IDEAS home Printed from https://ideas.repec.org/a/bla/biomet/v79y2023i4p2815-2829.html
   My bibliography  Save this article

Optimizing treatment allocation in randomized clinical trials by leveraging baseline covariates

Author

Listed:
  • Wei Zhang
  • Zhiwei Zhang
  • Aiyi Liu

Abstract

We consider the problem of optimizing treatment allocation for statistical efficiency in randomized clinical trials. Optimal allocation has been studied previously for simple treatment effect estimators such as the sample mean difference, which are not fully efficient in the presence of baseline covariates. More efficient estimators can be obtained by incorporating covariate information, and modern machine learning methods make it increasingly feasible to approach full efficiency. Accordingly, we derive the optimal allocation ratio by maximizing the design efficiency of a randomized trial, assuming that an efficient estimator will be used for analysis. We then expand the scope of optimization by considering covariate‐dependent randomization (CDR), which has some flavor of an observational study but provides the same level of scientific rigor as a standard randomized trial. We describe treatment effect estimators that are consistent, asymptotically normal, and (nearly) efficient under CDR, and derive the optimal propensity score by maximizing the design efficiency of a CDR trial (under the assumption that an efficient estimator will be used for analysis). Our optimality results translate into optimal designs that improve upon standard practice. Real‐world examples and simulation results demonstrate that the proposed designs can produce substantial efficiency improvements in realistic settings.

Suggested Citation

  • Wei Zhang & Zhiwei Zhang & Aiyi Liu, 2023. "Optimizing treatment allocation in randomized clinical trials by leveraging baseline covariates," Biometrics, The International Biometric Society, vol. 79(4), pages 2815-2829, December.
  • Handle: RePEc:bla:biomet:v:79:y:2023:i:4:p:2815-2829
    DOI: 10.1111/biom.13914
    as

    Download full text from publisher

    File URL: https://doi.org/10.1111/biom.13914
    Download Restriction: no

    File URL: https://libkey.io/10.1111/biom.13914?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. Victor Chernozhukov & Denis Chetverikov & Mert Demirer & Esther Duflo & Christian Hansen & Whitney Newey & James Robins, 2018. "Double/debiased machine learning for treatment and structural parameters," Econometrics Journal, Royal Economic Society, vol. 21(1), pages 1-68, February.
    2. Min Zhang & Anastasios A. Tsiatis & Marie Davidian, 2008. "Improving Efficiency of Inferences in Randomized Clinical Trials Using Auxiliary Covariates," Biometrics, The International Biometric Society, vol. 64(3), pages 707-715, September.
    3. Rosenblum Michael & van der Laan Mark J., 2010. "Simple, Efficient Estimators of Treatment Effects in Randomized Trials Using Generalized Linear Models to Leverage Baseline Variables," The International Journal of Biostatistics, De Gruyter, vol. 6(1), pages 1-44, April.
    4. Rubin Daniel B & van der Laan Mark J., 2008. "Empirical Efficiency Maximization: Improved Locally Efficient Covariate Adjustment in Randomized Experiments and Survival Analysis," The International Journal of Biostatistics, De Gruyter, vol. 4(1), pages 1-42, May.
    5. Anthony C. Atkinson, 2002. "The comparison of designs for sequential clinical trials with covariate information," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 165(2), pages 349-373, June.
    6. Zhiwei Zhang & Wei Li & Hui Zhang, 2020. "Efficient Estimation of Mann–Whitney-Type Effect Measures for Right-Censored Survival Outcomes in Randomized Clinical Trials," Statistics in Biosciences, Springer;International Chinese Statistical Association, vol. 12(2), pages 246-262, July.
    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. Nicholas Williams & Michael Rosenblum & Iván Díaz, 2022. "Optimising precision and power by machine learning in randomised trials with ordinal and time‐to‐event outcomes with an application to COVID‐19," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 185(4), pages 2156-2178, October.
    2. Wang, Qihua & Su, Miaomiao & Wang, Ruoyu, 2021. "A beyond multiple robust approach for missing response problem," Computational Statistics & Data Analysis, Elsevier, vol. 155(C).
    3. David Benkeser & Iván Díaz & Alex Luedtke & Jodi Segal & Daniel Scharfstein & Michael Rosenblum, 2021. "Improving precision and power in randomized trials for COVID‐19 treatments using covariate adjustment, for binary, ordinal, and time‐to‐event outcomes," Biometrics, The International Biometric Society, vol. 77(4), pages 1467-1481, December.
    4. Rosenblum Michael & van der Laan Mark J., 2010. "Simple, Efficient Estimators of Treatment Effects in Randomized Trials Using Generalized Linear Models to Leverage Baseline Variables," The International Journal of Biostatistics, De Gruyter, vol. 6(1), pages 1-44, April.
    5. Yuehao Bai & Jizhou Liu & Azeem M. Shaikh & Max Tabord-Meehan, 2023. "On the Efficiency of Finely Stratified Experiments," Papers 2307.15181, arXiv.org, revised Aug 2024.
    6. Ruoyao Shi, 2021. "An Averaging Estimator for Two Step M Estimation in Semiparametric Models," Working Papers 202105, University of California at Riverside, Department of Economics.
    7. Alexandre Belloni & Victor Chernozhukov & Denis Chetverikov & Christian Hansen & Kengo Kato, 2018. "High-dimensional econometrics and regularized GMM," CeMMAP working papers CWP35/18, Centre for Microdata Methods and Practice, Institute for Fiscal Studies.
    8. Nicolaj N. Mühlbach, 2020. "Tree-based Synthetic Control Methods: Consequences of moving the US Embassy," CREATES Research Papers 2020-04, Department of Economics and Business Economics, Aarhus University.
    9. Kyle Colangelo & Ying-Ying Lee, 2019. "Double debiased machine learning nonparametric inference with continuous treatments," CeMMAP working papers CWP72/19, Centre for Microdata Methods and Practice, Institute for Fiscal Studies.
    10. Sant’Anna, Pedro H.C. & Zhao, Jun, 2020. "Doubly robust difference-in-differences estimators," Journal of Econometrics, Elsevier, vol. 219(1), pages 101-122.
    11. Ruoxuan Xiong & Allison Koenecke & Michael Powell & Zhu Shen & Joshua T. Vogelstein & Susan Athey, 2021. "Federated Causal Inference in Heterogeneous Observational Data," Papers 2107.11732, arXiv.org, revised Apr 2023.
    12. Susan Athey & Guido W. Imbens & Stefan Wager, 2018. "Approximate residual balancing: debiased inference of average treatment effects in high dimensions," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 80(4), pages 597-623, September.
    13. Jelena Bradic & Weijie Ji & Yuqian Zhang, 2021. "High-dimensional Inference for Dynamic Treatment Effects," Papers 2110.04924, arXiv.org, revised May 2023.
    14. Davide Viviano & Jelena Bradic, 2019. "Synthetic learner: model-free inference on treatments over time," Papers 1904.01490, arXiv.org, revised Aug 2022.
    15. Kirill Borusyak & Peter Hull & Xavier Jaravel, 2023. "Design-Based Identification with Formula Instruments: A Review," NBER Working Papers 31393, National Bureau of Economic Research, Inc.
    16. Yoganathan, Vignesh & Osburg, Victoria-Sophie, 2024. "The mind in the machine: Estimating mind perception's effect on user satisfaction with voice-based conversational agents," Journal of Business Research, Elsevier, vol. 175(C).
    17. Sallin, Aurelién, 2021. "Estimating returns to special education: combining machine learning and text analysis to address confounding," Economics Working Paper Series 2109, University of St. Gallen, School of Economics and Political Science.
    18. Pedro Carneiro & Sokbae Lee & Daniel Wilhelm, 2020. "Optimal data collection for randomized control trials," The Econometrics Journal, Royal Economic Society, vol. 23(1), pages 1-31.
    19. Sung Jae Jun & Sokbae Lee, 2024. "Causal Inference Under Outcome-Based Sampling with Monotonicity Assumptions," Journal of Business & Economic Statistics, Taylor & Francis Journals, vol. 42(3), pages 998-1009, July.
    20. Soren Blomquist & Anil Kumar & Che-Yuan Liang & Whitney K. Newey, 2022. "Nonlinear Budget Set Regressions for the Random Utility Model," Working Papers 2219, Federal Reserve Bank of Dallas.

    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:4:p:2815-2829. 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.