TY - JOUR
T1 - Sequential balancing
T2 - A simple method for treatment allocation in clinical trials
AU - Borm, George Florimond
AU - Hoogendoorn, Elizabeth H.
AU - Den Heijer, Martin
AU - Zielhuis, Gerhard A.
PY - 2005/12
Y1 - 2005/12
N2 - Although minimisation methods have frequently been advocated for treatment allocation in clinical trials, they are not widely used. As this may partly be due to the complexity of the methods, we devised a new and simple minimisation method to balance for prognostic factors, called sequential balancing. Each factor is dealt with sequentially and when a new subject enters the trial, he or she is allocated the treatment that leads to improved balance of the first factor over the treatments. If the balance of the first factor was already satisfactory, then the treatment is allocated that leads to improved balance of the second factor and so on. The algorithm requires no calculations. We simulated a realistic trial and compared the performance of this method to the performance of alternative allocation strategies: the variance minimisation method, simple randomisation and stratification. The sequential balancing method led to better balance than randomisation and stratification. In the case of four factors or less, the performance of the sequential balancing method and the variance minimisation method were comparable and the sequence of the factors was not very relevant. When more factors were introduced, the balance of the sequential method remained comparable with the balance achieved with the variance minimisation method for the first four factors, but it started to decrease from the fifth factor onwards. We conclude that the ease and simplicity of the new method make it an attractive option when balance is required for four factors or less. If there are more than four factors, the sequential balancing method may still be an acceptable option, but the advantage of simplicity has to be weighed against the loss of performance compared to other minimisation methods.
AB - Although minimisation methods have frequently been advocated for treatment allocation in clinical trials, they are not widely used. As this may partly be due to the complexity of the methods, we devised a new and simple minimisation method to balance for prognostic factors, called sequential balancing. Each factor is dealt with sequentially and when a new subject enters the trial, he or she is allocated the treatment that leads to improved balance of the first factor over the treatments. If the balance of the first factor was already satisfactory, then the treatment is allocated that leads to improved balance of the second factor and so on. The algorithm requires no calculations. We simulated a realistic trial and compared the performance of this method to the performance of alternative allocation strategies: the variance minimisation method, simple randomisation and stratification. The sequential balancing method led to better balance than randomisation and stratification. In the case of four factors or less, the performance of the sequential balancing method and the variance minimisation method were comparable and the sequence of the factors was not very relevant. When more factors were introduced, the balance of the sequential method remained comparable with the balance achieved with the variance minimisation method for the first four factors, but it started to decrease from the fifth factor onwards. We conclude that the ease and simplicity of the new method make it an attractive option when balance is required for four factors or less. If there are more than four factors, the sequential balancing method may still be an acceptable option, but the advantage of simplicity has to be weighed against the loss of performance compared to other minimisation methods.
KW - Balance
KW - Clinical trial
KW - Minimisation
KW - Randomisation
KW - Subject allocation
UR - http://www.scopus.com/inward/record.url?scp=28344447732&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cct.2005.09.002
DO - https://doi.org/10.1016/j.cct.2005.09.002
M3 - Article
C2 - 16226925
SN - 1551-7144
VL - 26
SP - 637
EP - 645
JO - Contemporary clinical trials
JF - Contemporary clinical trials
IS - 6
ER -