IDEAS home Printed from https://ideas.repec.org/a/bla/biomet/v79y2023i1p381-393.html
   My bibliography  Save this article

Inference in response‐adaptive clinical trials when the enrolled population varies over time

Author

Listed:
  • Massimiliano Russo
  • Steffen Ventz
  • Victoria Wang
  • Lorenzo Trippa

Abstract

A common assumption of data analysis in clinical trials is that the patient population, as well as treatment effects, do not vary during the course of the study. However, when trials enroll patients over several years, this hypothesis may be violated. Ignoring variations of the outcome distributions over time, under the control and experimental treatments, can lead to biased treatment effect estimates and poor control of false positive results. We propose and compare two procedures that account for possible variations of the outcome distributions over time, to correct treatment effect estimates, and to control type‐I error rates. The first procedure models trends of patient outcomes with splines. The second leverages conditional inference principles, which have been introduced to analyze randomized trials when patient prognostic profiles are unbalanced across arms. These two procedures are applicable in response‐adaptive clinical trials. We illustrate the consequences of trends in the outcome distributions in response‐adaptive designs and in platform trials, and investigate the proposed methods in the analysis of a glioblastoma study.

Suggested Citation

  • Massimiliano Russo & Steffen Ventz & Victoria Wang & Lorenzo Trippa, 2023. "Inference in response‐adaptive clinical trials when the enrolled population varies over time," Biometrics, The International Biometric Society, vol. 79(1), pages 381-393, March.
    • Handle: RePEc:bla:biomet:v:79:y:2023:i:1:p:381-393
    DOI: 10.1111/biom.13582
    as

    Download full text from publisher

    File URL: https://doi.org/10.1111/biom.13582
    Download Restriction: no
    File URL: https://libkey.io/10.1111/biom.13582?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
    ---><---

    References listed on IDEAS

    as
    1. Fei Jiang & Lu Tian & Haoda Fu & Takahiro Hasegawa & L. J. Wei, 2019. "Robust Alternatives to ANCOVA for Estimating the Treatment Effect via a Randomized Comparative Study," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 114(528), pages 1854-1864, October.
    2. Guiteras, Raymond P. & Levine, David I. & Polley, Thomas H., 2016. "The pursuit of balance in sequential randomized trials," Development Engineering, Elsevier, vol. 1(C), pages 12-25.
    3. Simon N. Wood, 2003. "Thin plate regression splines," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 65(1), pages 95-114, February.
    4. Steffen Ventz & William T. Barry & Giovanni Parmigiani & Lorenzo Trippa, 2017. "Bayesian response-adaptive designs for basket trials," Biometrics, The International Biometric Society, vol. 73(3), pages 905-915, September.
    5. Vaart,A. W. van der, 2000. "Asymptotic Statistics," Cambridge Books, Cambridge University Press, number 9780521784504.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dominic Edelmann & Thomas Welchowski & Axel Benner, 2022. "A consistent version of distance covariance for right‐censored survival data and its application in hypothesis testing," Biometrics, The International Biometric Society, vol. 78(3), pages 867-879, September.
    2. M.L. Nores & M.P. Díaz, 2016. "Bootstrap hypothesis testing in generalized additive models for comparing curves of treatments in longitudinal studies," Journal of Applied Statistics, Taylor & Francis Journals, vol. 43(5), pages 810-826, April.
    3. Georgios Gioldasis & Antonio Musolesi & Michel Simioni, 2020. "Model uncertainty, nonlinearities and out-of-sample comparison: evidence from international technology diffusion," Working Papers hal-02790523, HAL.
    4. Laurent Davezies & Xavier D'Haultfoeuille & Yannick Guyonvarch, 2019. "Empirical Process Results for Exchangeable Arrays," Papers 1906.11293, arXiv.org, revised May 2020.
    5. Alexander Frankel & Maximilian Kasy, 2022. "Which Findings Should Be Published?," American Economic Journal: Microeconomics, American Economic Association, vol. 14(1), pages 1-38, February.
    6. Kasy, Maximilian, 2011. "A nonparametric test for path dependence in discrete panel data," Economics Letters, Elsevier, vol. 113(2), pages 172-175.
    7. Atı̇la Abdulkadı̇roğlu & Joshua D. Angrist & Yusuke Narita & Parag Pathak, 2022. "Breaking Ties: Regression Discontinuity Design Meets Market Design," Econometrica, Econometric Society, vol. 90(1), pages 117-151, January.
    8. Waverly Wei & Maya Petersen & Mark J van der Laan & Zeyu Zheng & Chong Wu & Jingshen Wang, 2023. "Efficient targeted learning of heterogeneous treatment effects for multiple subgroups," Biometrics, The International Biometric Society, vol. 79(3), pages 1934-1946, September.
    9. Iñaki Galán & Lorena Simón & Elena Boldo & Cristina Ortiz & Rafael Fernández-Cuenca & Cristina Linares & María José Medrano & Roberto Pastor-Barriuso, 2017. "Changes in hospitalizations for chronic respiratory diseases after two successive smoking bans in Spain," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-14, May.
    10. Yao, Haixiang & Huang, Jinbo & Li, Yong & Humphrey, Jacquelyn E., 2021. "A general approach to smooth and convex portfolio optimization using lower partial moments," Journal of Banking & Finance, Elsevier, vol. 129(C).
    11. Luo, Yu & Graham, Daniel J. & McCoy, Emma J., 2023. "Semiparametric Bayesian doubly robust causal estimation," LSE Research Online Documents on Economics 117944, London School of Economics and Political Science, LSE Library.
    12. Longhi, Christian & Musolesi, Antonio & Baumont, Catherine, 2014. "Modeling structural change in the European metropolitan areas during the process of economic integration," Economic Modelling, Elsevier, vol. 37(C), pages 395-407.
    13. Ashesh Rambachan & Jonathan Roth, 2020. "Design-Based Uncertainty for Quasi-Experiments," Papers 2008.00602, arXiv.org, revised Feb 2024.
    14. Strasak, Alexander M. & Umlauf, Nikolaus & Pfeiffer, Ruth M. & Lang, Stefan, 2011. "Comparing penalized splines and fractional polynomials for flexible modelling of the effects of continuous predictor variables," Computational Statistics & Data Analysis, Elsevier, vol. 55(4), pages 1540-1551, April.
    15. Li, J. & Nott, D.J. & Fan, Y. & Sisson, S.A., 2017. "Extending approximate Bayesian computation methods to high dimensions via a Gaussian copula model," Computational Statistics & Data Analysis, Elsevier, vol. 106(C), pages 77-89.
    16. Roberto Basile & Luigi Benfratello & Davide Castellani, 2012. "Geoadditive models for regional count data: an application to industrial location," ERSA conference papers ersa12p83, European Regional Science Association.
    17. Denis Koshelev & Alexey Ponomarenko & Sergei Seleznev, 2023. "Amortized neural networks for agent-based model forecasting," Papers 2308.05753, arXiv.org.
    18. Paolo Veneri, 2018. "Urban spatial structure in OECD cities: Is urban population decentralising or clustering?," Papers in Regional Science, Wiley Blackwell, vol. 97(4), pages 1355-1374, November.
    19. Debashis Ghosh, 2004. "Semiparametric methods for the binormal model with multiple biomarkers," The University of Michigan Department of Biostatistics Working Paper Series 1046, Berkeley Electronic Press.
    20. Schwemmer, Philipp & Güpner, Franziska & Adler, Sven & Klingbeil, Knut & Garthe, Stefan, 2016. "Modelling small-scale foraging habitat use in breeding Eurasian oystercatchers (Haematopus ostralegus) in relation to prey distribution and environmental predictors," Ecological Modelling, Elsevier, vol. 320(C), pages 322-333.

    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:bla:biomet:v:79:y:2023:i:1:p:381-393. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc 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 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: Wiley Content Delivery (email available below). General contact details of provider: http://www.blackwellpublishing.com/journal.asp?ref=0006-341X .

    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.