Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Autor:	Cash DM; Dementia Research Centre, UCL Queen Square Institute of Neurology, London UK.; UK Dementia Research Institute., Morgan KE; London School of Hygiene and Tropical Medicine, London UK., O'Connor A; Dementia Research Centre, UCL Queen Square Institute of Neurology, London UK., Veale TD; Dementia Research Centre, UCL Queen Square Institute of Neurology, London UK., Malone IB; Dementia Research Centre, UCL Queen Square Institute of Neurology, London UK., Poole T; London School of Hygiene and Tropical Medicine, London UK., Benzinger TL; Department of Radiology. Washington University School of Medicine, St. Louis MO., Gordon BA; Department of Radiology. Washington University School of Medicine, St. Louis MO.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA., Ibanez L; Department of Neurology, Washington University in St Louis, St Louis, MO, USA.; Department of Psychiarty, Washington University in St Louis, St Louis, MO, USA., Li Y; Department of Neurology, Washington University in St Louis, St Louis, MO, USA., Llibre-Guerra JJ; Department of Neurology, Washington University in St Louis, St Louis, MO, USA., McDade E; Department of Neurology, Washington University in St Louis, St Louis, MO, USA., Wang G; Department of Neurology, Washington University in St Louis, St Louis, MO, USA., Chhatwal JP; Brigham and Women's Hospital; Massachusetts General Hospital; Harvard Medical School, Boston, MA., Day GS; Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA., Huey E; Alpert Medical School of Brown University, Department of Psychiatry and Human Behavior, Providence, RI., Jucker M; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Levin J; Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Niimi Y; Unit for early and exploratory clinical development, The University of Tokyo Hospital, Tokyo, Japan., Noble JM; Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, GH Sergievksy Center, Columbia University, New York, NY., Roh JH; Departments of Neurology and Physiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea., Sánchez-Valle R; Alzheimer's disease and other cognitive disorders group. Hospital Clínic de Barcelona. FRCB-IDIBAPS. University of Barcelona, Barcelona, Spain., Schofield PR; Neuroscience Research Australia, Sydney Australia.; School of Biomedical Sciences, University of New South Wales, Sydney Australia., Bateman RJ; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA.; Department of Neurology, Washington University in St Louis, St Louis, MO, USA.; Hope Center for Neurological Disorders, Washington University in St Louis, St Louis, MO, USA., Frost C; London School of Hygiene and Tropical Medicine, London UK., Fox NC; Dementia Research Centre, UCL Queen Square Institute of Neurology, London UK.; UK Dementia Research Institute.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Nov 16. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1101/2024.11.12.24316919
Abstrakt:	Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals. Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Results: Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 22[95%CI 13,46], cortical PIB 32[20,57], CSF p-tau181 58[40,112]) for a four-year trial to have 80% power (5% statistical significance) to detect a 25% reduction in absolute levels of pathology, allowing 40% dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50% reduction in rate of change. Sample sizes ranged from 75-250 (examples precuneus volume: 137[80,284], cortical FDG: 256[100,1208], CDR-SB: 161[102,291]). Discussion: Despite the rarity of ADAD, clinical trials with feasible sample sizes given the number of cases appear possible.
Databáze:	MEDLINE
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