IDEAS home Printed from https://ideas.repec.org/a/eee/csdana/v75y2014icp151-161.html
   My bibliography  Save this article

Consistency-adjusted alpha allocation methods for a time-to-event analysis of composite endpoints

Author

Listed:
  • Rauch, G.
  • Wirths, M.
  • Kieser, M.

Abstract

Composite endpoints are often used as primary efficacy endpoints, particularly in the field of oncology and cardiology. These endpoints combine several time-to-event variables of interest within a single time-to-first-event variable. Thereby, it is intended to enlarge the expected effect size and thus to increase the power of the clinical trial. However, the interpretation of composite endpoints can be difficult, as the observed effect for the composite does not necessarily reflect the effects of the single components. Therefore, it might not be adequate to judge the efficacy of the new intervention exclusively on the composite effect. Including the most relevant components in an efficacy claim assessed by a confirmatory test strategy could overcome this problem but imposes the problem of multiplicity. Moreover, to show non-inferiority or even superiority of the new intervention with respect to single components is usually not realistic in these settings as the expected individual effects are small. Recently, consistency-adjusted alpha allocation methods were proposed in the literature which can be used and extended to establish a new efficacy claim for a composite endpoint and one main component. The power properties of the new approach are compared to the alternative efficacy claim of proving superiority for the composite and non-inferiority for the main component. Moreover, the methods are illustrated with a clinical trial example. Thereby, the general problem of correlation-adjusted multiple testing procedures is addressed by applying a bootstrapping algorithm to estimate the special correlation structure between a composite endpoint and an individual component in the time-to-event setting.11The R code is available online as supplementary material (see Appendix C).

Suggested Citation

  • Rauch, G. & Wirths, M. & Kieser, M., 2014. "Consistency-adjusted alpha allocation methods for a time-to-event analysis of composite endpoints," Computational Statistics & Data Analysis, Elsevier, vol. 75(C), pages 151-161.
  • Handle: RePEc:eee:csdana:v:75:y:2014:i:c:p:151-161
    DOI: 10.1016/j.csda.2014.01.017
    as

    Download full text from publisher

    File URL: http://www.sciencedirect.com/science/article/pii/S0167947314000280
    Download Restriction: Full text for ScienceDirect subscribers only.

    File URL: https://libkey.io/10.1016/j.csda.2014.01.017?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:eee:csdana:v:75:y:2014:i:c:p:151-161. See general information about how to correct material in RePEc.

    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.

    We have no bibliographic references for this item. You can help adding them by using 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 RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Catherine Liu (email available below). General contact details of provider: http://www.elsevier.com/locate/csda .

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

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.