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Review
. 2023 Jul;54(7):1909-1919.
doi: 10.1161/STROKEAHA.122.040743. Epub 2023 Apr 20.

Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience

Wenle Zhao  1 , Sharon D Yeatts  1 , Joseph P Broderick  2 , Magdy H Selim  3 , Opeolu M Adeoye  4 , Valerie L Durkalski-Mauldin  1 , Caitlyn N Meinzer  1 , Reneé H Martin  1 , Catherine R Dillon  1 , Christy N Cassarly  1 , Keith H Pauls  1 , Jordan J Elm  1
Affiliations
Review

Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience

Wenle Zhao et al. Stroke. 2023 Jul.

Abstract

From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation. This article reviews the randomization designs for 3 trials currently enrolling in Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the SATURN (Statins in Intracerebral Hemorrhage Trial), the MOST (Multiarm Optimization of Stroke Thrombolysis Trial), and the FASTEST (Recombinant Factor VIIa for Hemorrhagic Stroke Trial). Randomization methods utilized in these trials include minimal sufficient balance, block urn design, big stick design, and step-forward randomization. Their advantages and limitations are reviewed and compared with traditional stratified permuted block design and minimization.

Keywords: allocation randomness; covariate balance; emergency treatment; multicenter clinical trial; randomization; response adaptive randomization.

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Conflict of interest statement

Disclosures Dr Zhao reports grants from National Institutes of Health. Dr Yeatts reports other intellectual property licensed to American Stroke Association; compensation from C.R. Bard, Inc & Subsidiaries for data and safety monitoring services; employment by Medical University of South Carolina; grants from National Heart, Lung, and Blood Institute; grants from National Institute of Neurological Disorders and Stroke; and compensation from Emory University for data and safety monitoring services. Dr Selim reports grants from NIH/NIA; compensation from MedRhythms, Inc for consultant services; and grants from NIH/NINDS. Dr Adeoye reports service as Chief Medical Officer for sense diagnostics and compensation from NICO Corporation for data and safety monitoring services. Dr Durkalski-Mauldin reports grants from National Institutes of Health. Dr Elm reports grants from National Institutes of Health.

Figures

Figure 1.
Figure 1.
Relative Pros and Cons of Randomization Methods
Figure 2.
Figure 2.
Subject Randomization Algorithms for Two StrokeNet Trials
Figure 3.
Figure 3.
Generic subject randomization procedure with trial specific randomization algorithm
See this image and copyright information in PMC

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