Randomization in survival studies: An evaluation method that takes into account selection and chronological bias

Marcia Viviane Rückbeil, Ralf-Dieter Hilgers, Nicole Heussen, Marcia Viviane Rückbeil, Ralf-Dieter Hilgers, Nicole Heussen

Abstract

The random allocation of patients to treatments is a crucial step in the design and conduct of a randomized controlled trial. For this purpose, a variety of randomization procedures is available. In the case of imperfect blinding, the extent to which a randomization procedure forces balanced group sizes throughout the allocation process affects the predictability of allocations. As a result, some randomization procedures perform superior with respect to selection bias, whereas others are less susceptible to chronological bias. The choice of a suitable randomization procedure therefore depends on the expected risk for selection and chronological bias within the particular study in question. To enable a sound comparison of different randomization procedures, we introduce a model for the combined effect of selection and chronological bias in randomized studies with a survival outcome. We present an evaluation method to quantify the influence of bias on the test decision of the log-rank test in a randomized parallel group trial with a survival outcome. The effect of selection and chronological bias and the dependence on the study setting are illustrated in a sensitivity analysis. We conclude with a case study to showcase the application of our model for comparing different randomization procedures in consideration of the expected type I error probability.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Influence of the study setting…
Fig 1. Influence of the study setting on the distribution of type I error probabilities.
The distributions are based on a sample of 2,500 randomization sequences per randomization procedure.

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Source: PubMed

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