon Feb 15 17:13:05 2021 
-#&gt; Date of summary: Mon Feb 15 17:13:06 2021 
+#&gt; mkin version used for pre-fitting:  1.0.4.9000 
+#&gt; R version used for fitting:         4.0.4 
+#&gt; Date of fit:     Tue Mar  9 17:35:16 2021 
+#&gt; Date of summary: Tue Mar  9 17:35:16 2021 
 #&gt; 
 #&gt; Equations:
 #&gt; d_parent/dt = - ((k1 * g * exp(-k1 * time) + k2 * (1 - g) * exp(-k2 *
@@ -413,7 +439,7 @@ using <a href='mmkin.html'>mmkin</a>.</p>
 #&gt; 
 #&gt; Model predictions using solution type analytical 
 #&gt; 
-#&gt; Fitted in 8.985 s using 300, 100 iterations
+#&gt; Fitted in 8.668 s using 300, 100 iterations
 #&gt; 
 #&gt; Variance model: Constant variance 
 #&gt;