Atrophy outcomes in multicentre clinical trials on Alzheimer's disease: effect of different processing and analysis approaches on sample sizes.
Standard
Atrophy outcomes in multicentre clinical trials on Alzheimer's disease: effect of different processing and analysis approaches on sample sizes. / Teipel, Stefan J; Peters, Oliver; Heuser, Isabella; Jessen, Frank; Maier, Wolfgang; Froelich, Lutz; Arlt, Sönke; Hüll, Michael; Gertz, Hermann-Josef; Kornhuber, Johannes; Wiltfang, Jens; Thome, Johannes; Rienhoff, Otto; Meindl, Thomas; Hampel, Harald; Grothe, Michel.
in: WORLD J BIOL PSYCHIA, Jahrgang 12 Suppl 1, 2011, S. 109-113.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Atrophy outcomes in multicentre clinical trials on Alzheimer's disease: effect of different processing and analysis approaches on sample sizes.
AU - Teipel, Stefan J
AU - Peters, Oliver
AU - Heuser, Isabella
AU - Jessen, Frank
AU - Maier, Wolfgang
AU - Froelich, Lutz
AU - Arlt, Sönke
AU - Hüll, Michael
AU - Gertz, Hermann-Josef
AU - Kornhuber, Johannes
AU - Wiltfang, Jens
AU - Thome, Johannes
AU - Rienhoff, Otto
AU - Meindl, Thomas
AU - Hampel, Harald
AU - Grothe, Michel
PY - 2011
Y1 - 2011
N2 - Structural MRI markers may serve as surrogate endpoints in clinical trials on disease modification in Alzheimer's disease (AD). Here, we used a longitudinal MRI data set of total brain and cortical grey matter volumes from 66 patients with AD recruited across seven centres of the German Dementia Competence Network. We compared effect size estimates for the detection of a 25% reduction of atrophy progression between a priori segmentation of brain tissue, implementing an anatomical model of brain tissue distribution, and a posteriori segmentation that was not informed by an anatomical model. Additionally, we compared effect size estimates between fixed effects analysis and a mixed effects model, implementing a random effects term to account for variable spacing of observation times. A priori segmentation reduced the required sample size by 50%. Introducing a random effects term for time led to an additional 50% reduction of required samples sizes compared to fixed effects analysis. In summary, using a priori segmentation with mixed effects analysis reduced the sample size to detect clinically relevant treatment effects more than fourfold. The implementation of mixed effects models will enhance the power to detect treatment effects also with other classes of biological endpoints including molecular biomarkers of disease.
AB - Structural MRI markers may serve as surrogate endpoints in clinical trials on disease modification in Alzheimer's disease (AD). Here, we used a longitudinal MRI data set of total brain and cortical grey matter volumes from 66 patients with AD recruited across seven centres of the German Dementia Competence Network. We compared effect size estimates for the detection of a 25% reduction of atrophy progression between a priori segmentation of brain tissue, implementing an anatomical model of brain tissue distribution, and a posteriori segmentation that was not informed by an anatomical model. Additionally, we compared effect size estimates between fixed effects analysis and a mixed effects model, implementing a random effects term to account for variable spacing of observation times. A priori segmentation reduced the required sample size by 50%. Introducing a random effects term for time led to an additional 50% reduction of required samples sizes compared to fixed effects analysis. In summary, using a priori segmentation with mixed effects analysis reduced the sample size to detect clinically relevant treatment effects more than fourfold. The implementation of mixed effects models will enhance the power to detect treatment effects also with other classes of biological endpoints including molecular biomarkers of disease.
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Longitudinal Studies
KW - Disease Progression
KW - Sample Size
KW - Atrophy
KW - Models, Anatomic
KW - Mental Status Schedule
KW - Brain/pathology
KW - Image Processing, Computer-Assisted
KW - Magnetic Resonance Imaging
KW - Alzheimer Disease/pathology
KW - Cerebral Cortex/pathology
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Longitudinal Studies
KW - Disease Progression
KW - Sample Size
KW - Atrophy
KW - Models, Anatomic
KW - Mental Status Schedule
KW - Brain/pathology
KW - Image Processing, Computer-Assisted
KW - Magnetic Resonance Imaging
KW - Alzheimer Disease/pathology
KW - Cerebral Cortex/pathology
M3 - SCORING: Journal article
VL - 12 Suppl 1
SP - 109
EP - 113
JO - WORLD J BIOL PSYCHIA
JF - WORLD J BIOL PSYCHIA
SN - 1562-2975
ER -
