bootf2BCA Files

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bootf2BCA v1.3.3
Author: Prof. dr hab. Aleksander Mendyk
Chair of Pharmaceutical Technology and Biopharmaceutics
Faculty of Pharmacy
Jagiellonian University-Medical College
Medyczna 9 St
30-688 Kraków, Poland
phone: +48-12-6205-601
e-mail: mfmendyk@cyf-kr.edu.pl, aleksander.mendyk.pl@gmail.com
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bootf2BCA is a software for for estimation of confidence interval for f2 an FDA's similarity factor. Boostrap estimation is performed and among the other types a BC(alpha) confidence interval is calculated to provide ability to use f2 in cases of large variation in dissolution data, namely RSD > 10(20)%

1. Requirements:

R environment (https://www.r-project.org/) with additional packages installed: boot (https://cran.r-project.org/web/packages/boot/index.html). For GUI more packages are needed: shiny (https://cran.r-project.org/package=shiny),shinyFiles (https://cran.r-project.org/package=shinyFiles), plotly (https://cran.r-project.org/package=plotly)

Any modern operating system capable of handling R environment: Windows, Linux, MacOS

2. How to run
For command line interface go to subdirectory CLI and simply run the script bootf2BCA_v1.3.3.R interactively or non-interactively with your R environment. The script logs all relevant data into the report file that is a txt file suitable for importing to the spreadsheet like i.e. Excel or Calc. For GUI switch to GUI directory and run shiny application via run_shiny.R script

3. Run parameters

3A. Input data
Two files are required to perform calculations: reference and test file representing as per FDA terminology the dissolution results of reference and test formulation respectively. These files are tab-delimited with each dissolution profile represented in a separate column, where the first column is a time axis. No labels are provided in this file, neither for columns nor for rows. The dissolution results are expressed as percentages of the label claim
An example of such file is presented below and additionally ref.txt and test.txt files are available in the root directory for testing purposes

30	36.1	33	35.7	32.1	36.1	34.1	32.4	39.6	34.5	38	32.2	35.2
60	58.6	59.5	62.3	62.3	53.6	63.2	61.3	61.8	58	59.2	56.2	58
90	80	80.8	83	81.3	72.6	83	80	80.4	76.9	79.3	77.2	76.7
180	93.3	95.7	97.1	92.8	88.8	97.4	96.8	98.6	93.3	94	96.3	96.8

3B.Script parameters

Running parameters of the script are controlled via its head section with following variables. The default settings are provided for quick start

input_file_test_sample
This variable provides name of the input file for test dissolution results. The default value is "test.txt" corresponding to the test.txt file provided as tutorial data

input_file_reference_sample
This variable provides name of the input file for reference dissolution results. The default value is "ref.txt" corresponding to the ref.txt file provided as tutorial data

output_file_report
This is the report file name to be generated for logging all results. The default value is "report.txt".

my_85_percent_auto_rule
This variable controls automatic procedure for cutting of the profiles when crossing the threshold of 85% dissolution. Available options are: 0 - never use it (never adjust the profiles); 1 - whenever one of the profiles exceeds 85% of dissolution then cut both the profiles, regardless of which one is the first one; 2 - only when both profiles exceed 85% then cut their terminal parts
The default value is 2

bootstrap_number
Number of bootstrap runs. The default value is 1000.

CI_probability_range
Confidence interval probability in percentages. The default value is 90

sampling_mode
Two sampling modes are introduced for bootstrapping: 1 - individual values drawn from the pool of each time-point, meaning each time point is treated separately and the profiles are generated "de novo"; 2- whole profiles as blocks for bootstrapping menaning that bootstrap samples are created from the original profiles only - no "de novo" generated profiles are introduced.
The default value is 2

boot_package_simulation_type
Options of boot package are available for two bootstrap scenarios: "ordinary"; "balanced". For more detailed understanding please refer to the boot package manual (https://cran.r-project.org/web/packages/boot/boot.pdf)
The default value is "ordinary"

calculate_exp_value_f2
Selection of statistic to be bootstrapped. If TRUE then expected value of f2, E(f2), is calculted, if FALSE then classical f2 is used. The default value is FALSE 

4. Output
Ouptut is provided both on standard output (Rout file) and report file (output_file_report). The latter introduces formatting of bootstrap samples with clearly marked reference and test dissolution data


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    This program comes with ABSOLUTELY NO WARRANTY
    This is free software, and you are welcome to redistribute it
    under certain conditions. Please find a LICENSE file to look 
    for a more detailed description of terms and conditions based on the 
    GNU GPLv3 license in the LICENSE.txt file
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