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Comparative Study
. 2024 Oct;20(10):6834-6843.
doi: 10.1002/alz.14160. Epub 2024 Aug 13.

Standardized statistical framework for comparison of biomarkers: Techniques from ADNI

Danielle J Harvey  1 , Duygu Tosun  2   3 , Clifford R Jack Jr  4 , Michael Weiner  2   3   5   6   7 , Laurel A Beckett  1 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations
Comparative Study

Standardized statistical framework for comparison of biomarkers: Techniques from ADNI

Danielle J Harvey et al. Alzheimers Dement. 2024 Oct.

Abstract

Introduction: Well-chosen biomarkers have the potential to increase the efficiency of clinical trials and drug discovery and should show good precision as well as clinical validity.

Methods: We suggest measures that operationalize these criteria and describe a general approach that can be used for inference-based comparisons of biomarker performance. The methods are applied to measures obtained from structural magnetic resonance imaging (MRI) from individuals with mild dementia (n = 70) or mild cognitive impairment (MCI; n = 303) enrolled in the Alzheimer's Disease Neuroimaging Initiative.

Results: Ventricular volume and hippocampal volume showed the best precision in detecting change over time in both individuals with MCI and with dementia. Differences in clinical validity varied by group.

Discussion: The methodology presented provides a standardized framework for comparison of biomarkers across modalities and across different methods used to generate similar measures and will help in the search for the most promising biomarkers.

Highlights: A framework for comparison of biomarkers on pre-defined criteria is presented. Criteria for comparison include precision in capturing change and clinical validity. Ventricular volume has high precision in change for both dementia and mild cognitive impairment (MCI) trials. Imaging measures' performance in clinical validity varies more for dementia than for MCI.

Keywords: ADNI; biomarker comparison; clinical validity; precision.

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Conflict of interest statement

Drs. Harvey, Tosun, and Beckett receive research funding from the National Institutes of Health (NIH). Dr. Harvey serves as a Statistical Advisor for PLOS ONE. Dr. Weiner serves on editorial boards for Alzheimer's & Dementia, Magnetic Resonance Imaging and Topics in Magnetic Resonance Imaging. He has served on advisory boards for Acumen Pharmaceutical, Alzheimer's Disease Neuroimaging Initiative (ADNI), Alzheon, Inc., Biogen, Brain Health Registry, Cerecin, Dolby Family Ventures, Eli Lilly, Merck Sharp & Dohme Corp., National Institute on Aging (NIA), Nestle/Nestec, Patient‐Centered Outcomes Research Institute /Patient Partnered Research Network (PCORI/PPRN), Roche, University of Southern California (USC), and NervGen. He has provided consulting to Baird Equity Capital, BioClinica, Cerecin, Inc., Cytox, Dolby Family Ventures, Duke University, Eisai, FUJIFILM‐Toyama Chemical (Japan), Garfield Weston, Genentech, Guidepoint Global, Indiana University, Japanese Organization for Medical Device Development, Inc. (JOMDD), Medscape, Nestle/Nestec, NIH, Peerview Internal Medicine, Roche, T3D Therapeutics, USC, and Vida Ventures. He has acted as a speaker/lecturer to The Buck Institute for Research on Aging, China Association for Alzheimer's Disease (CAAD), Japan Society for Dementia Research, and Korean Dementia Society. He holds stock options with Alzheon, Inc., Alzeca, and Anven. The following entities have provided funding for academic travel: USC, NervGen, American Society of Functional Neuroradiology (ASFNR), and Clinical Trials on Alzheimer's Disease (CTAD) Congress. Dr. Jack is employed by Mayo Clinic. He receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Author disclosures are available in the supporting information.

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