Citations 2
Robustness of automated hippocampal volumetry across magnetic resonance field strengths and repeat images
Wolz, Robin, Schwarz, Adam J. , Yu, Peng , Cole, Patricia E., Rueckert, Daniel , Raunig, David , Hill, David , Initiative, The Alzheimer's Disease Neuroimaging, Jack, Clifford R. , Initiative, The Alzheimer's Disease Neuroimaging
Alzheimer's & Dementia | June 28, 2014 | Volume: 10 | Issue: 4 | Pages: 430
AbstractBackgroundLow HCV has recently been qualified by the European Medicines Agency as a biomarker for enrichment of clinical trials in predementia stages of Alzheimer's disease. For automated methods to meet the necessary regulatory requirements, it is essential they be standardized and their performance be well characterized.MethodsThe within‐image and between‐field strength reproducibility of automated hippocampal volumetry using the Learning Embeddings for Atlas Propagation (or LEAP) algorithm was assessed on 153 Alzheimer's Disease Neuroimaging Initiative subjects.ResultsTests/retests at 1.5 T and 3 T, and a comparison between 1.5 T and 3 T, yielded average unsigned variabilities in HCVs of 1.51%, 1.52%, and 2.68%. A small bias between field strengths (mean signed difference, 1.17%; standard deviation, 3.07%) was observed.ConclusionsThe measured reproducibility characteristics confirm the suitability of using automated magnetic resonance imaging analyses to assess HCVs quantitatively and to represent a fundamental characterization that is critical to meet the regulatory requirements for using hippocampal volumetry in clinical trials and health care.
Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease
Hill, David , Schwarz, Adam J. , Isaac, Maria , Pani, Luca , Vamvakas, Spiros, Hemmings, Robert , Carrillo, María C. , Yu, Peng , Sun, Jia , Boccardi, Marina , Brewer, James B., Brumfield, Martha A., Cantillon, Marc, Cole, Patricia E., Fox, Nick C. , Frisoni, Giovanni B. , Kelleher, Thomas, Luo, Feng , Novak, Gerald , Maguire, Paul, Meibach, Richard C., Patterson, Patricia, Bain, Lisa J. , Raunig, David , Soares, Holly , Suhy, Joyce, Wang, Huanli , Wolz, Robin, Stephenson, Diane , Boccardi, Marina , Frisoni, Giovanni B. , Beckett, Laurel , Jack, Clifford R. , Maguire, Paul, Sampaio, Cristina , Fox, Nick C
Alzheimer's & Dementia | June 28, 2014 | Volume: 10 | Issue: 4 | Pages: 421
AbstractBackgroundRegulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.MethodsThe Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data.ResultsThe literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011.ConclusionsWe summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.