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Understanding an impact of patient enrollment pattern on predictability of central (unstratified) randomization in a multi-center clinical trial
Boehringer Ingelheim Pharm GmbH & Co KG, Global Biostat & Data Sci, Ingelheim, Germany..ORCID iD: 0000-0003-4092-7874
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0003-2997-8566
Boehringer Ingelheim Pharmaceut Inc, Global Biostat & Data Sci, Ridgefield, CT USA..ORCID iD: 0009-0004-6144-2344
Merck & Co Inc, Rahway, NJ USA..ORCID iD: 0000-0002-7037-3641
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2024 (English)In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 43, no 17, p. 3313-3325Article in journal (Refereed) Published
Abstract [en]

In a multi-center randomized controlled trial (RCT) with competitive recruitment, eligible patients are enrolled sequentially by different study centers and are randomized to treatment groups using the chosen randomization method. Given the stochastic nature of the recruitment process, some centers may enroll more patients than others, and in some instances, a center may enroll multiple patients in a row, for example, on a given day. If the study is open-label, the investigators might be able to make intelligent guesses on upcoming treatment assignments in the randomization sequence, even if the trial is centrally randomized and not stratified by center. In this paper, we use enrollment data inspired by a real multi-center RCT to quantify the susceptibility of two restricted randomization procedures, the permuted block design and the big stick design, to selection bias under the convergence strategy of Blackwell and Hodges (1957) applied at the center level. We provide simulation evidence that the expected proportion of correct guesses may be greater than 50% (i.e., an increased risk of selection bias) and depends on the chosen randomization method and the number of study patients recruited by a given center that takes consecutive positions on the central allocation schedule. We propose some strategies for ensuring stronger encryption of the randomization sequence to mitigate the risk of selection bias.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024. Vol. 43, no 17, p. 3313-3325
Keywords [en]
big stick design, multi-center clinical trial, permuted block randomization, selection bias
National Category
Probability Theory and Statistics
Identifiers
URN: urn:nbn:se:uu:diva-542417DOI: 10.1002/sim.10117ISI: 001237514400001PubMedID: 38831520Scopus ID: 2-s2.0-85195215982OAI: oai:DiVA.org:uu-542417DiVA, id: diva2:1912590
Available from: 2024-11-12 Created: 2024-11-12 Last updated: 2026-06-09Bibliographically approved

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Ryeznik, Yevgen

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