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