{"doi":"10.14283/jpad.2024.112","title":"Clinical Meaningfulness in Alzheimer's Disease Clinical Trials. A Report from the EU-US CTAD Task Force","abstract":"Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer's disease, following several decades of failures. Indeed, all three trials have met their primary endpoints. However, the absolute size of the benefit measured in these trials has generated a debate on whether the change scores observed on clinical outcome assessments represent a clinically meaningful benefit to patients. An evidence-based conclusion is urgently required to inform decision-making related to the approval, reimbursement, and ultimately, the management of emerging therapies in clinical practice. The EU-US CTAD Task Force met in Boston to address this important question. The current state-of-the-art knowledge for interpreting clinical meaningfulness of AD clinical trial results, including the point of view of patients and study partners on what is clinically meaningful, was discussed and is summarized here. A combination of methodologies to address the challenges emerged. There remain gaps in the understanding of clinical meaningfulness that only long-term longitudinal studies will be able to address.","journal":"The Journal of Prevention of Alzheimer s Disease","year":2024,"id":430737,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1015181,"name":"J Cummings","orcid":null,"position":1,"is_corresponding":false},{"id":1234556,"name":"C.J. Lansdall","orcid":null,"position":2,"is_corresponding":false},{"id":1124347,"name":"Lavinia P. Middleton","orcid":"0000-0001-6445-3947","position":3,"is_corresponding":false},{"id":92185,"name":"Cristina Sampaio","orcid":"0000-0002-7052-9079","position":4,"is_corresponding":false},{"id":1234557,"name":"S. Gauthier","orcid":null,"position":5,"is_corresponding":false},{"id":838768,"name":"Sarah Cohen","orcid":"0000-0003-1188-1854","position":6,"is_corresponding":false},{"id":1015189,"name":"R.C. Petersen","orcid":null,"position":7,"is_corresponding":false},{"id":915920,"name":"D.M. Rentz","orcid":null,"position":8,"is_corresponding":false},{"id":650509,"name":"Alette M. Wessels","orcid":null,"position":9,"is_corresponding":false},{"id":226504,"name":"Suzanne Hendrix","orcid":"0000-0002-2374-7727","position":10,"is_corresponding":false},{"id":1234067,"name":"F. Jessen","orcid":"0000-0002-9537-5002","position":11,"is_corresponding":false},{"id":619705,"name":"Marı́a C. Carrillo","orcid":null,"position":12,"is_corresponding":false},{"id":229359,"name":"Rachelle S. Doody","orcid":null,"position":13,"is_corresponding":false},{"id":67390,"name":"Michael C. Irizarry","orcid":null,"position":14,"is_corresponding":false},{"id":1198607,"name":"J. Scott Andrews","orcid":"0009-0001-5516-7719","position":15,"is_corresponding":false},{"id":67333,"name":"Bruno Vellas","orcid":null,"position":16,"is_corresponding":false},{"id":920056,"name":"P. Aisen","orcid":null,"position":17,"is_corresponding":false},{"id":229474,"name":"Sandrine Andrieu","orcid":null,"position":18,"is_corresponding":false},{"id":228359,"name":"Randall J. Bateman","orcid":"0000-0002-7729-1702","position":19,"is_corresponding":false},{"id":671640,"name":"Richard Batrla","orcid":null,"position":20,"is_corresponding":false},{"id":1234558,"name":"Joanne Bell","orcid":null,"position":21,"is_corresponding":false},{"id":1234559,"name":"Oskar Bosson","orcid":null,"position":22,"is_corresponding":false},{"id":1200274,"name":"Sasha Bozeat","orcid":null,"position":23,"is_corresponding":false},{"id":1015072,"name":"Dawn A. Brooks","orcid":null,"position":24,"is_corresponding":false},{"id":838766,"name":"Samantha Budd Haeberlein","orcid":"0000-0002-4824-646X","position":25,"is_corresponding":false},{"id":1199998,"name":"Teresa Buracchio","orcid":null,"position":26,"is_corresponding":false},{"id":426517,"name":"Min Cho","orcid":"0000-0003-4696-0173","position":27,"is_corresponding":false},{"id":1234560,"name":"Matthew Choung","orcid":null,"position":28,"is_corresponding":false},{"id":1234561,"name":"Gavin Cook","orcid":null,"position":29,"is_corresponding":false},{"id":1234562,"name":"Darrin Crisitello","orcid":null,"position":30,"is_corresponding":false},{"id":1234068,"name":"Fernando Dangond","orcid":"0000-0002-6723-4229","position":31,"is_corresponding":false},{"id":842646,"name":"Susan De Santi","orcid":"0000-0002-1902-1202","position":32,"is_corresponding":false},{"id":1234563,"name":"Ellen B. Dennehy","orcid":null,"position":33,"is_corresponding":false},{"id":67374,"name":"Shobha Dhadda","orcid":null,"position":34,"is_corresponding":false},{"id":1234564,"name":"Harjeet K. Dhillon","orcid":null,"position":35,"is_corresponding":false},{"id":1198608,"name":"Billy Dunn","orcid":"0000-0002-4314-5993","position":36,"is_corresponding":false},{"id":304918,"name":"Michael Egan","orcid":"0000-0002-9709-1206","position":37,"is_corresponding":false},{"id":990186,"name":"Fiona Elwood","orcid":"0000-0002-4354-920X","position":38,"is_corresponding":false},{"id":1234565,"name":"Sven Eriksson","orcid":null,"position":39,"is_corresponding":false},{"id":1234566,"name":"Tom Fagan","orcid":null,"position":40,"is_corresponding":false},{"id":263964,"name":"Howard Fillit","orcid":"0000-0002-3509-6706","position":41,"is_corresponding":false},{"id":1234567,"name":"Per‐Ola Freskgård","orcid":null,"position":42,"is_corresponding":false},{"id":1234568,"name":"Diana Gallagher","orcid":null,"position":43,"is_corresponding":false},{"id":1234569,"name":"Gopi Gangi","orcid":null,"position":44,"is_corresponding":false},{"id":1234570,"name":"Carlos Granda","orcid":null,"position":45,"is_corresponding":false},{"id":1234069,"name":"David Greeley","orcid":"0000-0003-2811-3835","position":46,"is_corresponding":false},{"id":1234571,"name":"Anna-Kaija Gronblad","orcid":null,"position":47,"is_corresponding":false},{"id":282617,"name":"Harald Hampel","orcid":"0000-0003-0894-8982","position":48,"is_corresponding":false},{"id":1234572,"name":"Paul Hawthorne","orcid":null,"position":49,"is_corresponding":false},{"id":1234573,"name":"David Henley","orcid":null,"position":50,"is_corresponding":false},{"id":1234574,"name":"Joe Herring","orcid":null,"position":51,"is_corresponding":false},{"id":1234575,"name":"Steve Hersch","orcid":null,"position":52,"is_corresponding":false},{"id":1234576,"name":"Bill Holt","orcid":null,"position":53,"is_corresponding":false},{"id":55002,"name":"Takeshi Iwatsubo","orcid":"0000-0003-1160-8129","position":54,"is_corresponding":false},{"id":1234070,"name":"Daryl Jones","orcid":"0000-0002-6446-3595","position":55,"is_corresponding":false},{"id":1177347,"name":"Anja Kahl","orcid":null,"position":56,"is_corresponding":false},{"id":1234071,"name":"Gene G. Kinney","orcid":"0009-0004-8649-4175","position":57,"is_corresponding":false},{"id":74385,"name":"Hartmuth C. Kolb","orcid":"0000-0003-2414-5792","position":58,"is_corresponding":false},{"id":842885,"name":"Lynn D. Kramer","orcid":null,"position":59,"is_corresponding":false},{"id":1234072,"name":"Luka Kulic","orcid":"0000-0003-3427-9436","position":60,"is_corresponding":false},{"id":792364,"name":"Sanjay Kumar","orcid":"0000-0002-0937-918X","position":61,"is_corresponding":false},{"id":877250,"name":"Lars Lannfelt","orcid":"0000-0001-9839-659X","position":62,"is_corresponding":false},{"id":611065,"name":"John A. Lawson","orcid":"0000-0002-9814-3039","position":63,"is_corresponding":false},{"id":1234577,"name":"Valérie Legrand","orcid":null,"position":64,"is_corresponding":false},{"id":1234578,"name":"Rachel Lenington","orcid":null,"position":65,"is_corresponding":false},{"id":279149,"name":"Frank M. Longo","orcid":"0000-0002-9514-7325","position":66,"is_corresponding":false},{"id":480301,"name":"Brandy R. Matthews","orcid":null,"position":67,"is_corresponding":false},{"id":66434,"name":"Donna Masterman","orcid":null,"position":68,"is_corresponding":false},{"id":1234579,"name":"Kristina A. McLinden","orcid":null,"position":69,"is_corresponding":false},{"id":1234580,"name":"Sarah Mikels","orcid":null,"position":70,"is_corresponding":false},{"id":536972,"name":"Michael J. Miller","orcid":"0000-0002-6026-6279","position":71,"is_corresponding":false},{"id":229365,"name":"Mark A. Mintun","orcid":null,"position":72,"is_corresponding":false},{"id":868941,"name":"Hans J. Moebius","orcid":"0000-0002-6311-0157","position":73,"is_corresponding":false},{"id":1234073,"name":"Cecília Monteiro","orcid":"0000-0001-8109-5395","position":74,"is_corresponding":false},{"id":21809,"name":"Mario A. Morken","orcid":null,"position":75,"is_corresponding":false},{"id":482511,"name":"Jennifer Murphy","orcid":"0000-0003-3101-8951","position":76,"is_corresponding":false},{"id":1234581,"name":"Tomas Odergren","orcid":null,"position":77,"is_corresponding":false},{"id":1234074,"name":"Gunilla Osswald","orcid":"0000-0003-3620-7161","position":78,"is_corresponding":false},{"id":1234582,"name":"Laura Parnas","orcid":null,"position":79,"is_corresponding":false},{"id":1234583,"name":"Maria‐Magdalena Patru","orcid":null,"position":80,"is_corresponding":false},{"id":1234075,"name":"Charlene M. Prazma","orcid":"0000-0001-8455-4788","position":81,"is_corresponding":false},{"id":226625,"name":"Rema Raman","orcid":"0000-0002-4096-6390","position":82,"is_corresponding":false},{"id":1234584,"name":"Larisa Reyderman","orcid":null,"position":83,"is_corresponding":false},{"id":1234585,"name":"Sharon Rogers","orcid":null,"position":84,"is_corresponding":false},{"id":1234586,"name":"Lise Roman","orcid":null,"position":85,"is_corresponding":false},{"id":67520,"name":"Gary Romano","orcid":null,"position":86,"is_corresponding":false},{"id":617009,"name":"Mark Roskey","orcid":null,"position":87,"is_corresponding":false},{"id":1224275,"name":"Ivana Rubino","orcid":null,"position":88,"is_corresponding":false},{"id":66423,"name":"Laurie Ryan","orcid":null,"position":89,"is_corresponding":false},{"id":301881,"name":"Stephen Salloway","orcid":"0000-0002-2631-0942","position":90,"is_corresponding":false},{"id":67662,"name":"Rachel Schindler","orcid":null,"position":91,"is_corresponding":false},{"id":226069,"name":"Lon S. Schneider","orcid":"0000-0002-1875-3735","position":92,"is_corresponding":false},{"id":465765,"name":"David Scott","orcid":"0000-0001-5226-1972","position":93,"is_corresponding":false},{"id":618063,"name":"John R. Sims","orcid":"0009-0009-0168-9050","position":94,"is_corresponding":false},{"id":505435,"name":"Daniel Skovronsky","orcid":null,"position":95,"is_corresponding":false},{"id":892033,"name":"Marion Soto","orcid":"0000-0001-6825-3985","position":96,"is_corresponding":false},{"id":1212804,"name":"Reisa Sperling","orcid":null,"position":97,"is_corresponding":false},{"id":67533,"name":"Lennert Steukers","orcid":null,"position":98,"is_corresponding":false},{"id":668060,"name":"Erik Stoops","orcid":"0000-0001-9989-4486","position":99,"is_corresponding":false},{"id":1234066,"name":"Davide Angioni","orcid":"0000-0003-3253-2522","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:59:20.861374Z","pmid":"39350367","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}