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pla (version 0.2)

pla-package: Parallel Line Assays

Description

Parallel Line Models:

Completely Randomized Design, Randomized Block Design, and Latin Squares Design.

Balanced data are fitted as described in the Ph.Eur.

In the presence of missing values complete data analysis can be performed (with computation of Fieller's confidence intervals for the estimated potency), or imputation of values can be applied.

The package contains a script such that a pdf-document with a report of an analysis of an assay can be produced from an input file with data of the assay just by entering the name of the input-file. Here no knowledge of R is needed by the user. This tool requires R and Tex (e.g. MikTex) to be installed. The .BAT- and .csh-files for this is found in .../pla/scripts/ of your installed pla package. You can of course modify the "skeleton" (.../pla/scripts/Skeleton/Skeleton-xtable.Rnw) Sweave program of this script. You should not (only) place your data in .../pla/scripts/data, but copy the content of the directory .../pla/scripts/ to some place not effected by updates of R and the pla-package.

Arguments

Details

Package:
pla
Type:
Package
Version:
0.2
Date:
2015-09-09
License:
GPL (>= 2)

Contents:

  • pla: Functions for defining and creating parallel line assay models. Imputation of missing values is performed, as an option.
  • pla.fit or fit on pla-model: Estimation in parallel line models, with listing of results.
    • pheur325: Estimation of potency and confidence limits as described at page 480 in the Ph.Eur.
  • pla.plots or plot on pla-model: Make plots for parallel line models.
    • plotSamples: One scatter plot for parallel line models.
    • jitterSteps: Compute a perturbed version of the concentration-variable.
  • Examples from Ph.Eur.:
    • 5.1.1. Two-dose multiple assay with completely randomized design; An assay of corticotrophin by subcutaneous injection in rats: Corticotrophin
    • 5.1.2. Three-dose latin square design; Antibiotic agar diffusion assay using a rectangular tray: AgarDiffusionAssay.
    • 5.1.3. Four-dose randomized block design; Antibiotic turbidimetric assay: Turbidimetric.
    • 5.1.4. Five-dose multiple assay with completely randomized design; An in-vitro assay of three hepatitis B vaccines against a standard: HepatitisB.
  • From CombiStats - EDQM, Council of Europe http://combistats.edqm.eu:
    • Example 1 - Three-dose parallel line assay; completely randomized; square transformation; explicit volume units; Diphteria,
    • Example 2 - Three-dose parallel line assay; randomized block; explicit content notation; Erythropoietin,
    • Example 3 - Four-dose parallel line assay; completely randomized; logarithmic transformation; explicit ratio notation; FactorIX,
    • Example 5 - Three-dose parallel line assay; completely randomized; custom transformation; explicit content notation; HeparinSodium,
    • Example 7 - Five-dose parallel line assay; completely randomized; logarithmic transformation; explicit ratio notation; HepatitisBvaccine,
    • Example 8 - Four-dose parallel line assay; completely randomized; square root transformation; explicit content notation; HumanHepatitis (Human Hepatitis A immunoglobulin),
    • Example 10 - Four-dose parallel line assay; completely randomized; logarithmic transformation; explicit ratio notation; IPV (Inactivated Poliomyelitis Vaccine).
    • Example 15 - Five-dose multiple assay; randomized block design; explicit ratio notation Nystatin,
    • Example 22 - Three-dose parallel line assay at three independent occasions; randomized block; symbolic notation; Erythromycin,
  • Other example: Vancomycin.
  • The two main functions are pla.fit and pla.plots, which expects data in the format as returned by assayTable2frame or data2assayFrame. But the function readAssayTable is also very useful.

    One way to understand (and to reproduce) the structure of the expected input of pla.fit and pla.plots is to look into data2assayFrame and AgarDiffusionAssay. The column names Response, Dilution, Sample, Replicate, Row, and Column of the input for data2assayFrame cannot be changed. Row and Column are used for "Latin squares".

    Replicate is used for "blocks" and completely random designs.

    pheur325 is designed to be called from pla.fit, and plotSamples is designed to be called from pla.plots.

    The input dataframe for pla.plots and pla.fit should be ordered by Sample and "DilutionStep".

    The output listing is designed for "R CMD Sweave" and "pdflatex".

    Acknowledgment: Thanks to CombiStats for permitting the presentation of the data of CombiStats in this package. The statistical analyses of this data are also performed by the CombiStats program, and the results can be found on http://combistats.edqm.eu/.

    References

    Ph.Eur.: Chapter 5.3. Statistical analysis. In EUROPEAN PHARMACOPOEIA version 8.0, 2014; 607--635 (475-504 in version 5.0, 2004).

    Coward, Katrine Hope, Kassner, Elsie Woodward (1941): A Comparison between Interlitter and Intralitter variation in rats with respect to the healing of rachitic bones by vitamin D. Pharmaceutical Society, London. Fieller, E.C.: The biological standardization of insulin. Supplement to the Journal of the Royal Statistical Society. 1940; Vol. VII., No. 1. Bliss, C.I. (1952): The Statistics of Bioassay - with special reference to the vitamin. Academic Press, New York.

    Arthur Linder, Genova, Switzerland (1964): Statistics of Bioassays, Notes on lectures held during the spring semester (1964) at the Statistics Department, University of North Carolina, Chapel Hill, N. C.

    Finney, David J. (1978): Statistical Method in Biological Assay. Charles Griffin & Company Ltd. Third Edition.

    Examples

    Run this code
    data(Corticotrophin); Data <- Corticotrophin
    
    Design <- "crd"
    Data <- readAssayTable(paste(system.file(package = "pla"),
                                 "vignettes/PhEur/data/Corticotrophin.txt",
                                 sep = "/"))
    Frame  <- as.data.frame(Data)
    fits <- pla.fit(Frame, design = Design, sampleLabels = c("S", "T", "U"),
                    dr = 4, returnPotencyEstimates = TRUE)
    plots <- pla.plots(Frame, design = Design, sampleLabels = c("S", "T", "U"), 
                       colTst = c("blue", "red"), showRho = FALSE,
                       main = "PhEur: Corticotrophin; Subcutaneous Injection In Rats",
                       tests = fits@tests,)
    
    ## Alternative on object of class 'pla':
    plaModel <- plaCRD(Data,
                       assayTitle = "PhEur: Corticotrophin; Subcutaneous Injection In Rats")
    Fits <- fit(plaModel)
    

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