Control for bobyqa estimation method in nlmixr2

Usage

bobyqaControl(
  npt = NULL,
  rhobeg = NULL,
  rhoend = NULL,
  iprint = 0L,
  maxfun = 100000L,
  returnBobyqa = FALSE,
  stickyRecalcN = 4,
  maxOdeRecalc = 5,
  odeRecalcFactor = 10^(0.5),
  useColor = crayon::has_color(),
  printNcol = floor((getOption("width") - 23)/12),
  print = 1L,
  normType = c("rescale2", "mean", "rescale", "std", "len", "constant"),
  scaleType = c("nlmixr2", "norm", "mult", "multAdd"),
  scaleCmax = 1e+05,
  scaleCmin = 1e-05,
  scaleC = NULL,
  scaleTo = 1,
  rxControl = NULL,
  optExpression = TRUE,
  sumProd = FALSE,
  literalFix = TRUE,
  addProp = c("combined2", "combined1"),
  calcTables = TRUE,
  compress = TRUE,
  covMethod = c("r", ""),
  adjObf = TRUE,
  ci = 0.95,
  sigdig = 4,
  sigdigTable = NULL,
  ...
)

Arguments

npt

The number of points used to approximate the objective function via a quadratic approximation. The value of npt must be in the interval [n+2,(n+1)(n+2)/2] where n is the number of parameters in `par`. Choices that exceed 2*n+1 are not recommended. If not defined, it will be set to min(n * 2, n+2).

rhobeg

`rhobeg` and `rhoend` must be set to the initial and final values of a trust region radius, so both must be positive with `0 < rhoend < rhobeg`. Typically `rhobeg` should be about one tenth of the greatest expected change to a variable. If the user does not provide a value, this will be set to `min(0.95, 0.2 * max(abs(par)))`. Note also that smallest difference `abs(upper-lower)` should be greater than or equal to `rhobeg*2`. If this is not the case then `rhobeg` will be adjusted.

rhoend

The smallest value of the trust region radius that is allowed. If not defined, then 1e-6 times the value set for `rhobeg` will be used.

iprint

The value of `iprint` should be set to an integer value in `0, 1, 2, 3, ...`, which controls the amount of printing. Specifically, there is no output if `iprint=0` and there is output only at the start and the return if `iprint=1`. Otherwise, each new value of `rho` is printed, with the best vector of variables so far and the corresponding value of the objective function. Further, each new value of the objective function with its variables are output if `iprint=3`. If `iprint > 3`, the objective function value and corresponding variables are output every `iprint` evaluations. Default value is `0`.

maxfun

The maximum allowed number of function evaluations. If this is exceeded, the method will terminate.

returnBobyqa

return the bobyqa output instead of the nlmixr2 fit

stickyRecalcN

The number of bad ODE solves before reducing the atol/rtol for the rest of the problem.

maxOdeRecalc

Maximum number of times to reduce the ODE tolerances and try to resolve the system if there was a bad ODE solve.

odeRecalcFactor

The ODE recalculation factor when ODE solving goes bad, this is the factor the rtol/atol is reduced

useColor

Boolean indicating if focei can use ASCII color codes

printNcol

Number of columns to printout before wrapping parameter estimates/gradient

print

Integer representing when the outer step is printed. When this is 0 or do not print the iterations. 1 is print every function evaluation (default), 5 is print every 5 evaluations.

normType

This is the type of parameter normalization/scaling used to get the scaled initial values for nlmixr2. These are used with scaleType of.

With the exception of rescale2, these come from Feature Scaling. The rescale2 The rescaling is the same type described in the OptdesX software manual.

In general, all all scaling formula can be described by:

$$v_{scaled}$$ = ($$v_{unscaled}-C_{1}$$)/$$C_{2}$$

Where

The other data normalization approaches follow the following formula

$$v_{scaled}$$ = ($$v_{unscaled}-C_{1}$$)/$$C_{2}$$

rescale2 This scales all parameters from (-1 to 1). The relative differences between the parameters are preserved with this approach and the constants are:

$$C_{1}$$ = (max(all unscaled values)+min(all unscaled values))/2

$$C_{2}$$ = (max(all unscaled values) - min(all unscaled values))/2
rescale or min-max normalization. This rescales all parameters from (0 to 1). As in the rescale2 the relative differences are preserved. In this approach:

$$C_{1}$$ = min(all unscaled values)

$$C_{2}$$ = max(all unscaled values) - min(all unscaled values)
mean or mean normalization. This rescales to center the parameters around the mean but the parameters are from 0 to 1. In this approach:

$$C_{1}$$ = mean(all unscaled values)

$$C_{2}$$ = max(all unscaled values) - min(all unscaled values)
std or standardization. This standardizes by the mean and standard deviation. In this approach:

$$C_{1}$$ = mean(all unscaled values)

$$C_{2}$$ = sd(all unscaled values)
len or unit length scaling. This scales the parameters to the unit length. For this approach we use the Euclidean length, that is:

$$C_{1}$$ = 0

$$C_{2}$$ = $$\sqrt(v_1^2 + v_2^2 + \cdots + v_n^2)$$
constant which does not perform data normalization. That is

$$C_{1}$$ = 0

$$C_{2}$$ = 1

scaleType

The scaling scheme for nlmixr2. The supported types are:

nlmixr2 In this approach the scaling is performed by the following equation:

$$v_{scaled}$$ = ($$v_{current} - v_{init}$$)*scaleC[i] + scaleTo

The scaleTo parameter is specified by the normType, and the scales are specified by scaleC.
norm This approach uses the simple scaling provided by the normType argument.
mult This approach does not use the data normalization provided by normType, but rather uses multiplicative scaling to a constant provided by the scaleTo argument.

In this case:

$$v_{scaled}$$ = $$v_{current}$$/$$v_{init}$$*scaleTo
multAdd This approach changes the scaling based on the parameter being specified. If a parameter is defined in an exponential block (ie exp(theta)), then it is scaled on a linearly, that is:

$$v_{scaled}$$ = ($$v_{current}-v_{init}$$) + scaleTo

Otherwise the parameter is scaled multiplicatively.

$$v_{scaled}$$ = $$v_{current}$$/$$v_{init}$$*scaleTo

scaleCmax

Maximum value of the scaleC to prevent overflow.

scaleCmin

Minimum value of the scaleC to prevent underflow.

scaleC

The scaling constant used with scaleType=nlmixr2. When not specified, it is based on the type of parameter that is estimated. The idea is to keep the derivatives similar on a log scale to have similar gradient sizes. Hence parameters like log(exp(theta)) would have a scaling factor of 1 and log(theta) would have a scaling factor of ini_value (to scale by 1/value; ie d/dt(log(ini_value)) = 1/ini_value or scaleC=ini_value)

For parameters in an exponential (ie exp(theta)) or parameters specifying powers, boxCox or yeoJohnson transformations , this is 1.
For additive, proportional, lognormal error structures, these are given by 0.5*abs(initial_estimate)
Factorials are scaled by abs(1/digamma(initial_estimate+1))
parameters in a log scale (ie log(theta)) are transformed by log(abs(initial_estimate))*abs(initial_estimate)

These parameter scaling coefficients are chose to try to keep similar slopes among parameters. That is they all follow the slopes approximately on a log-scale.

While these are chosen in a logical manner, they may not always apply. You can specify each parameters scaling factor by this parameter if you wish.

scaleTo

Scale the initial parameter estimate to this value. By default this is 1. When zero or below, no scaling is performed.

rxControl

`rxode2` ODE solving options during fitting, created with `rxControl()`

optExpression

Optimize the rxode2 expression to speed up calculation. By default this is turned on.

sumProd

Is a boolean indicating if the model should change multiplication to high precision multiplication and sums to high precision sums using the PreciseSums package. By default this is FALSE.

literalFix

boolean, substitute fixed population values as literals and re-adjust ui and parameter estimates after optimization; Default is `TRUE`.

addProp

specifies the type of additive plus proportional errors, the one where standard deviations add (combined1) or the type where the variances add (combined2).

The combined1 error type can be described by the following equation:

$$y = f + (a + b\times f^c) \times \varepsilon$$

The combined2 error model can be described by the following equation:

$$y = f + \sqrt{a^2 + b^2\times f^{2\times c}} \times \varepsilon$$

Where:

- y represents the observed value

- f represents the predicted value

- a is the additive standard deviation

- b is the proportional/power standard deviation

- c is the power exponent (in the proportional case c=1)

calcTables

This boolean is to determine if the foceiFit will calculate tables. By default this is TRUE

compress

Should the object have compressed items

covMethod

Method for calculating covariance. In this discussion, R is the Hessian matrix of the objective function. The S matrix is the sum of individual gradient cross-product (evaluated at the individual empirical Bayes estimates).

"r,s" Uses the sandwich matrix to calculate the covariance, that is: solve(R) %*% S %*% solve(R)
"r" Uses the Hessian matrix to calculate the covariance as 2 %*% solve(R)
"s" Uses the cross-product matrix to calculate the covariance as 4 %*% solve(S)
"" Does not calculate the covariance step.

adjObf

is a boolean to indicate if the objective function should be adjusted to be closer to NONMEM's default objective function. By default this is TRUE

ci

Confidence level for some tables. By default this is 0.95 or 95% confidence.

sigdig

Optimization significant digits. This controls:

The tolerance of the inner and outer optimization is 10^-sigdig
The tolerance of the ODE solvers is 0.5*10^(-sigdig-2); For the sensitivity equations and steady-state solutions the default is 0.5*10^(-sigdig-1.5) (sensitivity changes only applicable for liblsoda)
The tolerance of the boundary check is 5 * 10 ^ (-sigdig + 1)

sigdigTable

Significant digits in the final output table. If not specified, then it matches the significant digits in the `sigdig` optimization algorithm. If `sigdig` is NULL, use 3.

...

Additional arguments passed to nlmixr2est::bobyqaControl().

Value

bobqya control structure

Author

Matthew L. Fidler

Examples

# \donttest{
# A logit regression example with emax model

dsn <- data.frame(i=1:1000)
dsn$time <- exp(rnorm(1000))
dsn$DV=rbinom(1000,1,exp(-1+dsn$time)/(1+exp(-1+dsn$time)))

mod <- function() {
 ini({
   E0 <- 0.5
   Em <- 0.5
   E50 <- 2
   g <- fix(2)
 })
 model({
   v <- E0+Em*time^g/(E50^g+time^g)
   ll(bin) ~ DV * v - log(1 + exp(v))
 })
}

fit2 <- nlmixr(mod, dsn, est="bobyqa")
#>  
#>  
#>  
#>  
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → pruning branches (`if`/`else`) of population log-likelihood model...
#> ✔ done
#> → loading llik model into symengine environment...
#> → finding duplicate expressions in population log-likelihood model...
#> → optimizing duplicate expressions in population log-likelihood model...
#> ✔ done
#>  
#>  
#> using C compiler: ‘gcc (Ubuntu 11.4.0-1ubuntu1~22.04) 11.4.0’
#> → calculating covariance
#> ✔ done
#> → loading into symengine environment...
#> → pruning branches (`if`/`else`) of full model...
#> ✔ done
#> → finding duplicate expressions in EBE model...
#> → optimizing duplicate expressions in EBE model...
#> → compiling EBE model...
#>  
#>  
#> using C compiler: ‘gcc (Ubuntu 11.4.0-1ubuntu1~22.04) 11.4.0’
#> ✔ done
#> → Calculating residuals/tables
#> ✔ done
#> → compress origData in nlmixr2 object, save 9096
#> → compress parHistData in nlmixr2 object, save 15552

print(fit2)
#> ── nlmixr² log-likelihood bobyqa ──
#> 
#>           OBJF      AIC      BIC Log-likelihood Condition#(Cov) Condition#(Cor)
#> lPop -681.2477 1162.629 1177.353      -578.3147        197.8405        48.07442
#> 
#> ── Time (sec $time): ──
#> 
#>            setup table compress    other
#> elapsed 0.004205 0.049    0.011 2.578795
#> 
#> ── ($parFixed or $parFixedDf): ──
#> 
#>        Est.     SE  %RSE   Back-transformed(95%CI) BSV(SD) Shrink(SD)%
#> E0  -0.7442 0.2571 34.54 -0.7442 (-1.248, -0.2404)                    
#> Em    4.627  1.575 34.04       4.627 (1.54, 7.714)                    
#> E50   2.376 0.9338  39.3     2.376 (0.5458, 4.206)                    
#> g         2  FIXED FIXED                         2                    
#>  
#>   Covariance Type ($covMethod): r
#>   Censoring ($censInformation): No censoring
#> 
#> ── Fit Data (object is a modified tibble): ──
#> # A tibble: 1,000 × 5
#>   ID      TIME    DV  IPRED      v
#>   <fct>  <dbl> <dbl>  <dbl>  <dbl>
#> 1 1     0.0304     1 -1.13  -0.743
#> 2 1     0.0320     0 -0.389 -0.743
#> 3 1     0.0329     0 -0.389 -0.743
#> # ℹ 997 more rows

# you can also get the nlm output with

fit2$bobyqa
#> parameter estimates: -0.744249036396639, 4.62703353089203, 2.37602005800094 
#> objective: 578.314687574017 
#> number of function evaluations: 238 

# The nlm control has been modified slightly to include
# extra components and name the parameters
# }