IDEAS home Printed from https://ideas.repec.org/a/gam/jmathe/v12y2024i19p3007-d1486729.html
   My bibliography  Save this article

Compound Optimum Designs for Clinical Trials in Personalized Medicine

Author

Listed:
  • Belmiro P. M. Duarte

    (Instituto Politécnico de Coimbra, Instituto Superior de Engenharia de Coimbra, Rua Pedro Nunes, 3030-199 Coimbra, Portugal
    INESC Coimbra—Instituto de Engenharia de Sistemas e Computadores de Coimbra, Universidade de Coimbra, Rua Sílvio Lima—Pólo II, 3030-790 Coimbra, Portugal
    Research Center for Chemical Engineering and Renewable Resources for Sustainability, Universidade de Coimbra, Rua Sílvio Lima—Pólo II, 3030-790 Coimbra, Portugal)

  • Anthony C. Atkinson

    (Department of Statistics, London School of Economics, London WC2A 2AE, UK)

  • David Pedrosa

    (Department of Neurology, University Hospital Marburg, 35043 Marburg, Germany
    Centre of Brain, Mind and Behavior, Philipps-University Marburg, 35043 Marburg, Germany)

  • Marlena van Munster

    (Department of Neurology, University Hospital Marburg, 35043 Marburg, Germany)

Abstract

We consider optimal designs for clinical trials when response variance depends on treatment and covariates are included in the response model. These designs are generalizations of Neyman allocation, and commonly employed in personalized medicine where external covariates linearly affect the response. Very often, these designs aim at maximizing the amount of information gathered but fail to assure ethical requirements. We analyze compound optimal designs that maximize a criterion weighting the amount of information and the reward of allocating the patients to the most effective/least risky treatment. We develop a general representation for static (a priori) allocation and propose a semidefinite programming (SDP) formulation to support their numerical computation. This setup is extended assuming the variance and the parameters of the response of all treatments are unknown and an adaptive sequential optimal design scheme is implemented and used for demonstration. Purely information theoretic designs for the same allocation have been addressed elsewhere, and we use them to support the techniques applied to compound designs.

Suggested Citation

  • 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.
    • Handle: RePEc:gam:jmathe:v:12:y:2024:i:19:p:3007-:d:1486729
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/2227-7390/12/19/3007/pdf
    Download Restriction: no
    File URL: https://www.mdpi.com/2227-7390/12/19/3007/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Nathan Kallus, 2021. "On the optimality of randomization in experimental design: How to randomize for minimax variance and design‐based inference," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 83(2), pages 404-409, April.
    2. 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.
    3. 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.
    4. Holger Dette, 1997. "Designing Experiments with Respect to ‘Standardized’ Optimality Criteria," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 59(1), pages 97-110.
    5. Dimitris Bertsimas & Mac Johnson & Nathan Kallus, 2015. "The Power of Optimization Over Randomization in Designing Experiments Involving Small Samples," Operations Research, INFORMS, vol. 63(4), pages 868-876, August.
    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.
    7. 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.
    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. 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.
    2. 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.
    3. Nikhil Bhat & Vivek F. Farias & Ciamac C. Moallemi & Deeksha Sinha, 2020. "Near-Optimal A-B Testing," Management Science, INFORMS, vol. 66(10), pages 4477-4495, October.
    4. 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.
    5. Qiong Zhang & Amin Khademi & Yongjia Song, 2022. "Min-Max Optimal Design of Two-Armed Trials with Side Information," INFORMS Journal on Computing, INFORMS, vol. 34(1), pages 165-182, January.
    6. Yi, Yanqing & Wang, Xikui, 2023. "A Markov decision process for response adaptive designs," Econometrics and Statistics, Elsevier, vol. 25(C), pages 125-133.
    7. 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.
    8. 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.
    9. Dennis Schmidt & Rainer Schwabe, 2015. "On optimal designs for censored data," Metrika: International Journal for Theoretical and Applied Statistics, Springer, vol. 78(3), pages 237-257, April.
    10. 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).
    11. Lenka Filová & Mária Trnovská & Radoslav Harman, 2012. "Computing maximin efficient experimental designs using the methods of semidefinite programming," Metrika: International Journal for Theoretical and Applied Statistics, Springer, vol. 75(5), pages 709-719, July.
    12. Jinglong Zhao, 2024. "Experimental Design For Causal Inference Through An Optimization Lens," Papers 2408.09607, arXiv.org, revised Aug 2024.
    13. Yuchen Hu & Henry Zhu & Emma Brunskill & Stefan Wager, 2024. "Minimax-Regret Sample Selection in Randomized Experiments," Papers 2403.01386, arXiv.org, revised Jun 2024.
    14. Pepelyshev, Andrey & Melas, Viatcheslav B. & Strigul, Nikolay & Dette, Holger, 2004. "Design of experiments for the Monod model : robust and efficient designs," Technical Reports 2004,36, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    15. Lei He & Rong-Xian Yue, 2020. "R-optimal designs for trigonometric regression models," Statistical Papers, Springer, vol. 61(5), pages 1997-2013, October.
    16. Dette, Holger & O'Brien, Timothy E., 2003. "Efficient experimental design for the Behrens-Fisher problem with application to bioassay," Technical Reports 2003,21, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    17. Eszter Czibor & David Jimenez‐Gomez & John A. List, 2019. "The Dozen Things Experimental Economists Should Do (More of)," Southern Economic Journal, John Wiley & Sons, vol. 86(2), pages 371-432, October.
    18. D. R. Cox, 2009. "Randomization in the Design of Experiments," International Statistical Review, International Statistical Institute, vol. 77(3), pages 415-429, December.
    19. Harman, Radoslav & Jurík, Tomás, 2008. "Computing c-optimal experimental designs using the simplex method of linear programming," Computational Statistics & Data Analysis, Elsevier, vol. 53(2), pages 247-254, December.
    20. Hertel, Ida & Kohler, Michael, 2013. "Estimation of the optimal design of a nonlinear parametric regression problem via Monte Carlo experiments," Computational Statistics & Data Analysis, Elsevier, vol. 59(C), pages 1-12.

    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:12:y:2024:i:19:p:3007-:d:1486729. 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.