v2.2.1

nlmixr2est 2.2.1

• Align with the possibility that linCmt sensitivities may not be
  present (like intel c++)

Bug fix

• focei cache needs to be based on the parameter order as well as
  the model information (#415)

What's Changed

• 415 nlmixr2est focei needs to cache based on thetaomega order by @mattfidler in #416

Full Changelog: v2.2.0...v2.2.1

v2.2.0

New Features

• Algebraic mu referencing has been implemented in nlme and saem.

• New estimation method "nlm" has been added to estimate population
  only likelihoods using stats::nlm and possibly return a
  standardized nlmixr2 fit.

• New estimation method "nls" has been added to estimate population
  only problems. This uses minpack.lm::nlsNM by default if
  present, or the stats::nls

• New estimation method "optim" has been added to estimate population
  only likelihoods. This uses stats::optim and returns a
  standardized nlmixr2 fit.

• New estimation method "nlminb" has been added to estimate population
  only likelihoods. This uses stats::nlminb and returns a
  standardized nlmixr2 fit.

• New estimation methods from the minqa package: "bobyqa", "uobyqa"
  and "newuoa" have been added to estimate population only
  likelihoods. These methods returns a standardized nlmixr2 fit.

• New estimation method "lbfgsb3c" to estimate population only
  likelihoods. This returns a standardized nlmixr2 fit.

• New estimation method "n1qn1" to estimate population only
  likelihoods. This returns a standardized nlmixr2 fit.

• Added new feature for vpcSim() where a minimum number of subjects
  are simulated from the model when trying to fill in ODEs that were
  not solved successfully. By default this is 10. This also
  works-around a bug when there is only one subject simulated and the
  data.frame has a slightly different output.

Breaking changes

• Removed fit$saemTransformedData since it isn't actually used in
  saem anymore (but will break anyone's code who is using it)

• Now the internal function .foceiPreProcessData() requires the
  rxode2 control rxControl() because some of the new steady state
  lag features need to translate the data differently based on
  rxControl() options.

Bug fixes

• Printing models with correlated omega values and omega values fixed
  to zero no longer fails (#359)

• Add back values for $parHistData (#368)

• This requires a new rxode2 which will fix multiple endpoint issues observed (#394)

• Manual back-transformed values in $parFixed are now displaying
  correctly and are calculated based on the confidence interval in the
  control instead of 95% confidence no matter what (#397)

Other changes

• An as.rxUi() method was added for fit models (#377)

What's Changed

• Add mu2 processing by @mattfidler in #354
• Fix #359 by @billdenney in #360
• Return fit without table if table step fails by @mattfidler in #364
• Fix 366 by @billdenney in #367
• Only keep $parHistData and calc $parHist and $parHistStacked by @mattfidler in #370
• Clarify keep argument to vpcSim() by @billdenney in #380
• Quieter compile by @billdenney in #381
• 376 make sure and test that fit$eta are non zero by @mattfidler in #383
• With a zero gradient always reset by @mattfidler in #384
• 387 sslag ettrans rxcontrol update by @mattfidler in #388
• 394 error drugmetabolite modeing after zero oder absorption by @mattfidler in #395
• V2.1.7 by @mattfidler in #396
• Fix for #397, needs test still by @mattfidler in #398
• add as.rxUi() method for fit objects by @billdenney in #378
• V2.1.8 by @mattfidler in #401
• 402 nlm by @mattfidler in #403
• 404 nls by @mattfidler in #405
• 406 optim by @mattfidler in #407
• Fix lbfgsb3c documentation by @mattfidler in #408
• Udf by @mattfidler in #409
• 411 cran requests by @mattfidler in #413

Full Changelog: v2.1.8...v2.2.0

v2.1.8

nlmixr2est 2.1.8

• Version bump and a minor documentation update (same as nlmixr2est
  2.1.7). This version bump is to simply allow correct binary linkage
  to rxode2 2.0.14. Otherwise nlmixr2 models will crash R.

nlmixr2est 2.1.7

• As requested by CRAN, remove Rvmmin

• Values in $parFixed for BSV without exponential transformation are now
  correctly shown (#366)

v2.1.7

• As requested by CRAN, remove Rvmmin

• Fix SD calculation typo (#366)

v2.1.6

Breaking changes

• Since rxode2 now allows simulation with omega having diagonal
  zero elements, $omega and $omegaR now reflects this information
  including the zero omega elements in the output. On the other hand,
  the other eta-information and standard error information for zero
  etas are still excluded in $phiR, $phiSE, $eta etc.

Bug fixes

• vpcSim() works when an eta value is fixed to 0 (#341)

• augPred() now consistently uses the simulation model (instead of
  the inner model used for CWRES calculation).

What's Changed

• Add mu ref fix by @mattfidler in #338
• Make addCwres() error clearer for model with no etas by @billdenney in #340
• Update documentation to link parts together (and some minor code formatting changes) by @billdenney in #345
• vpcSim works with etas set to 0 by @billdenney in #342
• Warn on time-varying covariate changes by @mattfidler in #349
• Adds documentation for the nlmixr2 object by @john-harrold in #351
• Aug pred fix by @mattfidler in #352

New Contributors

• @john-harrold made their first contribution in #351

Full Changelog: v2.1.5...v2.1.6

v2.1.5

• Add $fitMergeFull, $fitMergInner, $fitMergeLeft,
  $fitMergeRight as a complement to $dataMergeFull,
  $dataMergInner, $dataMergeLeft, $dataMergeRight. The fit
  variants prefer columns in the fit dataset instead of the original
  dataset. This is useful for goodness of fit plots with censoring
  since the DV in the fit simulates values under the ipred/residual
  assumption and will give more appropriate goodness of fits,
  otherwise these values are the limit of whatever censoring is
  applied

• Moved the mu reference fix for the split mu referenced model here
  (from babelmixr2)

What's Changed

• Add simulation method by @mattfidler in #333
• 335 for $datamerge family prefer fit object instead of original data by @mattfidler in #336

Full Changelog: v2.1.4...v2.1.5

v2.1.4

nlmixr2est 2.1.4

• Breaking change, now calculate condition number based on covariance
  and correlation, the names have changed to be more explicit.
  conditionNumber changed to conditionNumberCov and a new metric
  conditionNumberCor has been added.

• A bug in boundary value detection prevented automatic covariance calculation
  with FOCEi estimation (#318)

• Fix vpcSim so that it will be a bit more robust when it is
  difficult to simulate.

• A bug in model piping which did not allow models to be appended to was fixed
  (rxode2#364)

• An internal change was made in nlmixr2.rxUi() to better support the
  babelmixr2 PKNCA estimation method (babelmixr2#75)

• Fixed bug where $iniUi did not return the initial ui when running
  non focei related methods. Also added alias of $uiIni to the
  same function.

• Dropped Stan headers for this package, also updated to C++17

What's Changed

• 289 issue in obtaining model estimates by @mattfidler in #290
• Fix rxode2 #364 by @billdenney in #292
• Remove debugging statement by @billdenney in #299
• Make some focei methods for simulation that are closer to est model by @mattfidler in #308
• 302 mu reference definition isnt correct for non mu referenced model by @mattfidler in #304
• Fallback to old method by @mattfidler in #310
• drop stan headers and eigen by @mattfidler in #319
• 318 fix bound by @billdenney in #321
• Make package installation consistent; fix typos; use label() by @billdenney in #325
• Speed up some testing by minimizing the fit iterations by @billdenney in #324
• Allow for babelmixr2::pkncaControl() not to set genRxControl by @billdenney in #326
• 311 condition numbers by @mattfidler in #323
• 316 wrong initial values in nlmixr2 object by @mattfidler in #322
• Rebuild documentation by @billdenney in #329

Full Changelog: v2.1.3...v2.1.4

v2.1.3

nlmixr2est 2.1.3

• Allows $etaH and related family to be integrated into a saem fit
  if cwres is calculated.

• Fixed a bug where nlmixrLlikObs in the merged dataset is sometimes
  named llikObs, now it is always named nlmixrLlikObs

• Fixed a bug where nlmixrLlikObs shows up in merged dataset when
  cwres is not calculated (it was always 0), also allow cwres
  calculation to pick up nlmixrLlikObs in merged dataset.

• Dropped dparser dependency

What's Changed

• 282 $etah not available for saem needs cwres but doesnt pull over standard errors by @mattfidler in #283
• 284 include log likelihood per observation when adding cwres by @mattfidler in #285
• Test nonmu and add test case for merge (and unsuccesful merge) by @mattfidler in #288

Full Changelog: https://github.com/nlmixr2/nlmixr2est/compare/v2.1.2...v2.1.3###

v2.1.2

nlmixr2est 2.1.2

• Fixes $etaH memory corruption so the standard errors of etas are now correct

• Removed the memory requirements for focei by neta*neta*nsub

• Fixed character based covariates so the work correctly (again) with
  focei. Added a test for this as well.

What's Changed

• Update installation instructions by @billdenney in #265
• Fix $etaH by @mattfidler in #269
• Update CI workflow to current versions by @billdenney in #275
• Update ci by @billdenney in #279
• Start testing bill's example by @mattfidler in #278
• Fuzzy bad, silver good by @mattfidler in #281
• Add ARMA_64BIT_WORD by @mattfidler in #277

Full Changelog: v2.1.0...v2.1.2

v2.1.0

nlmixr2est 2.1.0

Breaking changes

FOCEi

• Gill forward differences will not repeat now (by default), You can
  change back to prior behavior with foceiControl(repeatGillMax=3)

• Number of sticky recalculation is reduced to 4; to have the old
  behavior use foceiControl(stickyRecalcN=5)

• n2ll has been changed to ll to specify individual
  log-likelihoods. This was only used in simulation and was not well
  documented.

• Generalized log-likelihood is only supported with rxode2 2.0.8 or later.

FOCEi covariance calculation

• The S matrix calculation was made a bit more robust to errors in
  individual gradients. When there are errors in the individual
  gradient calculation, assume the gradient is the same as the
  overall gradient. In the tests cases, were reasonable using this
  adjusted S matrix. This means if some individuals do not have very
  much data to support a specific parameter, a S matrix calculation
  for the population will still be generated. When there is some
  patients/subject combinations that do not have sufficient data, we
  will add the following to the run information: S matrix had problems solving for some subject and parameters. The S matrix
  calculation will still fail if the percentage of parameters that
  are being reset is lower than foceiControl(smatPer=0.6) or
  whatever you specify.

• The r,s covariance matrix will now also check for unreasonably
  small values (controlled by foceiControl(covSmall=...)) and
  select a different covariance estimate method even when the "r" and
  "s" matrices are calculated "correctly".

New features

• What type(s) censoring (if any) is now stored in fit$censInformation

• Standard errors of $etas can now be obtained with fit$phiSE,
  also available are fit$phiRSE (relative standard error),
  fit$phiH, (individual hessian), fit$phiC (individual
  covariances), fit$phiR (individual correlation matrices)

• Can also use Shi 2021 differences in addition to Gill differences.
  In our tests (using the same datasets as CPT) these produced worse
  estimates than the Gill 1983, though it is unclear why since it
  should be a faster more accurate method. A modified version is used
  in calculating the individual Hessians of numerically for the
  generalized likelihood approach.

• Generalized likelihood estimation is now present in nlmixr2est for
  focei, foce and posthoc

• nmNearPD() is a function you may use for nearest positive definite
  matrix. This is derived from Matrix::nearPD() but is implemented
  in C/C++ to be used in (possibly threaded) optimization.

• Individual Hessians can be accessed by $phiH, covariance by
  $phiC, eta standard errors by $phiSE and eta RSEs can be
  accessed by $phiRSE. There are eta aliases for these as well
  ($etaH, $etaC, $etaSE, and $etaRSE).

• Can now access the individual point's contribution to the overall
  likelihood when merging to the original dataset. These merges can be
  accessed with $dataMergeFull, $dataMergeLeft, $dataMergeRight,
  and $dataMergeInner. The columns with the individual data column
  is nlmixrLlikObs.

  To calculate the total focei/foce objective function, the sum of the
  likelihoods still need to be adjusted by the omega/eta contribution,
  and the individual Hessians, and possibly the NONMEM objective
  function offset constant.

Censoring fixes

• Fixed bug where datasets with censoring that are not lower case cens and limit do not
  produce the correct table output (#180)

FOCEi updates

• Resets now scale properly when a value is simulated outside the limit
• Models with zero gradients on the first step now switch to bobyqa
  by default. With this, it is more important to examine the model
  parameters and fits for plausibility.

What's Changed

• 179 m4 method simulations may be off by @mattfidler in #182
• 151 when i just tried to simulate from my model and data i got the below errors im digging deeper to try to figure out what is the matter by @mattfidler in #187
• Add a different stop so that it gives a bit more information when it … by @mattfidler in #191
• Llik focei by @mattfidler in #188
• 184 feature request move $warnings to $runinfo or something similar and dont warn by @mattfidler in #193
• 200 rcpparmadillo 2 by @mattfidler in #203
• 205 function rxgt is not supported in rxode2 by @mattfidler in #206
• Print out every time by @mattfidler in #207
• Add $dataLloq and $dataUloq to fit by @mattfidler in #212
• Keep vpcSim the same if it is normally related items by @mattfidler in #209
• Fix simulation to support dvid() and models without dvid()/cmt() by @mattfidler in #214
• Fix for vpc sim by @mattfidler in #216
• Fall back to length normalization type by @mattfidler in #219
• 217 rse focei less stable than last release by @mattfidler in #220
• Make sure the etas are fixed with the output by @mattfidler in #224
• 199 running a model changes the source object by @mattfidler in #204
• 226 restart error by @mattfidler in #227
• 228 preds seem wrong when mixing normal log likelihood and non normal log likelihood by @mattfidler in #229
• Now test pred, ipred; pred fails by @mattfidler in #230
• Start splitting out depending on what is available with rxode2 by @mattfidler in #232
• Address issues for nlmixr2est by @mattfidler in #234
• Add new CRAN submission tag by @mattfidler in #235
• Fix split model by @mattfidler in #237
• Add some split testing by @mattfidler in #239
• Check for environment a bit more stricter by @mattfidler in #242
• Handle edge cases for NA predictions by @mattfidler in #243
• Env is compressed by @mattfidler in #245
• 246 nlmixr2est with rxode2parse by @mattfidler in #247
• 246 nlmixr2est with rxode2parse by @mattfidler in #248
• 250 rxode2random by @mattfidler in #251
• 252 use rxode2et by @mattfidler in #253
• Fix and test for non mu-referenced model by @mattfidler in #259
• Make table integration more robust by @billdenney in #256
• Make .foceiPreProcessData() work with tibbles by @billdenney in #262

Full Changelog: v2.0.8...v2.1.0