Abstract

The advanced analytic methodology for modelling and predicting stochastic processes describing the behaviour in time of different stages in Phase III multicentre clinical trials is discussed. A statistical methodology for predictive patient’s recruitment modelling is developed in [1,2,4] where the patient’s flows are modelled by using Poisson processes with random delays and gamma distributed rates (Poisson-gamma model). ML and Bayesian techniques for estimating parameters and asymptotic approximations for the mean and predictive bounds in time for the number of patients recruited in the regions and for time to complete trial are developed. The optimal number of clinical centres and trial performance can be also evaluated. Analytic technique for predicting in time the number of different events in trials with waiting time to response is developed [5]. The closed-form expressions for predictive distributions are derived and used in oncology trials. Analytic technique for predicting in time randomisation processes in centres/regions is developed and the impact of stratification on sample size is investigated [3,4]. A risk-based supply modelling tool based on these results is developed [2]. Software tools in R supporting these techniques are created. These tools are implemented on R&D GSK level and already led to significant benefits and cost savings.

References

1. Anisimov, V.V., Fedorov, V.V., Modeling, prediction and adaptive adjustment of recruitment in multicentre trials. Statistics in Medicine, v. 26, No. 27, 2007, pp. 4958-4975.

2. Anisimov, V.V., Predictive modelling of recruitment and drug supply in multicenter clinical trials. Proc. of the Joint Statistical Meeting, Washington, USA , August, 2009, pp. 1248-1259.

3. Anisimov, V.V., Effects of unstratified and centre-stratified randomization in multicentre clinical trials. Pharmaceutical Statistics, v. 10, iss. 1, 2011, pp. 50-59.

4. Anisimov, V.V., Statistical modeling of clinical trials (recruitment and randomization), Communications in Statistics – Theory and Methods, 40: 19-20, 2011, pp. 3684-3699.

5. Anisimov, V.V., Predictive event modelling in multicentre clinical trials with waiting time to response, Pharmaceutical Statistics, v. 10, iss. 6, 2011, pp. 517-522.