Some issues in predicting patient recruitment in multi-centre clinical trials

• Published in: Statistics in medicine 2013-12, Vol.32 (30), p.5458-5468
• Main Authors: Bakhshi, Andisheh, Senn, Stephen, Phillips, Alan
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Binomial Distribution; Clinical trials; Clinical Trials as Topic - methods; Dyspepsia - epidemiology; empirical Bayes; Gamma distribution; Humans; Models, Statistical; Multicenter Studies as Topic - methods; negative binomial distribution; Patient Selection; Patients; Poisson distribution; Predictions
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.5979

A key paper in modelling patient recruitment in multi‐centre clinical trials is that of Anisimov and Fedorov. They assume that the distribution of the number of patients in a given centre in a completed trial follows a Poisson distribution. In a second stage, the unknown parameter is assumed to come from a Gamma distribution. As is well known, the overall Gamma‐Poisson mixture is a negative binomial. For forecasting time to completion, however, it is not the frequency domain that is important, but the time domain and that of Anisimov and Fedorov have also illustrated clearly the links between the two and the way in which a negative binomial in one corresponds to a type VI Pearson distribution in the other. They have also shown how one may use this to forecast time to completion in a trial in progress. However, it is not just necessary to forecast time to completion for trials in progress but also for trials that have yet to start. This suggests that what would be useful would be to add a higher level of the hierarchy: over all trials. We present one possible approach to doing this using an orthogonal parameterization of the Gamma distribution with parameters on the real line. The two parameters are modelled separately. This is illustrated using data from 18 trials. We make suggestions as to how this method could be applied in practice. Copyright © 2013 John Wiley & Sons, Ltd.