دورية أكاديمية
Robust markers and sample sizes for multicenter trials of Huntington disease
| العنوان: | Robust markers and sample sizes for multicenter trials of Huntington disease |
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| المؤلفون: | Wijeratne, Peter A., Johnson, Eileanoir B., Eshaghi, Arman, Aksman, Leon, Gregory, Sarah, Johnson, Hans J., Poudel, Govinda R., Mohan, Amrita, Sampaio, Cristina, Georgiou-Karistianis, Nellie, Paulsen, Jane S., Tabrizi, Sarah J., Scahill, Rachael I., the Image-Hd, Predict-Hd Track-Hd investigators, Alexander, Daniel C. |
| بيانات النشر: | John Wiley & Sons |
| سنة النشر: | 2020 |
| المجموعة: | Australian Catholic University: ACU Research Bank |
| الوصف: | Objective The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD. Methods We used 1 postprocessing pipeline to retrospectively analyze T1‐weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT‐HD, TRACK‐HD, and IMAGE‐HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease‐affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers. Results We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers. Interpretation Our findings provide the first cross‐study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trials. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 0364-5134 |
| العلاقة: | https://acuresearchbank.acu.edu.au/item/8vz95/robust-markers-and-sample-sizes-for-multicenter-trials-of-huntington-diseaseTest; https://acuresearchbank.acu.edu.au/download/f15e544c6856bc91040fcf500a5978934d1d2bac9ab5a7e79e708d66c9d30d22/8282135/OA_Wijeratne_2020_Robust_markers_and_sample_sizes_for.pdfTest; https://doi.org/10.1002/ana.25709Test; Wijeratne, Peter A., Johnson, Eileanoir B., Eshaghi, Arman, Aksman, Leon, Gregory, Sarah, Johnson, Hans J., Poudel, Govinda R., Mohan, Amrita, Sampaio, Cristina, Georgiou-Karistianis, Nellie, Paulsen, Jane S., Tabrizi, Sarah J., Scahill, Rachael I., the Image-Hd, Predict-Hd Track-Hd investigators and Alexander, Daniel C. (2020). Robust markers and sample sizes for multicenter trials of Huntington disease. Annals of Neurology. 87(5), pp. 751-762. https://doi.org/10.1002/ana.25709Test |
| DOI: | 10.1002/ana.25709 |
| الإتاحة: | https://doi.org/10.1002/ana.25709Test https://acuresearchbank.acu.edu.au/download/f15e544c6856bc91040fcf500a5978934d1d2bac9ab5a7e79e708d66c9d30d22/8282135/OA_Wijeratne_2020_Robust_markers_and_sample_sizes_for.pdfTest |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.A1DE3FFA |
| قاعدة البيانات: | BASE |
| تدمد: | 03645134 |
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| DOI: | 10.1002/ana.25709 |