TY - JOUR
T1 - Merged block randomisation
T2 - A novel randomisation procedure for small clinical trials
AU - van der Pas, Stéphanie L.
N1 - Funding Information: This work was supported by a grant by KiKa project number 275. Publisher Copyright: © The Author(s) 2019. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Background/Aims: Randomisation in small clinical trials is a delicate matter, due to the tension between the conflicting aims of balanced groups and unpredictable allocations. The commonly used method of permuted block randomisation has been heavily criticised for its high predictability. This article introduces merged block randomisation, a novel and conceptually simple restricted randomisation design for small clinical trials (less than 100 patients per stratum). Merged block randomisation is a simple procedure that can be carried out without need for a computer. Merged block randomisation is not restricted to 1:1 randomisation, but is readily applied to unequal target allocations and to more than two treatment groups. Methods: The position of merged block randomisation on the spectrum of balance and predictability is investigated in a simulation study, in two common situations: a single-centre study and a multicentre study (with sampling stratified per centre). Methods included for comparison were permuted block randomisation, Efron’s biased coin design, the maximal procedure, the block urn design and the big stick design. Results: Compared to permuted block randomisation with blocks of size 4, merged block randomisation has the same maximum tolerated imbalance and is thus as impervious to chronological bias, with the added benefit of being less predictable. Each method in the study takes a different position on the balance/determinism spectrum, and none was uniformly best. Merged block randomisation was either less predictable or more balanced than the other methods, in all simulation settings. Conclusion: Merged block randomisation is a versatile restricted randomisation method that outperforms permuted block randomisation and is a good choice for small clinical trials where imbalance is a main concern, especially in multicentre trials where the number of patients per centre may be small.
AB - Background/Aims: Randomisation in small clinical trials is a delicate matter, due to the tension between the conflicting aims of balanced groups and unpredictable allocations. The commonly used method of permuted block randomisation has been heavily criticised for its high predictability. This article introduces merged block randomisation, a novel and conceptually simple restricted randomisation design for small clinical trials (less than 100 patients per stratum). Merged block randomisation is a simple procedure that can be carried out without need for a computer. Merged block randomisation is not restricted to 1:1 randomisation, but is readily applied to unequal target allocations and to more than two treatment groups. Methods: The position of merged block randomisation on the spectrum of balance and predictability is investigated in a simulation study, in two common situations: a single-centre study and a multicentre study (with sampling stratified per centre). Methods included for comparison were permuted block randomisation, Efron’s biased coin design, the maximal procedure, the block urn design and the big stick design. Results: Compared to permuted block randomisation with blocks of size 4, merged block randomisation has the same maximum tolerated imbalance and is thus as impervious to chronological bias, with the added benefit of being less predictable. Each method in the study takes a different position on the balance/determinism spectrum, and none was uniformly best. Merged block randomisation was either less predictable or more balanced than the other methods, in all simulation settings. Conclusion: Merged block randomisation is a versatile restricted randomisation method that outperforms permuted block randomisation and is a good choice for small clinical trials where imbalance is a main concern, especially in multicentre trials where the number of patients per centre may be small.
KW - Restricted random allocation
KW - chronological bias
KW - merged block randomisation
KW - permuted block randomisation
KW - selection bias
KW - small clinical trials
KW - stratified randomisation
UR - http://www.scopus.com/inward/record.url?scp=85061651676&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/1740774519827957
DO - https://doi.org/10.1177/1740774519827957
M3 - Article
C2 - 30761907
SN - 1740-7745
VL - 16
SP - 246
EP - 252
JO - Clinical Trials
JF - Clinical Trials
IS - 3
ER -