sim_test: Bootstrap test for the assessment of similarity of drug...

In SimDissolution: Modeling and Assessing Similarity of Drug Dissolutions Profiles

Description

Function for testing whether two dissolution profiles are similar concerning the hypotheses H_0: \max_{t\in\mathcal{T}} |m_1(t,β_1)-m_2(t,β_2)|≥q ε\ vs.\ H_1: \max_{t\in\mathcal{T}} |m_1(t,β_1)-m_2(t,β_2)|< ε.

$m_1$ and $m_2$ are pharmacokinetic models chosen from a candidate set containing a First order, Hixson-Crowell,Higuchi, Weibull and a logistic model.

See Moellenhoff et al. (2018) <doi:10.1002/sim.7689> for details.

Usage

sim_test(time1, time2 = time1, conc1, conc2, m1, m2, epsilon = 10,
  B = 1000, plot = FALSE)

Arguments

time1, time2	vectors containing the time points of measurements for each of the two formulations; if not further specified the time points are identical in both groups
conc1, conc2	data frames or matrices containing the concentrations obtained for each of the two formulations (see the example)
m1, m2	model types. Built-in models are "firstorder", "hixson", "higuchi", "weibull" and "logistic"
epsilon	positive argument specifying the equivalence threshold (in %), default is 10% corresponding to an f2 of 50 according to current guidelines
B	number of bootstrap replications. If missing, default value of B is 1000
plot	if TRUE, a plot of the absolute difference curve of the two estimated models will be given. The default is FALSE.

Value

A list containing the p.value, the types of models, the f2, the maximum absolute difference of the models, the estimated model parameters, the number of bootstrap replications and a summary of the bootstrap test statistic. Furthermore plots of the two models are given.

References

Moellenhoff et al. (2018) <doi:10.1002/sim.7689>

EMA (2010) <https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf>

Examples

data(example_data)
conc1 <- select(filter(example_data,Group=="1"),-Tablet,-Group)
conc2 <- select(filter(example_data,Group=="2"),-Tablet,-Group)
time <- c(10,15,20,30,45,60)
sim_test(time1=time,time2=time,conc1=conc1,conc2=conc2,m1="logistic",m2="logistic",B=500,plot=TRUE)

Example output

Loading required package: dplyr

Attaching package: ‘dplyr’

The following objects are masked from ‘package:stats’:

    filter, lag

The following objects are masked from ‘package:base’:

    intersect, setdiff, setequal, union

Loading required package: alabama
Loading required package: numDeriv
Loading required package: mvtnorm
$p.value
[1] 0.092

$types.of.models
[1] "Logistic" "Logistic"

$max.abs.difference
[1] 7.287205

$f2
[1] 70.88722

$estimated.model.param.
[1] -4.049402  1.885921 -5.318727  2.309687

$bootstrap.replications
[1] 500

$summary.boot
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
  4.728   8.638  10.134  10.154  11.575  17.209 

SimDissolution documentation built on Sept. 27, 2019, 5:03 p.m.