2026-04-04T22:38:12Zhttps://openaccess.uoc.edu/server/oai/requestoai:openaccess.uoc.edu:10609/1371512025-07-04T12:44:01Zcom_10609_4421com_10609_67col_10609_39862col_10609_92386
Repositori Institucional (O2)
author
Berger, Vance W.
author
Bour, Louis Joseph
author
Carter, Kerstine
author
Chipman, Jonathan J.
author
Everett, Colin C.
author
Heussen, Nicole
author
Hewitt, Catherine
author
Hilgers, Ralf-Dieter
author
Luo, Yuqun Abigail
author
Renteria Aguirregabiria, Jone
author
Ryeznik, Yevgen
author
Sverdlov, Oleksandr
author
Uschner, Diane
other
Universitat Oberta de Catalunya (UOC)
2022-01-07T17:51:17Z
2022-01-07T17:51:17Z
2021-08-16
Berger, V., Bour, L., Carter, K. et al. A roadmap to using randomization in clinical trials. BMC Med Res Methodol 21, 168 (2021). https://doi.org/10.1186/s12874-021-01303-z
1471-2288
https://hdl.handle.net/10609/137151
https://doi.org/10.1186/s12874-021-01303-z
Background: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available. The goal of this paper is to present a systematic roadmap for the choice and application of a restricted randomization procedure in a clinical trial. Methods: We survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice. Results: Restricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size. Conclusions: The choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.
eng
balance
randomization-based test
restricted randomization design
validity
A roadmap to using randomization in clinical trials
info:eu-repo/semantics/article
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
URL
https://openaccess.uoc.edu/bitstreams/e3f290d1-ce06-4904-b579-001611297ac9/download
File
MD5
780a8588656a21f14dd4c86de802147e
3310140
application/pdf
A roadmap to using randomization.pdf