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dfpk : An R-package for Bayesian dose-finding designs using Pharmacokinetics (PK) for phase I clinical trials
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Toumazi, A., Comets, E., Alberti, C., Friede, T., Lentz, F., Stallard, Nigel, Zohar, S. and Ursino, M. (2018) dfpk : An R-package for Bayesian dose-finding designs using Pharmacokinetics (PK) for phase I clinical trials. Computer Methods and Programs in Biomedicine, 157 . pp. 163-177. doi:10.1016/j.cmpb.2018.01.023 ISSN 0169-2607.
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WRAP-dfpk-R-package-Bayesian-dose-finding-designs-Pharmacokinetics-phase-I-clinical-trials-Stallard-2018.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (1407Kb) |
Official URL: https://doi.org/10.1016/j.cmpb.2018.01.023
Abstract
Background and objective
Dose-finding, aiming at finding the maximum tolerated dose, and pharmacokinetics studies are the first in human studies in the development process of a new pharmacological treatment. In the literature, to date only few attempts have been made to combine pharmacokinetics and dose-finding and to our knowledge no software implementation is generally available. In previous papers, we proposed several Bayesian adaptive pharmacokinetics-based dose-finding designs in small populations. The objective of this work is to implement these dose-finding methods in an R package, called dfpk.
Methods
All methods were developed in a sequential Bayesian setting and Bayesian parameter estimation is carried out using the rstan package. All available pharmacokinetics and toxicity data are used to suggest the dose of the next cohort with a constraint regarding the probability of toxicity. Stopping rules are also considered for each method. The ggplot2 package is used to create summary plots of toxicities or concentration curves.
Results
For all implemented methods, dfpk provides a function (nextDose) to estimate the probability of efficacy and to suggest the dose to give to the next cohort, and a function to run trial simulations to design a trial (nsim). The sim.data function generates at each dose the toxicity value related to a pharmacokinetic measure of exposure, the AUC, with an underlying pharmacokinetic one compartmental model with linear absorption. It is included as an example since similar data-frames can be generated directly by the user and passed to nsim.
Conclusion
The developed user-friendly R package dfpk, available on the CRAN repository, supports the design of innovative dose-finding studies using PK information.
Item Type: | Journal Article | ||||||||
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Subjects: | R Medicine > RS Pharmacy and materia medica | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Drugs -- Dosage -- Computer programs, Pharmacokinetics, Bayesian statistical decision theory, Clinical trials | ||||||||
Journal or Publication Title: | Computer Methods and Programs in Biomedicine | ||||||||
Publisher: | Elsevier Ireland Ltd. | ||||||||
ISSN: | 0169-2607 | ||||||||
Official Date: | April 2018 | ||||||||
Dates: |
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Volume: | 157 | ||||||||
Page Range: | pp. 163-177 | ||||||||
DOI: | 10.1016/j.cmpb.2018.01.023 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 26 January 2018 | ||||||||
Date of first compliant Open Access: | 20 March 2018 | ||||||||
RIOXX Funder/Project Grant: |
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