Modelling the patient accrual with truncated Gaussian mixture distribution for the accurate estimation of sample size in survival trials

Abstract

In survival trials with fixed trial length, the patient accrual rate has a significant impact on the sample size estimation or equivalently, on the power of trials. A larger sample size is required for the staggered patient entry. During enrollment, the patient accrual rate changes with the recruitment publicity effect, disease incidence and many other factors and fluctuations of the accrual rate occur frequently. However, the existing accrual models are either over-simplified for the constant rate assumption or complicated in calculation for the subdivision of the accrual period. A more flexible accrual model is required to represent the fluctuant patient accrual rate for accurate sample size estimation. In this paper, inspired by the flexibility of the Gaussian mixture distribution in approximating continuous densities, we propose the truncated Gaussian mixture distribution accrual model to represent different variations of accrual rate by different parameter configurations. The sample size calculation formula and the parameter setting of the proposed accrual model are discussed further.