Format

Send to

Choose Destination
Neurology. 2013 Oct 1;81(14):1215-21. doi: 10.1212/WNL.0b013e3182a6cb9b. Epub 2013 Aug 21.

Clinical and MRI activity as determinants of sample size for pediatric multiple sclerosis trials.

Author information

1
From the Pediatric Demyelinating Disease Program (L.H.V.), Program in Neuroscience & Mental Health, The Hospital for Sick Children, University of Toronto, Canada; Biostatistics Unit (A.S., M.P.S.), Department of Health Sciences, University of Genova, Italy; Department of Neurology & Neurosurgery (D.L.A., A.B.-O.), Montreal Neurological Institute and Hospital, McGill University, Montreal; Department of Neurology and Division of Medical Genetics (A.D.S.), University of British Columbia, Vancouver; Departments of Internal Medicine and Community Health Sciences (R.A.M.), Winnipeg Health Sciences Centre, University of Manitoba, Winnipeg, Canada; and Division of Neurology (B.B.), Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania.

Abstract

OBJECTIVE:

To estimate sample sizes for pediatric multiple sclerosis (MS) trials using new T2 lesion count, annualized relapse rate (ARR), and time to first relapse (TTFR) endpoints.

METHODS:

Poisson and negative binomial models were fit to new T2 lesion and relapse count data, and negative binomial time-to-event and exponential models were fit to TTFR data of 42 children with MS enrolled in a national prospective cohort study. Simulations were performed by resampling from the best-fitting model of new T2 lesion count, number of relapses, or TTFR, under various assumptions of the effect size, trial duration, and model parameters.

RESULTS:

Assuming a 50% reduction in new T2 lesions over 6 months, 90 patients/arm are required, whereas 165 patients/arm are required for a 40% treatment effect. Sample sizes for 2-year trials using relapse-related endpoints are lower than that for 1-year trials. For 2-year trials and a conservative assumption of overdispersion (ϑ), sample sizes range from 70 patients/arm (using ARR) to 105 patients/arm (TTFR) for a 50% reduction in relapses, and 230 patients/arm (ARR) to 365 patients/arm (TTFR) for a 30% relapse reduction. Assuming a less conservative ϑ, 2-year trials using ARR require 45 patients/arm (60 patients/arm for TTFR) for a 50% reduction in relapses and 145 patients/arm (200 patients/arm for TTFR) for a 30% reduction.

CONCLUSION:

Six-month phase II trials using new T2 lesion count as an endpoint are feasible in the pediatric MS population; however, trials powered on ARR or TTFR will need to be 2 years in duration and will require multicentered collaboration.

PMID:
23966255
PMCID:
PMC3795606
DOI:
10.1212/WNL.0b013e3182a6cb9b
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center