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  • Key words Multiple sclerosis  (2)
  • Magnetic resonance imaging  (1)
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  • 1
    ISSN: 1432-1920
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effect of consensus formation and training on the agreement between observers in scoring the number of new and enlarging multiple sclerosis (MS) lesions on serial T2-weighted MRI studies. The baseline and month 9 MRI studies of 16 patients with a range of MRI activity were used (dual-echo conventional spin-echo sequence, TR 2000, TE 34 and 90 ms, 5 mm contiguous slices, in-plane resolution 1 mm). First, the serial studies were visually analysed for the presence of new and enlarging lesions, on two occasions, by five experienced observers, without adopting any consensus strategy and in isolation. Next, the observers met to identify the common sources of inconsistencies in reporting between observers and formulate consensus rules. Finally, a further independent reading session was performed on the same MRI dataset, this time applying the consensus rules. Agreement between observers was assessed using kappa scores. Without the consensus rules, interobserver kappa scores for the first and second reading sessions for new lesions were only 0.51 and 0.39 respectively; agreement for enlarging lesions was even worse. The mean intraobserver kappa score for new lesions was higher at 0.72, reflecting the fact that the observers were consistently applying their individual assessment strategies. Application of the consensus rules did not lead to a significant improvement in inter observer kappas; the kappa scores adopting the guidelines were 0.46 and 0.21 for new and enlarging lesions respectively. Consensus guidelines thus did not improve the reproducibility of visual analysis of serial T2-weighted MRI, and the level of agreement between observers remained only moderate. Suboptimal repositioning is likely to be a major source of residual variability and this suggests a future role for image registration strategies; until then, a single observer, or pair of observers working in consensus, should be used in MS studies.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Treatment trial ; Power calculations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR) or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process.
    Type of Medium: Electronic Resource
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