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. 2024 Jun;20(6):4331-4341.
doi: 10.1002/alz.13785. Epub 2024 May 6.

Generating real-world evidence in Alzheimer's disease: Considerations for establishing a core dataset

James E Galvin  1 , Jeffrey L Cummings  2 , Mihaela Levitchi Benea  3 , Carl de Moor  4 , Ricardo F Allegri  5   6 , Alireza Atri  7   8   9 , Howard Chertkow  10 , Claire Paquet  11 , Verna R Porter  12   13 , Craig W Ritchie  14 , Sietske A M Sikkes  15   16 , Michael R Smith  4 , Christina Marsica Grassi  4 , Ivana Rubino  4
Affiliations

Generating real-world evidence in Alzheimer's disease: Considerations for establishing a core dataset

James E Galvin et al. Alzheimers Dement. 2024 Jun.

Abstract

Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real-world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here, we share considerations for observational postapproval studies designed to collect harmonized longitudinal data from individuals with mild cognitive impairment or mild dementia stage of disease who receive therapies targeting the underlying pathological processes of AD in routine practice. This paper considers key study design parameters, including proposed aims and objectives, study populations, approaches to data collection, and measures of cognition, functional abilities, neuropsychiatric status, quality of life, health economics, safety, and drug utilization. Postapproval studies that capture these considerations will be important to provide standardized data on AD treatment effectiveness and safety in real-world settings.

Keywords: Alzheimer's disease; core outcomes; data collection; population; real‐world evidence; study aims.

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Conflict of interest statement

J.E.G.: Provided consultation to Alpha Cognition, Biogen, Cognition Therapeutics, CND Life Sciences, EIP Pharma, Eisai, Eli Lilly, GE Healthcare, Genentech, Otsuka, and Roche. J.E.G. is the Chief Scientific Officer for Cognivue, the creator of the Quick Dementia Rating System, and holds the copyright with the New York University Grossman School of Medicine. J.E.G. is supported by National Institute on Aging (NIA) grants R01AG071514, R01AG701514S1, R56AG074889, R01AG071643, R01AG069765, R01AG057681, P01AG066584, and P30AG059295 and National Institute of Neurological Disorders and Stroke (NINDS) grants R01NS101483 and R01NS101483S1. J.L.C.: Provided consultation to Acadia, Actinogen, Acumen, AlphaCognition, Aprinoia, AriBio, Artery, Biogen, BioVie, Cassava, Cerecin, Diadem, EIP Pharma, Eisai, GemVax, Genentech, GAP Innovations, Janssen, Jocasta, Karuna, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Optoceutics, Otsuka, PRODEO, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, Sunbird Bio, Suven, SynapseBio, TrueBinding, Vaxxinity, and Wren Therapeutics pharmaceutical, assessment, and investment companies. J.L.C. is supported by National Institute of General Medical Sciences grant P20GM109025; NINDS grant U01NS093334; NIA grants R01AG053798, P20AG068053, P30AG072959, and R35AG71476; Alzheimer's Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment; and the Joy Chambers‐Grundy Endowment. M.L.B., C.deM., C.M.G., and M.R.S.: During the development of the study protocol and development of the manuscript, they were employees of Biogen and may hold stock, but have since left the company. I.R. is an employee of Biogen and may hold stock. R.F.A.: Supported by grants from Alzheimer's Association, CONICET (Consejo Nacional de Investigaciones Científicas y Tecnológicas de Argentina), Fleni Foundation, and subcontract funding from NIH (R01AGO53267). R.F.A. has served as a consultant or principal investigator for Bago, Biogen, Merck, Novo‐Nordisk, and Roche. A.A.: Received honoraria for consulting, participated in independent data safety monitoring boards, provided educational lectures, programs, and materials, and served on advisory boards for AbbVie, Acadia, Allergan, Alzheimer's Association, Alzheimer's Disease International (ADI), Axovant, AZ Therapies, Biogen, Eisai, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Lundbeck, Merck, Prothena, Roche/Genentech, Novo Nordisk, Qynapse, Sunovion, Suven, and Synexus. A.A. receives royalties from Oxford University Press for a medical book on dementia and has received institutional grants and contract funding from NIA/NIH 1P30AG072980, AZ DHS CTR040636, Washington University St. Louis, Foundation for NIH (FNIH), and Gates Ventures. A. Atri's institution receives funding for clinical trials, biomarker and observational studies, contracts, and projects from AD consortia, foundations, and companies for which A.A. serves as the site principal investigator (past institution received funding for the Biogen EMERGE study; current institution receiving funding for the Eisai‐sponsored AHEAD 3‐45 study). H.C.: Supported by a foundation grant from Canadian Institutes for Health Research (CIHR), along with the Weston Foundation and the Baycrest Health Sciences Foundation. In the past 5 years, H.C. has participated as a site principal investigator in pharmaceutical trial activities sponsored by Alector LLC, Anavex Life Sciences, Hoffmann‐La Roche Limited, Lilly, TauRx, and Immunocal (site investigator for trials). H.C. participated as an unpaid advisor in 2020/21 for the establishment of an international database by Biogen (ICARE AD). C.P.: Member of the International Advisory Boards of Lilly and a consultant for Ads Neuroscience, AgenT, Alzhois, Euroimmune, Fujirebio, Roche, and Gilead. C.P. is an investigator in several clinical trials for AstraZeneca, Biogen, Esai, Lilly, Lundbeck, Neuroimmune, and Roche. V.R.P.: Provided consultation to Biogen and is supported by grants from the National Institutes of Health, Providence St. Joseph Health (Alzheimer's Translational Pillar [ATP]); Pacific Neuroscience Institute Foundation, including the generous support of the Singleton and McLoughlin families, and Saint John's Health Center Foundation. C.W.R.: Provided consultation to AbbVie, Actinogen, Alchemab Therapeutics, Biogen, Brain Health Scotland, Eisai, Lilly, Merck, Novo Nordisk, Roche, Roche Diagnostics, Signant Health, and Sygnature Discovery and is supported by grants from Biogen, AC Immune SA, and Roche. C.W.R. has intellectual property developed at the University of Edinburgh licensed to Linus Health and is Chief Executive Officer and Founder of Scottish Brain Sciences. S.A.M.S.: Supported by grants from Health∼Holland, Top sector Life Sciences & Health (PPP‐allowance; nos. LSHM20084 and LSHM19051), and ZonMW (nos. 7330502051 and 73305095008). Served as a consultant for Boehringer Ingelheim, Lundbeck, Takeda, and Toyama. S.A.M.S. is the developer and receives license fees for the use of the Amsterdam IADL Questionnaire from Alzheon, Axon Neuroscience, Genentech, Green Valley, Janssen, MedAvante, Roche, Vivoryon, and vTv Therapeutics. All funding, consultancy fees, and license fees are paid to S.A.M. Sikkes’ institution. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Schedule of data collection. *Study information may be collected at any routine clinical visits scheduled per local standard of care. Data from radiological assessments of MRI scans will be collected at each MRI visit. It is expected that after a patient reaches target dosing, information on each patient will be collected at the physician's discretion or as part of routine clinical practice, anticipated to be approximately every 6 to 12 months. AD, Alzheimer's disease; M, month; MRI, magnetic resonance imaging; QoL, quality of life.
See this image and copyright information in PMC

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