IDEAS home Printed from https://ideas.repec.org/a/gam/jmathe/v13y2025i8p1273-d1633408.html
   My bibliography  Save this article

Advances in Clinical Trial Design: Employing Adaptive Multiple Testing and Neyman Allocation for Unequal Samples

Author

Listed:
  • Hanan Hammouri

    (Department of Mathematics and Statistics, Jordan University of Science and Technology, Irbid 22110, Jordan)

  • Muna Salman

    (Department of Mathematics and Statistics, Jordan University of Science and Technology, Irbid 22110, Jordan)

  • Mohammed Ali

    (Department of Mathematics and Statistics, Jordan University of Science and Technology, Irbid 22110, Jordan)

  • Ruwa Abdel Muhsen

    (Department of Mathematical Sciences, New Mexico State University, Las Cruces, NM 88001, USA)

Abstract

This study introduces a new method that combines three distinct approaches for comparing two treatments: Neyman allocation, the O’Brien and Fleming multiple testing procedure, and a system of different sample weights at different stages. This new approach is called the Neyman Weighted Multiple Testing Procedure (NWMP). Each of these adaptive designs “individually” has proven beneficial for clinical research by removing constraints that can limit clinical trials. The advantages of these three methods are merged into a single, innovative approach that demonstrates increased efficiency in this work. The multiple testing procedure allows for trials to be stopped before their chosen time frame if one treatment is more effective. Neyman allocation is a statistically sound method designed to enhance the efficiency and precision of estimates. It strategically allocates resources or sample sizes to maximize the quality of statistical inference, considering practical constraints. Additionally, using different weights in this method provides greater flexibility, allowing for the effective distribution of sample sizes across various stages of the research. This study demonstrates that the new method maintains similar efficiency in terms of the Type I error rate and statistical power compared to the O’Brien and Fleming test while offering additional flexibility. Furthermore, the research includes examples of both real and hypothetical cases to illustrate the developed procedure.

Suggested Citation

  • Hanan Hammouri & Muna Salman & Mohammed Ali & Ruwa Abdel Muhsen, 2025. "Advances in Clinical Trial Design: Employing Adaptive Multiple Testing and Neyman Allocation for Unequal Samples," Mathematics, MDPI, vol. 13(8), pages 1-23, April.
  • Handle: RePEc:gam:jmathe:v:13:y:2025:i:8:p:1273-:d:1633408
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/2227-7390/13/8/1273/pdf
    Download Restriction: no

    File URL: https://www.mdpi.com/2227-7390/13/8/1273/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Hanan Hammouri & Mohammed Ali & Marwan Alquran & Areen Alquran & Ruwa Abdel Muhsen & Belal Alomari, 2023. "Adaptive Multiple Testing Procedure for Clinical Trials with Urn Allocation," Mathematics, MDPI, vol. 11(18), pages 1-20, September.
    2. William F. Rosenberger & Nigel Stallard & Anastasia Ivanova & Cherice N. Harper & Michelle L. Ricks, 2001. "Optimal Adaptive Designs for Binary Response Trials," Biometrics, The International Biometric Society, vol. 57(3), pages 909-913, September.
    3. Alessandro Baldi Antognini & Alessandra Giovagnoli, 2010. "Compound optimal allocation for individual and collective ethics in binary clinical trials," Biometrika, Biometrika Trust, vol. 97(4), pages 935-946.
    4. Belmiro P. M. Duarte & Anthony C. Atkinson & David Pedrosa & Marlena van Munster, 2024. "Compound Optimum Designs for Clinical Trials in Personalized Medicine," Mathematics, MDPI, vol. 12(19), pages 1-20, September.
    5. Hanan Hammouri & Marwan Alquran & Ruwa Abdel Muhsen & Jaser Altahat, 2022. "Optimal Weighted Multiple-Testing Procedure for Clinical Trials," Mathematics, MDPI, vol. 10(12), pages 1-19, June.
    6. A. C. Atkinson, 2015. "Optimum designs for two treatments with unequal variances in the presence of covariates," Biometrika, Biometrika Trust, vol. 102(2), pages 494-499.
    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. Alessandro Baldi Antognini & Marco Novelli & Maroussa Zagoraiou, 2022. "A simple solution to the inadequacy of asymptotic likelihood-based inference for response-adaptive clinical trials," Statistical Papers, Springer, vol. 63(1), pages 157-180, February.
    2. Yanqing Yi & Yuan Yuan, 2013. "An optimal allocation for response-adaptive designs," Journal of Applied Statistics, Taylor & Francis Journals, vol. 40(9), pages 1996-2008, September.
    3. Atkinson, Anthony C. & Biswas, Atanu, 2017. "Optimal response and covariate-adaptive biased-coin designs for clinical trials with continuous multivariate or longitudinal responses," LSE Research Online Documents on Economics 66761, London School of Economics and Political Science, LSE Library.
    4. Jianhua Hu & Hongjian Zhu & Feifang Hu, 2015. "A Unified Family of Covariate-Adjusted Response-Adaptive Designs Based on Efficiency and Ethics," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 110(509), pages 357-367, March.
    5. Atkinson, Anthony C. & Biswas, Atanu, 2017. "Optimal response and covariate-adaptive biased-coin designs for clinical trials with continuous multivariate or longitudinal responses," Computational Statistics & Data Analysis, Elsevier, vol. 113(C), pages 297-310.
    6. Belmiro P. M. Duarte & Anthony C. Atkinson & David Pedrosa & Marlena van Munster, 2024. "Compound Optimum Designs for Clinical Trials in Personalized Medicine," Mathematics, MDPI, vol. 12(19), pages 1-20, September.
    7. Yi, Yanqing & Wang, Xikui, 2023. "A Markov decision process for response adaptive designs," Econometrics and Statistics, Elsevier, vol. 25(C), pages 125-133.
    8. Alessandro Baldi Antognini & Marco Novelli & Maroussa Zagoraiou, 2022. "A new inferential approach for response-adaptive clinical trials: the variance-stabilized bootstrap," TEST: An Official Journal of the Spanish Society of Statistics and Operations Research, Springer;Sociedad de Estadística e Investigación Operativa, vol. 31(1), pages 235-254, March.
    9. Uttam Bandyopadhyay & Atanu Biswas & Shirsendu Mukherjee, 2009. "Adaptive two-treatment two-period crossover design for binary treatment responses incorporating carry-over effects," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 18(1), pages 13-33, March.
    10. Hengtao Zhang & Guosheng Yin, 2021. "Response‐adaptive rerandomization," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 70(5), pages 1281-1298, November.
    11. Yu, Jun & Meng, Xiran & Wang, Yaping, 2023. "Optimal designs for semi-parametric dose-response models under random contamination," Computational Statistics & Data Analysis, Elsevier, vol. 178(C).
    12. Hassan Farooq & Sajid Ali & Ismail Shah & Ibrahim A. Nafisah & Mohammed M. A. Almazah, 2025. "Adaptive Clinical Trials and Sample Size Determination in the Presence of Measurement Error and Heterogeneity," Stats, MDPI, vol. 8(2), pages 1-34, April.
    13. Hanan Hammouri & Marwan Alquran & Ruwa Abdel Muhsen & Jaser Altahat, 2022. "Optimal Weighted Multiple-Testing Procedure for Clinical Trials," Mathematics, MDPI, vol. 10(12), pages 1-19, June.
    14. Ruicheng Ao & Hongyu Chen & David Simchi-Levi, 2024. "Prediction-Guided Active Experiments," Papers 2411.12036, arXiv.org, revised Nov 2024.
    15. Biswas, Atanu & Bhattacharya, Rahul, 2010. "An optimal response-adaptive design with dual constraints," Statistics & Probability Letters, Elsevier, vol. 80(3-4), pages 177-185, February.
    16. Jennifer Proper & Thomas A. Murray, 2023. "An alternative metric for evaluating the potential patient benefit of response‐adaptive randomization procedures," Biometrics, The International Biometric Society, vol. 79(2), pages 1433-1445, June.
    17. Li-Xin, Zhang, 2006. "Asymptotic results on a class of adaptive multi-treatment designs," Journal of Multivariate Analysis, Elsevier, vol. 97(3), pages 586-605, March.
    18. Mandal, Saumen & Biswas, Atanu & Trandafir, Paula Camelia & Islam Chowdhury, Mohammad Ziaul, 2013. "Optimal target allocation proportion for correlated binary responses in a 2×2 setup," Statistics & Probability Letters, Elsevier, vol. 83(9), pages 1991-1997.
    19. Chambaz Antoine & van der Laan Mark J., 2011. "Targeting the Optimal Design in Randomized Clinical Trials with Binary Outcomes and No Covariate: Theoretical Study," The International Journal of Biostatistics, De Gruyter, vol. 7(1), pages 1-32, January.
    20. Alessandra Giovagnoli, 2021. "The Bayesian Design of Adaptive Clinical Trials," IJERPH, MDPI, vol. 18(2), pages 1-15, January.

    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:gam:jmathe:v:13:y:2025:i:8:p:1273-:d:1633408. 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: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    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.