OBJECTIVES: Serial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample size calculations for the RR subgroup are based on the data from small numbers of patients and separate calculations for the SP subgroup have not been performed. The present study considers these issues. METHODS: The sample size calculations were based on data from six months of monthly T2 weighted and gadolinium enhanced MRI in 31 RR and 28 SP untreated patients undergoing natural history studies or in the placebo arm of a therapeutic trial. The calculations were for a placebo controlled, parallel groups design lasting six months. The sample sizes were based on bootstrap analysis with an 80% likelihood of showing a given treatment effect. RESULTS: With a single pretreatment scan, demonstration of a 70% reduction in newly active lesions required 2x30 RR and 2x50 SP patients. With an extra run-in scan one month before treatment, the sample sizes were 2x20 for RR and 2x30 for SP patients. CONCLUSIONS: The sample sizes required for RR patients were comparable with previous smaller studies. Larger sample sizes were needed for the SP group, but the extra run in scan resulted in a reduction in both groups. The larger sample sizes in the SPMS group were probably due to the combination of a higher proportion of patients with low MRI activity (< or =2 active MRI lesions in 50% of SP and 32% RR patients), as well as a few patients who displayed extremely high activity, thus increasing interpatient variability. These data should be considered in planning pilot MRI outcome trials.
RCT Entities:
OBJECTIVES: Serial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample size calculations for the RR subgroup are based on the data from small numbers of patients and separate calculations for the SP subgroup have not been performed. The present study considers these issues. METHODS: The sample size calculations were based on data from six months of monthly T2 weighted and gadolinium enhanced MRI in 31 RR and 28 SP untreated patients undergoing natural history studies or in the placebo arm of a therapeutic trial. The calculations were for a placebo controlled, parallel groups design lasting six months. The sample sizes were based on bootstrap analysis with an 80% likelihood of showing a given treatment effect. RESULTS: With a single pretreatment scan, demonstration of a 70% reduction in newly active lesions required 2x30 RR and 2x50 SPpatients. With an extra run-in scan one month before treatment, the sample sizes were 2x20 for RR and 2x30 for SPpatients. CONCLUSIONS: The sample sizes required for RR patients were comparable with previous smaller studies. Larger sample sizes were needed for the SP group, but the extra run in scan resulted in a reduction in both groups. The larger sample sizes in the SPMS group were probably due to the combination of a higher proportion of patients with low MRI activity (< or =2 active MRI lesions in 50% of SP and 32% RR patients), as well as a few patients who displayed extremely high activity, thus increasing interpatient variability. These data should be considered in planning pilot MRI outcome trials.
Authors: J W Thorpe; D Kidd; I F Moseley; B E Kenndall; A J Thompson; D G MacManus; W I McDonald; D H Miller Journal: Neurology Date: 1996-02 Impact factor: 9.910
Authors: C Isaac; D K Li; M Genton; C Jardine; E Grochowski; M Palmer; L F Kastrukoff; J Oger; D W Paty Journal: Neurology Date: 1988-10 Impact factor: 9.910
Authors: R Rudick; J Antel; C Confavreux; G Cutter; G Ellison; J Fischer; F Lublin; A Miller; J Petkau; S Rao; S Reingold; K Syndulko; A Thompson; J Wallenberg; B Weinshenker; E Willoughby Journal: Ann Neurol Date: 1996-09 Impact factor: 10.422
Authors: A J Thompson; A G Kermode; D Wicks; D G MacManus; B E Kendall; D P Kingsley; W I McDonald Journal: Ann Neurol Date: 1991-01 Impact factor: 10.422
Authors: Adnan H Siddiqui; Robert Zivadinov; Ralph H B Benedict; Yuval Karmon; Jihnhee Yu; Mary L Hartney; Karen L Marr; Vesela Valnarov; Cheryl L Kennedy; Murali Ramanathan; Deepa P Ramasamy; Kresimir Dolic; David W Hojnacki; Ellen Carl; Elad I Levy; L Nelson Hopkins; Bianca Weinstock-Guttman Journal: Neurology Date: 2014-06-27 Impact factor: 9.910
Authors: Radu Tanasescu; Christopher R Tench; Cris S Constantinescu; Gary Telford; Sonika Singh; Nanci Frakich; David Onion; Dorothee P Auer; Bruno Gran; Nikos Evangelou; Yasser Falah; Colin Ranshaw; Cinzia Cantacessi; Timothy P Jenkins; David I Pritchard Journal: JAMA Neurol Date: 2020-09-01 Impact factor: 18.302
Authors: M P Sormani; P D Molyneux; C Gasperini; F Barkhof; T A Yousry; D H Miller; M Filippi Journal: J Neurol Neurosurg Psychiatry Date: 1999-04 Impact factor: 10.154
Authors: M P Sormani; D H Miller; G Comi; F Barkhof; M Rovaris; P Bruzzi; M Filippi Journal: J Neurol Neurosurg Psychiatry Date: 2001-04 Impact factor: 10.154