IDEAS home Printed from https://ideas.repec.org/a/oup/biomet/v98y2011i4p845-860.html
   My bibliography  Save this article

Optimizing randomized trial designs to distinguish which subpopulations benefit from treatment

Author

Listed:
  • M. Rosenblum
  • M. J. van der Laan

Abstract

It is a challenge to evaluate experimental treatments where it is suspected that the treatment effect may only be strong for certain subpopulations, such as those having a high initial severity of disease, or those having a particular gene variant. Standard randomized controlled trials can have low power in such situations. They also are not optimized to distinguish which subpopulations benefit from a treatment. With the goal of overcoming these limitations, we consider randomized trial designs in which the criteria for patient enrollment may be changed, in a preplanned manner, based on interim analyses. Since such designs allow data-dependent changes to the population enrolled, care must be taken to ensure strong control of the familywise Type I error rate. Our main contribution is a general method for constructing randomized trial designs that allow changes to the population enrolled based on interim data using a prespecified decision rule, for which the asymptotic, familywise Type I error rate is strongly controlled at a specified level α. As a demonstration of our method, we prove new, sharp results for a simple, two-stage enrichment design. We then compare this design to fixed designs, focusing on each design's ability to determine the overall and subpopulation-specific treatment effects. Copyright 2011, Oxford University Press.

Suggested Citation

  • M. Rosenblum & M. J. van der Laan, 2011. "Optimizing randomized trial designs to distinguish which subpopulations benefit from treatment," Biometrika, Biometrika Trust, vol. 98(4), pages 845-860.
    • Handle: RePEc:oup:biomet:v:98:y:2011:i:4:p:845-860
    as

    Download full text from publisher

    File URL: http://hdl.handle.net/10.1093/biomet/asr055
    Download Restriction: Access to full text is restricted to subscribers.
    ---><---

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

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Alessandro Baldi Antognini & Rosamarie Frieri & Maroussa Zagoraiou, 2023. "New insights into adaptive enrichment designs," Statistical Papers, Springer, vol. 64(4), pages 1305-1328, August.
    2. Zhiwei Zhang & Meijuan Li & Min Lin & Guoxing Soon & Tom Greene & Changyu Shen, 2017. "Subgroup selection in adaptive signature designs of confirmatory clinical trials," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 66(2), pages 345-361, February.
    3. Rui Tang & Xiaoye Ma & Hui Yang & Michael Wolf, 2018. "Biomarker-Defined Subgroup Selection Adaptive Design for Phase III Confirmatory Trial with Time-to-Event Data: Comparing Group Sequential and Various Adaptive Enrichment Designs," Statistics in Biosciences, Springer;International Chinese Statistical Association, vol. 10(2), pages 371-404, August.
    4. Michael Rosenblum & Ethan X. Fang & Han Liu, 2020. "Optimal, two‐stage, adaptive enrichment designs for randomized trials, using sparse linear programming," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(3), pages 749-772, July.
    5. Susan Athey & Guido Imbens, 2015. "Recursive Partitioning for Heterogeneous Causal Effects," Papers 1504.01132, arXiv.org, revised Dec 2015.

    More about this item

    Statistics

    Access and download statistics

    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:oup:biomet:v:98:y:2011:i:4:p:845-860. 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: Oxford University Press (email available below). General contact details of provider: https://academic.oup.com/biomet .

    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.