Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force.

Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.

Déclaration de conflit d'intérêts

The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work. D. Angioni is an investigator in clinical trials sponsored by Roche, Alector, Jansen, Alzheon, Otsuka, Novonordisk, UCB Pharma, Medesis Pharma and Eisai. No direct personal benefit is to be declared. J. Delrieu has received payment/honoraria from Biogen (presentation for Biogen in 2021); has participated on a Data Safety Monitoring Board or Advisory Board for French board for Roche in 2020-2022. H. Fillit is an unpaid consultant to Lilly and Biogen. He have received consulting fees from Alector, Samus Therapeutics, TauRx, Pinteon, Otsuka/Lundbeck, and Genentech during the past 3 years. P. Aisen reports grants from Janssen, NIA, FNIH, Alzheimer’s Association, Eisai and consultant fees from Merck, Biogen, Roche, ImmunoBrain Checkpoint, Abbvie, Rainbow Medical, Shionogi, Vigil Neuroscience, Inc, Hengrui USA, outside the submitted work. J. Cummings reports grants from: NIGMS grant P20GM109025; NINDS grant U01NS093334; NIA grant R01AG053798; NIA grant P20AG068053; NIA grant P30AG072959; NIA grant R35AG71476; Alzheimer’s Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment for the Pam Quirk Brain Health and Biomarker Laboratory; and the Joy Chambers-Grundy Endowment during the conduct of the study. J. Cummings receives consultant fees from AB Science, Acadia, Alkahest, AlphaCognition, ALZPathFinder, Annovis, AriBio, Artery, Avanir, Biogen, Biosplice, Cassava, Cerevel, Clinilabs, Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, VigilNeuro pharmaceutical, assessment, and investment companies, outside the submitted work. J. Cummings is the Chief Scientific Officer for CNS Innovations, LLC. J.R. Sims is an employee of Eli Lilly and Company: salary and minor stockholder. J. Braunstein is Employee of C2N Diagnostics. M. Sabbagh. Ownership interest (stock or stock options): NeuroTau, Optimal Cognitive Health Company, uMethod Health, Versanum, Athira, TransDermix, Seq BioMarque, NeuroReserve, Cortexyme/Quince Therapeutics; Consulting: Alzheon, Roche-Genentech, Eisai, KeifeRx, Lilly, Synaptogenix, NeuroTherapia, T3D, Signant Health, Novo Nordisk; Royalties: Humanix; Board of Director: Cortexyme/Quince Therapeutics, EIP Pharma. T. Bittner is a full time employee of F.Hoffmann-LaRoche AG and Genentech. M. Pontecorvo is an employee of Avid Radiopharmaceuticals, a wholly owned affiliate of Eli Lilly and Corporation and is a minor stockholder in Lilly. S. Bozeat is a full-time employee of Hoffman-La Roche and has stock options in the company. J.L. Dage is an inventor on patents or patent applications of Eli Lilly and Company relating to the assays, methods, reagents and/or compositions of matter related to measurement of P-tau217. Dr. Dage has served as a consultant for Genotix Biotechnologies Inc, Gates Ventures, Karuna Therapeutics, AlzPath Inc, Cognito, and received research support from ADx Neurosciences, Roche Diagnostics and Eli Lilly and Company in the past two years. E. Largent reports grants from National Institute on Aging, grants from Greenwall Foundation, outside the submitted work. S. Mattke reports personal fees from Biogen, Eisai, Roche/Genentech, Novartis, C2N, outside the submitted work. D.R. Willis is the principal investigator on a grant funded by the Devos Alzheimer’s Collaborative. This grant provides travel to the DAC in-person meetings. D.R. Willis did not participate or consume any food provided by industry partners. The DAC includes in-kind contributions from industry partners for patients to complete digital cognitive assessments (no charge for software or hardware) and blood-based biomarkers testing (sample processing). Contractual relationships between her university and each industry partner offering those in-kind resources (Linus Health and C2N Diagnostics respectively) prevent any undue influence over any scholarly work or dissemination related to the project. At the time of submission of this paper, they did not have sent any specimen to C2N for in-kind processing. To date no financial benefit has been received from C2N. Alireza Atri has received honoraria or support for consulting; participating in independent data safety monitoring boards; providing educational lectures, programs, and materials; or serving on advisory boards for AbbVie, Acadia, Allergan, the Alzheimer’s Association, Axovant, AZ Therapies, Biogen, Eisai, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Lundbeck, Merck, Roche/Genentech, Novo Nordisk, Qynapse, Sunovion, Suven, and Synexus. Dr. Atri receives book royalties from Oxford University Press for a medical book on dementia. Dr. Atri currently receives institutional research grant/contract funding from NIA/NIH 1P30AG072980, AZ DHS CTR040636, Washington University St Louis, and Gates Ventures. Dr. Atri’s institution receives/received funding for clinical trial grants, contracts and projects from government, consortia, foundations and companies for which he serves/served as contracted site-PI. Washington University and R.J. Bateman have equity ownership interest in C2N Diagnostics and receive income based on technology (blood plasma assay) licensed by Washington University to Diagnostics. R.J. Bateman receives income from C2N Diagnostics for serving on the scientific advisory board. Washington University, with R.J. Bateman as co-inventor, has submitted the US nonprovisional patent application “Plasma Based Methods for Determining A-Beta Amyloidosis.” R.J. Bateman has received honoraria as a speaker/consultant/advisory board member from Amgen, Eisai, Hoffman-LaRoche, and Janssen; and reimbursement of travel expenses from, Hoffman-La Roche and Janssen. As an investigator, P.J. Ousset has received research funding from the following companies: Acadia Pharmaceuticals, Alector Inc., Alzheon Inc., Araclon Biotech S.L., AstraZeneca, Biogen, Avanir Pharmaceuticals, Cortexyme Inc., Eisai Inc., Eli Lilly, Genentech, Inc., Hoffmann-La Roche, Janssen Research and Development, Merck Sharp and Dohme, Novartis Pharmaceuticals, Novo Nordisk, Shanghai Green Valley Pharmaceutical Co., TauRx Therapeutics Ltd, UCB Biopharma. No direct personal benefit is to be declared. B. Vellas is an investigator in clinical trials sponsored by Biogen, Lilly, Roche, Eisai Pharmaceuticals and the Toulouse University Hospital. He has served as SAB member for Biogen, Alzheon, Green Valley, Norvo Nordisk, Longeveron, but received no personal compensation. He has served as consultant and/or SAB member for Roche, Lilly, Eisai, TauX with personal compensation. He is member of the Editorial Board of JPAD with no personal compensation; and did not have a role in the editorial process/review for this manuscript. M. Weiner reports serves on Editorial Boards for Alzheimer’s and Dementia, MRI and TMRI. He has served on Advisory Boards for Acumen Pharmaceutical, ADNI, Alzheon, Inc., Biogen, Brain Health Registry, Cerecin, Dolby Family Ventures, Eli Lilly, Merck Sharp and Dohme Corp., National Institute on Aging (NIA), Nestle/Nestec, PCORI/PPRN, Roche, University of Southern California (USC), 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, University of Southern California (USC), WebMD, 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; University of Southern California (USC), NervGen, ASFNR, and CTAD Congres. Mr. Weiner receives support for his research from the following funding sources: Ðational Institutes of Health (NIH), Department of Defense (DOD), Patient-Centered Outcomes Research Institute (PCORI), California Department of Public Health (CDPH), University of Michigan, Siemens, Biogen, Hillblom Foundation, Alzheimer’s Association, The State of California, Johnson and Johnson, Kevin and Connie Shanahan, GE, VUmc, Australian Catholic University (HBI-BHR), The Stroke Foundation, and the Veterans Administration