Randomization with non-uniform allocations: fulfillment time distributions and bias properties

Abstract

This article compares the properties of two balanced randomization schemes with several treatments under non-uniform allocation probabilities. According to the first procedure, the so-called truncated multinomial randomization design, the process employs a given allocation distribution, until a treatment receives its quota of subjects, after which this distribution switches to the conditional distribution for the remaining treatments, and so on. The second scheme, the random allocation rule, selects at random any legitimate assignment of the given number of subjects per treatment. The behavior of these two schemes is shown to be quite different: the truncated multinomial randomization design's assignment probabilities to a treatment turn out to vary over the recruitment period, and its accidental bias can be large, whereas the random allocation rule's this bias is bounded. The limiting distributions of the instants at which a treatment receives the given number of subjects is shown to be that of weighted spacings for normal order statistics with different variances. Formulas for the selection bias of both procedures are also derived.

Keywords:

• Accidental bias
• Clinical trials
• Load balancing
• Multinomial trials
• Probability generating function
• Selection bias
• Spacings

Acknowledgements

This research was supported by NSA Grant #H98230-06-1-0068. Helpful comments of the referee are also acknowledged.

Additional information

Notes on contributors

Andrew L. Rukhin

Email: [email protected]