Statistical power of MRI monitored trials in multiple sclerosis: new data and comparison with previous results
- aNeuroimaging Research Unit, Department of Neuroscience, Scientific Institute Ospedale San Raffaele, University of Milan, Milan, Italy, bUnit of Clinical Epidemiology and Trials, National Institute for Cancer Research, Genoa, Italy, cNMR Research Unit, Institute of Neurology, London, UK, dDepartment of Neurology, University “La Sapienza”, Rome, Italy, eDutch MS/MR Center, Free University Hospital, Amsterdam, The Netherlands, fDepartment of Neuroradiology, University of Munich, Munich, Germany
- Dr Massimo Filippi, Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Telephone 0039 2 2643 3033; Fax 0039 2 2643 3031; email filippi.massimo{at}hsr.it.
- Received 7 May 1998
- Revised 17 September 1998
- Accepted 14 October 1998
Abstract
OBJECTIVES To evaluate the durations of the follow up and the reference population sizes needed to achieve optimal and stable statistical powers for two period cross over and parallel group design clinical trials in multiple sclerosis, when using the numbers of new enhancing lesions and the numbers of active scans as end point variables.
METHODS The statistical power was calculated by means of computer simulations performed using MRI data obtained from 65 untreated relapsing-remitting or secondary progressive patients who were scanned monthly for 9 months. The statistical power was calculated for follow up durations of 2, 3, 6, and 9 months and for sample sizes of 40–100 patients for parallel group and of 20–80 patients for two period cross over design studies. The stability of the estimated powers was evaluated by applying the same procedure on random subsets of the original data.
RESULTS When using the number of new enhancing lesions as the end point, the statistical power increased for all the simulated treatment effects with the duration of the follow up until 3 months for the parallel group design and until 6 months for the two period cross over design. Using the number of active scans as the end point, the statistical power steadily increased until 6 months for the parallel group design and until 9 months for the two period cross over design. The power estimates in the present sample and the comparisons of these results with those obtained by previous studies with smaller patient cohorts suggest that statistical power is significantly overestimated when the size of the reference data set decreases for parallel group design studies or the duration of the follow up decreases for two period cross over studies.
CONCLUSIONS These results should be used to determine the duration of the follow up and the sample size needed when planning MRI monitored clinical trials in multiple sclerosis.
