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 110 <div id="Layer1"
 111  style="position: absolute; left: 335px; top: 42px; width: 388px; height: 43px; z-index: 1; font-size: x-small;">
 112 <div class="style1" align="right">Stepwise
 113 Covariate Modeling (<span style="font-family: monospace;">scm</span>)<br>
 114 </div>
 115 </div>
 116 <div id="Layer2"
 117  style="position: absolute; left: 226px; width: 497px; z-index: 2; top: 188px; height: 1110px;">
 118 <div align="justify">
 119 <?php
 120 include("scm_synopsis.php");
 121 include("scm_description.php");
 122 php?>
 123 <p class="heading2">Valid states for the parameter-covariate relations</p>
 124
 125 <p>The SCM tool in PsN is written to be flexible in the shape of the
 126 parameter-covariate relations. Currently there is a fixed set of
 127 available forms of relations but there is ongoing development aiming
 128 at full flexibility for the user with regard to relation-shape
 129 definitions.</p>
 130
 131 <p>The avaialable shapes or <em>states</em> for the
 132 parameter-covariate relations for continuous covariates are (1) not
 133 included, (2) included as a linear relation and (3) included as a
 134 piece-wise linear relation with two slopes. </p>
 135
 136 <p>Categorical covariates are either (1) not included or (2) included with an extra parameter added for each but the most common category. </p>
 137 <p>The figures, 1, 2 and 3, are used when specifying included relations below. </p>
 138 <?php
 139 include("scm_options.php");
 140 include("scm_examples.php");
 141 php?>
 142 <!-- <h3 class="heading1">Synopsis</h3>
 143 <p class="style2">$         scm [ -h | -? ] [ --help ]<br>
 144 --config_file='string'<br>
 145 [ --do_not_drop='string' ]<br>
 146 [ --gof='string' ]<br>
 147 [ --logfile='string' ]<br>
 148 [ --model='string' ]<br>
 149 [ --p_backward='string' ]<br>
 150 [ --p_forward='string' ]<br>
 151 [ --search_direction='forward|backward|both' ]<br>
 152 [ --abort_on_fail ]<br>
 153 [ --clean ]<br>
 154 [ --compress ]<br>
 155 [ --cpu_time='integer' ]<br>
 156 [ --debug=0 ]<br>
 157 [ --debug_package='string' ]<br>
 158 [ --debug_subroutine='string' ]<br>
 159 [ --directory='string' ]<br>
 160 [ --extra_data_file='string' ]<br>
 161 [ --extra_files='string' ]<br>
 162 [ --grid_batch_size='integer' ]<br>
 163 [ --missing_data_token='string' ]<br>
 164 [ --nm_directory='string' ]<br>
 165 [ --nm_version='string' ]<br>
 166 [ --outputfile='string' ]<br>
 167 [ --picky ]<br>
 168 [ --remove_temp_files ]<br>
 169 [ --results_file='string' ]<br>
 170 [ --retries='integer' ]<br>
 171 [ --run_on_nordugrid ]<br>
 172 [ --seed='string' ]<br>
 173 [ --threads='integer' ]<br>
 174 [ --tweak_inits ]</p>
 175 <h3 class="heading1">Description</h3>
 176
 177 <p>The Stepwise Covariate Model (SCM) building tool of PsN implements
 178 Forward Selection and Backward Elimination of covariates to a
 179 model. In short, one model for each relevant parameter-covariate
 180 relationship is prepared and tested in a univariate manner. In the
 181 first step the model that gives the best fit of the data according to
 182 some criteria is retained and taken forward to the next step. In the
 183 following steps all remaining parameter-covariate combinations are
 184 tested until no more covariates meet the criteria for being included
 185 into the model. The Forward Selection can be followed by Backward
 186 Elimination, which proceeds as the Forward Selection but reversely,
 187 using stricter criteria for model improvement.</p>
 188
 189 <p>The Stepwise Covariate Model building procedure is run by the scm
 190 utility. The options to the scm utility are of three diffrent types,
 191 first are the common options which works like the common options for
 192 all tools. Then are the SCM specific command line options. And last
 193 are options which have a more complex structures and are considered to
 194 cumbersome to specify on the command line. These options must
 195 therefore be specified in a separate configuration file. It is
 196 possible to provide values for all options, including the common
 197 options, in the configuration file but it should be noted that the
 198 command line overrides the configuration file, if an option is
 199 specified at both locations. </p>
 200
 201 <h3 class="heading1">Command line options</h3>
 202 <p>
 203
 204 These are the non-composite options specific to the <span
 205 class="style2">scm</span> utility. Read the <a
 206 href="execute_docs.php">execute documentation</a> for a list of common
 207 options. The composite options are listed in the configuration file
 208 section. </p>
 209
 210 <dl>
 211
 212   <dt><b>config_file</b></dt>
 213   </dl>
 214 <p>A path and file name to a
 215   file to read configuration settings from.
 216     </p>
 217 <dl>
 218
 219   <dt><b>search_direction</b></dt>
 220   </dl>
 221 <p>Which search task to
 222       perform: backward, forward or both is allowed.
 223     </p>
 224 <dl>
 225
 226   <dt><b>logfile</b></dt>
 227   </dl>
 228 <p>The name of the logfile.
 229     </p>
 230 <dl>
 231
 232   <dt><b>model</b></dt>
 233   </dl>
 234 <p>The name of the basic model file, without any parameter-covariate relations included.</p>
 235 <dl>
 236
 237   <dt><b>p_forward</b></dt>
 238   </dl>
 239 <p>Using the p_forward option, you can specify the p-value to use for the forward selection.</p>
 240 <dl>
 241
 242   <dt><b>p_backward</b></dt>
 243   </dl>
 244 <p>Using the p_backward option, you can specify the p-value to use for the backward deletion.</p>
 245 <dl>
 246
 247    <dt><b>p_value</b></dt>
 248    </dl><p>Use this option to set the p_value for both forward and backward
 249     steps.</p>
 250
 251   <dt><b>do_not_drop</b></dt>
 252   </dl>
 253
 254 <p>Since the number of columns are restricted to 20 for NONMEM it is
 255 necessary to minimize the number of undropped columns. The scm utility
 256 uses the '=DROP' syntax of NONMEM to exclude the covariate columns
 257 that are not used. If some covariates are used in the PK or PRED code
 258 in the basic model you must list them using the do_not_drop option to
 259 prevent them from being dropped.</p>
 260 -->
 261 <h3 align="left" class="heading1">SCM configuration file options</h3>
 262
 263 <span class="heading2">General considerations</span>
 264
 265 <p>The syntax of the simple options is just the name of the option
 266 followed by the equal sign and a valid value for the option. For
 267 example:</p>
 268
 269 <p class="style2">retries=5</p>
 270 <p>This states that a maximum of 5 retries will be used in the executions. </p>
 271 Some options accept Perl code:
 272 <p><span class="style2">base_criteria_values={ 1 =&gt; ofv =&gt; -9571.234}</span> </p>
 273 Other take comma-separated lists:
 274 <p><span class="style2">continuous_covariates=AGE,WT,ALBU,BILI,AST,ALT,ALKP,POT,MAG,CA,NA,TOTP</span></p>
 275
 276 Some options don't accept a value on the command line. They set the
 277 behavior of the utility simply by being specified or not. In the
 278 configuration file these options need to be followed by 1 or a 0. A 1
 279 indicates that it is used and a 0 that it is not used.
 280
 281 <p class="style2">fix=1</p>
 282 You can place a comment anywhere in the file by prefixing the line with a semicolon:
 283 <p><span class="style2">;ask_if_fail=0</span></p>
 284 If an option is long you can break the line with a backslash, just a linebreak will NOT work:
 285 <p class="style2">categorical_covariates=SEX,ARR,SHD,NYHA,RACE,ALCO,SMOK,BETA,CGLY,LDIU,\<br>
 286   TDIU,CANT,ACE,NITR,ACOA,POTA,TWOC,TREA,TWOD,INDU,\<br>
 287   TUBS,ALQT,ANTP,ANTD,ANTM,ANTH,ANTB,SULP,ANT1,CLIA,\<br>
 288   CLIB,CLIC,CL3,CIME,METF,FENM,PROC,HEP1,HEP2,HEP3 </p>
 289
 290 <p class="heading2">Simple options</p>
 291
 292 The simple options are the SCM specific command line options and the
 293 command line options common to all PsN Utilties.
 294
 295 <p class="heading2">List options</p>
 296
 297 List options are options that take enumerations of values like the
 298 <span class="style2">categorical_covariates</span> option:
 299
 300 <p class="style2">categorical_covariates=SEX,ARR,SHD,NYHA,RAC<p>
 301
 302 The list options valid in the configuration file are:
 303
 304 <p class="style2">categorical_covariates</p>
 305
 306 The <span class="style2">categorical_covariates</span> list option is
 307 neccessary for the scm to know which type of NONMEM code to generate
 308 for the parameter covariate relation.
 309
 310 <p class="style2">continuous_covariates</p>
 311
 312 The <span class="style2">categorical_covariates</span> list option is
 313 neccessary for the scm to know which type of NONMEM code to generate
 314 for the parameter covariate relation.
 315
 316 <p class="style2">do_not_drop</p>
 317
 318 If the dataset used with the scm is to wide, scm will drop the data
 319 columns that correponds to covariate which is not used in a particular
 320 step. However, if you have used that covariate in code that is not
 321 affected by the scm, NONMEM will produce an error. Therefore it is
 322 neccessary for you to specify which those covariates are, using the
 323 <span class="style2">do_not_drop</span> list option.
 324
 325 <p class="style2">extra_files</p>
 326
 327 If you need some extraordinary file to be copied into the NONMEM
 328 execution directory, specify them with the <span
 329 class="style2">extra_files</span> list option.
 330
 331 <p class="heading2">Code options</p>
 332
 333 Code options are almost like a Simple option. With the difference that
 334 the right side is evaluted by the perl interpretor. If you don't
 335 understand the difference, it is probably not important. However, it
 336 is available for a reason. The SCM have hooks for custom goodness of
 337 fit functions. Those functions may need some special input data. And
 338 for flexibility, we allow that data to be just about anything, the
 339 side effect is that it becomes to complex for the configuration file
 340 structure. The solution is to allow options that are small Perl
 341 programs. Those options we refer to as code options.
 342
 343 <p class="style2">base_criteria_values</p>
 344
 345 The <span class="style2">base_criteria_values</span> overrides default
 346 criterias for the goodness of fit function used. The default goodness
 347 of fit function takes its base_criteria_value to be the ofv of the
 348 initial model. If you would like to change the base ofv to 400 you
 349 would write:
 350
 351 <pre>base_criteria_values= { 1 => { ofv => 400 } }</pre>
 352
 353 <p class="heading2">Composite options </p>
 354
 355 <p>The composite options can not be specified on the command line. An
 356 exception is the <span class="style2">extra_data_files</span> option
 357 which is valid for all utilities. A composite option section starts
 358 with an option header followed by a set of lines with a left side, an
 359 equal sign and a right side.  </p>
 360 <!--
 361 hash:
 362         $this -> {'ofv_backward'} = defined $parm{'ofv_backward'} ? $parm{'ofv_backward'} : {} unless defined $this -> {'ofv_backward'};
 363         $this -> {'ofv_change'} = defined $parm{'ofv_change'} ? $parm{'ofv_change'} : {} unless defined $this -> {'ofv_change'};
 364         $this -> {'ofv_forward'} = defined $parm{'ofv_forward'} ? $parm{'ofv_forward'} : {} unless defined $this -> {'ofv_forward'};
 365 -->
 366 <dl>
 367
 368   <dt><b>extra_data_files</b></dt>
 369
 370   <dd>The <span class="style2">-extra_data_files</span> option is used
 371       to specify files with extra data. As NONMEM only accepts 20
 372       columns, it is sometimes necessary to split data files. The left
 373       side of each line holds the extra data file name. The right side
 374       is a comma-separated list of the column headers.
 375     <p><span class="style2">[extra_data_files]<br>
 376       sub.dta=ID,GRP,AGE,SEX,ARR,SHD,NYHA,LVEF,WT,HT,RACE,ALCO,SMOK,BETA</span><br>
 377     </p>
 378   </dd>
 379
 380   <dt><b>test_relations</b></dt>
 381
 382   <dd><span class="style2">The -test_relations </span>option is used
 383       to specify what parameter-covariate relations the scm utility
 384       will test. The left side of each row is a parameter name and the
 385       right side is a comma separated list of covariates.
 386
 387     <p class="style2">[test_relations]<br>
 388       CL=AGE,SEX,ARR,SHD,NYHA,WT,RACE,ALCO,SMOK,BETA,\<br>
 389           ALBU,BILI,AST,ALT,ALKP,POT,MAG,CA,NA,TOTP, \<br>
 390           ANT1,CLIA,CLIB,CLIC,CL3,CIME,METF,PROC<br><br>
 391           V=SEX,WT,ALBU,TOTP,LDIU,TDIU,ACOA,SULP<br></p>
 392   </dd>
 393
 394   <dt><b>included_relations</b></dt>
 395
 396   <dd>If you want to start the search with some relations included you
 397       can add them to the <span
 398       class="style2">included_relations</span>.  The left side of each
 399       row holds the name of a parameter and the right side a list of
 400       covariates. For each covariate you can specify a relation
 401       state. The general syntax is <span class="style2">COV-X</span>
 402       where COV is you covariate and X is the state.  If the state is
 403       omitted it will be set to 2.
 404
 405     <p><span class="style2">[included_relations]<br>
 406       CL=TDIU-2,CLIA-2,SEX-2<br>
 407       V=WT,ACOA-2,SEX-3,TOTP</span><br>
 408     </p>
 409   </dd>
 410
 411   <dt><b>valid_states</b></dt>
 412
 413   <dd>You can specify what states you want the SCM to test. By default
 414       it tests three states. 1 - not included, 2 - linear, 3 -
 415       piecewise linear and 4 - exponential parameterization.  The
 416       valid states are specified for separately continuous and
 417       categorical covariates.
 418
 419     <p class="style2">[valid_states]<br>
 420           categorical=1,2<br>
 421           continuous=1,2,3</p>
 422   </dd>
 423
 424   <dt><b>code</b></dt>
 425
 426   <dd>If you are not satisfied with the state specific NONMEM code
 427       generated by the scm, you can overide it using the code
 428       option. It lets you specify code for specific parameters,
 429       specific paramater - covariate relations and even specific
 430       states. Each line under the <span class="style2">[code]</span>
 431       header defines code for one parameter - covariate - state
 432       relation. Like this:
 433
 434       <p class="style2">[code]<br>
 435           CL:WT-1=THETA(1)</p>
 436
 437       This will change the default code for state 1 of the CL - WT
 438       relation. You can also use wildcards to redefine the code for
 439       multiple relations:
 440
 441       <p class="style2">[code]<br>
 442           CL:*-1=THETA(1)</p>
 443
 444       In this example you will redefine the code for all covaritates
 445       in a relation with CL.
 446
 447       <p class="style2">[code]<br>
 448           *:*-1=THETA(1)</p>
 449
 450       This example will redefine the code for all relations in state
 451       1. Notice that you can not use a wildcard for the state.
 452       <p>
 453       Generally it is useful to include the parameter and/or the
 454       covariate in the code. So to make it possible when using
 455       wildcards you can use the generic variables PARM and COV which
 456       will be replaced with the parameter and covariate in question
 457       for the current relation.
 458
 459   </dd>
 460   <dt><b>lower_bounds, upper_bounds and inits</b></dt>
 461
 462   <dd>The inits and bounds option lets you set initial estimates for
 463       thetas introduced in the code and their corresponding bounds.  A
 464       hockeystick relation introduces two new thetas, so to set the
 465       thetas value and bounds for the CL - WT relation you would
 466       write:
 467
 468       <p class="style2">[lower_bounds]<br>
 469          CL:WT-2=0.1, 0.05</p>
 470
 471       <p class="style2">[upper_bounds]<br>
 472          CL:WT-2=0.3, 0.08</p>
 473
 474       <p class="style2">[inits]<br>
 475          CL:WT-2=0.15,0.07</p>
 476
 477       This would correspond to the following lines in a NONMEM modelfile:
 478
 479         <p class="style2">THETA(1) = 0.1,0.15,0.4<br>
 480           THETA(2) = 0.05,0.07,0.08</p>
 481
 482       Just like in the code option you can use wildcards. Notice that
 483       if you specify to few or to many values, those you exclude will
 484       be replaced by defaults and the extraneous will be ignored.
 485
 486    </dd>
 487
 488
 489 </dl>
 490
 491 <p></p>
 492 <h3 class="heading1">Output</h3>
 493 <h4>Result file</h4>
 494 Currently, the logfile is the best place to look for the results from the scm utility.
 495 <h4>&nbsp;</h4>
 496 <p></p>
 497 </div>
 498 <p align="justify">&nbsp;</p>
 499 </div>
 500 <table border="0" cellpadding="0" cellspacing="0" width="780">
 501   <tbody>
 502     <tr>
 503       <td height="600" width="780">
 504       <table border="0" cellpadding="0" cellspacing="0" width="780">
 505         <tbody>
 506           <tr>
 507             <td colspan="7" height="201" width="780"><img
 508  src="images/indexpane1_1_.jpg" name="" alt="" border="0" height="201"
 509  width="780"></td>
 510           </tr>
 511           <tr>
 512             <td height="46" width="26"><img
 513  src="images/indexpane1_2_.jpg" name="" alt="" border="0" height="46"
 514  width="26"></td>
 515             <td height="46" width="73"><a href="index.php"
 516  onmouseover="changeImages(/*CMP*/ 'object', /*URL*/ 'images/indexhomeov.jpg'); return true;"
 517  onmouseout="changeImages(/*CMP*/ 'object', /*URL*/ 'images/indexhome.jpg'); return true;"><img
 518  src="images/indexhome.jpg" name="object" alt="Home" border="0"
 519  height="46" width="73"></a></td>
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 526             <td height="46" width="15"><img
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 529             <td height="46" width="40"><img
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 532             <td height="46" width="590"><img
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 534  width="590"></td>
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 536           <tr>
 537             <td colspan="7" height="7" width="780"><img
 538  src="images/indexpane1_3_.jpg" name="" alt="" border="0" height="7"
 539  width="780"></td>
 540           </tr>
 541           <tr>
 542             <td height="46" width="26"><img
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 544  width="26"></td>
 545             <td colspan="5" height="46" width="164"><a href="docs.php"
 546  onmouseover="changeImages(/*CMP*/ 'object1', /*URL*/ 'images/indexdocumentationov.jpg'); return true;"
 547  onmouseout="changeImages(/*CMP*/ 'object1', /*URL*/ 'images/indexdocumentation.jpg'); return true;"><img
 548  src="images/indexdocumentation.jpg" name="object1" alt="Documentation"
 549  border="0" height="46" width="164"></a></td>
 550             <td height="46" width="590"><img
 551  src="images/indexpane7_4_.jpg" name="" alt="" border="0" height="46"
 552  width="590"></td>
 553           </tr>
 554           <tr>
 555             <td colspan="7" height="7" width="780"><img
 556  src="images/indexpane1_5_.jpg" name="" alt="" border="0" height="7"
 557  width="780"></td>
 558           </tr>
 559           <tr>
 560             <td height="46" width="26"><img
 561  src="images/indexpane1_6_.jpg" name="" alt="" border="0" height="46"
 562  width="26"></td>
 563             <td colspan="3" height="46" width="109"><a
 564  href="download.php"
 565  onmouseover="changeImages(/*CMP*/ 'object2', /*URL*/ 'images/indexdownloadov.jpg'); return true;"
 566  onmouseout="changeImages(/*CMP*/ 'object2', /*URL*/ 'images/indexdownload.jpg'); return true;"><img
 567  src="images/indexdownload.jpg" name="object2" alt="Download" border="0"
 568  height="46" width="109"></a></td>
 569             <td colspan="3" height="46" width="645"><img
 570  src="images/indexpane5_6_.jpg" name="" alt="" border="0" height="46"
 571  width="645"></td>
 572           </tr>
 573           <tr>
 574             <td colspan="7" height="7" width="780"><img
 575  src="images/indexpane1_7_.jpg" name="" alt="" border="0" height="7"
 576  width="780"></td>
 577           </tr>
 578           <tr>
 579             <td height="46" width="26"><img
 580  src="images/indexpane1_8_.jpg" name="" alt="" border="0" height="46"
 581  width="26"></td>
 582             <td colspan="2" height="46" width="84"><a href="buglist.php"
 583  onmouseover="changeImages(/*CMP*/ 'object3', /*URL*/ 'images/indexbuglistov.jpg'); return true;"
 584  onmouseout="changeImages(/*CMP*/ 'object3', /*URL*/ 'images/indexbuglist.jpg'); return true;"><img
 585  src="images/indexbuglist.jpg" name="object3" alt="Buglist" border="0"
 586  height="46" width="84"></a></td>
 587             <td colspan="4" height="46" width="670"><img
 588  src="images/indexpane4_8_.jpg" name="" alt="" border="0" height="46"
 589  width="670"></td>
 590           </tr>
 591           <tr>
 592             <td colspan="7" height="7" width="780"><img
 593  src="images/indexpane1_9_.jpg" name="" alt="" border="0" height="7"
 594  width="780"></td>
 595           </tr>
 596           <tr>
 597             <td height="46" width="26"><img
 598  src="images/indexpane1_10_.jpg" name="" alt="" border="0" height="46"
 599  width="26"></td>
 600             <td colspan="4" height="46" width="124"><a href="list.php"
 601  onmouseover="changeImages(/*CMP*/ 'object4', /*URL*/ 'images/indexmailing_listov.jpg'); return true;"
 602  onmouseout="changeImages(/*CMP*/ 'object4', /*URL*/ 'images/indexmailing_list.jpg'); return true;"><img
 603  src="images/indexmailing_list.jpg" name="object4" alt="Mailing List"
 604  border="0" height="46" width="124"></a></td>
 605             <td colspan="2" height="46" width="630"><img
 606  src="images/indexpane6_10_.jpg" name="" alt="" border="0" height="46"
 607  width="630"></td>
 608           </tr>
 609           <tr>
 610             <td colspan="7" height="141" width="780"><img
 611  src="images/indexpane1_11_.jpg" name="" alt="" border="0" height="141"
 612  width="780"></td>
 613           </tr>
 614         </tbody>
 615       </table>
 616       </td>
 617     </tr>
 618     <tr>
 619       <td><img src="images/is_single_pixel_gif.gif" alt="" height="1"
 620  width="780"></td>
 621     </tr>
 622   </tbody>
 623 </table>
 624 <!--Adobe(R) LiveMotion(TM) DataMap1.0 DO NOT EDIT
 625 end DataMap -->
 626 </body>
 627 </html>