Advanced Search
MyIDEAS: Login to save this article or follow this journal

Parametric non-mixture cure models for schedule finding of therapeutic agents

Contents:

Author Info

  • Changying A. Liu
  • Thomas M. Braun
Registered author(s):

    Abstract

    We propose a phase I clinical trial design that seeks to determine the cumulative safety of a series of administrations of a fixed dose of an investigational agent. In contrast with traditional phase I trials that are designed solely to find the maximum tolerated dose of the agent, our design instead identifies a maximum tolerated schedule that includes a maximum tolerated dose as well as a vector of recommended administration times. Our model is based on a non-mixture cure model that constrains the probability of dose limiting toxicity for all patients to increase monotonically with both dose and the number of administrations received. We assume a specific parametric hazard function for each administration and compute the total hazard of dose limiting toxicity for a schedule as a sum of individual administration hazards. Throughout a variety of settings motivated by an actual study in allogeneic bone marrow transplant recipients, we demonstrate that our approach has excellent operating characteristics and performs as well as the only other currently published design for schedule finding studies. We also present arguments for the preference of our non-mixture cure model over the existing model. Copyright (c) 2009 Royal Statistical Society.

    Download Info

    If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
    File URL: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1467-9876.2008.00660.x
    File Function: link to full text
    Download Restriction: Access to full text is restricted to subscribers.

    As the access to this document is restricted, you may want to look for a different version under "Related research" (further below) or search for a different version of it.

    Bibliographic Info

    Article provided by Royal Statistical Society in its journal Journal of the Royal Statistical Society: Series C (Applied Statistics).

    Volume (Year): 58 (2009)
    Issue (Month): 2 ()
    Pages: 225-236

    as in new window
    Handle: RePEc:bla:jorssc:v:58:y:2009:i:2:p:225-236

    Contact details of provider:
    Postal: 12 Errol Street, London EC1Y 8LX, United Kingdom
    Phone: -44-171-638-8998
    Fax: -44-171-256-7598
    Email:
    Web page: http://wileyonlinelibrary.com/journal/rssc
    More information through EDIRC

    Order Information:
    Web: http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1467-9876&doi=10.1111/(ISSN)1467-9876

    Related research

    Keywords:

    References

    No references listed on IDEAS
    You can help add them by filling out this form.

    Citations

    Lists

    This item is not listed on Wikipedia, on a reading list or among the top items on IDEAS.

    Statistics

    Access and download statistics

    Corrections

    When requesting a correction, please mention this item's handle: RePEc:bla:jorssc:v:58:y:2009:i:2:p:225-236. See general information about how to correct material in RePEc.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: (Wiley-Blackwell Digital Licensing) or (Christopher F. Baum).

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If references are entirely missing, you can add them using this form.

    If the full references list an item that is present in RePEc, but the system did not link to it, you can help with this form.

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your profile, as there may be some citations waiting for confirmation.

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.