Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in relapsing-remitting multiple sclerosis

B. Healy, P. Valsasina, M. Filippi, R. Bakshi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n=116 and n=26) and one dataset of treated patients with RRMS (n=109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33%, 50% and 90% reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset. Results: The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions. Conclusions: Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.

Original languageEnglish
Pages (from-to)1218-1223
Number of pages6
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume80
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Relapsing-Remitting Multiple Sclerosis
Sample Size
Brain
Therapeutics
Outcome Assessment (Health Care)
White Matter
Gray Matter
Cluster Analysis
Datasets
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery

Cite this

@article{680707583711469499ed19ee6004da59,
title = "Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in relapsing-remitting multiple sclerosis",
abstract = "Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n=116 and n=26) and one dataset of treated patients with RRMS (n=109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33{\%}, 50{\%} and 90{\%} reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset. Results: The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions. Conclusions: Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.",
author = "B. Healy and P. Valsasina and M. Filippi and R. Bakshi",
year = "2009",
month = "11",
doi = "10.1136/jnnp.2008.154732",
language = "English",
volume = "80",
pages = "1218--1223",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "11",

}

TY - JOUR

T1 - Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in relapsing-remitting multiple sclerosis

AU - Healy, B.

AU - Valsasina, P.

AU - Filippi, M.

AU - Bakshi, R.

PY - 2009/11

Y1 - 2009/11

N2 - Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n=116 and n=26) and one dataset of treated patients with RRMS (n=109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33%, 50% and 90% reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset. Results: The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions. Conclusions: Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.

AB - Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n=116 and n=26) and one dataset of treated patients with RRMS (n=109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33%, 50% and 90% reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset. Results: The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions. Conclusions: Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.

UR - http://www.scopus.com/inward/record.url?scp=72249104702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72249104702&partnerID=8YFLogxK

U2 - 10.1136/jnnp.2008.154732

DO - 10.1136/jnnp.2008.154732

M3 - Article

C2 - 19204021

AN - SCOPUS:72249104702

VL - 80

SP - 1218

EP - 1223

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 11

ER -