Pooling Alzheimer's Disease Clinical Trial Data to Develop Personalized Medicine Approaches is Easier Said Than Done: A Proof-of-principle Study and Call to Action

Overview

Journal Alzheimers Dement (N Y)

Date 2024 Aug 8

PMID 39114370

Authors

Mark A Dubbelman

Eleonora M Vromen

Betty M Tijms

Johannes Berkhof

Lois Ottenhoff

Everard G B Vijverberg

Niels D Prins

Wiesje M van der Flier

Sietske A M Sikkes

Affiliations

Soon will be listed here.

Abstract

Highlights: Pooling data from past Alzheimer's disease clinical trials may help identify subgroups most likely to benefit from specific treatments and may help inform future trial design.Accessing past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals.We urge trial sponsors and the academic research community to remove data access barriers and improve collaboration through practicing open science and harmonizing outcome measures.

References

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

Prinsen C, Vohra S, Rose M, Boers M, Tugwell P, Clarke M . How to select outcome measurement instruments for outcomes included in a "Core Outcome Set" - a practical guideline. Trials. 2016; 17(1):449. PMC: 5020549. DOI: 10.1186/s13063-016-1555-2. View

Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M . An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2:S33-9. View

Cummings J, Lee G, Zhong K, Fonseca J, Taghva K . Alzheimer's disease drug development pipeline: 2021. Alzheimers Dement (N Y). 2021; 7(1):e12179. PMC: 8145448. DOI: 10.1002/trc2.12179. View

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen C . Alzheimer's disease. Lancet. 2021; 397(10284):1577-1590. PMC: 8354300. DOI: 10.1016/S0140-6736(20)32205-4. View

Tijms B, Gobom J, Reus L, Jansen I, Hong S, Dobricic V . Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics. Brain. 2021; 143(12):3776-3792. PMC: 7805814. DOI: 10.1093/brain/awaa325. View

Sims J, Zimmer J, Evans C, Lu M, Ardayfio P, Sparks J . Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023; 330(6):512-527. PMC: 10352931. DOI: 10.1001/jama.2023.13239. View

Badhwar A, McFall G, Sapkota S, Black S, Chertkow H, Duchesne S . A multiomics approach to heterogeneity in Alzheimer's disease: focused review and roadmap. Brain. 2020; 143(5):1315-1331. PMC: 7241959. DOI: 10.1093/brain/awz384. View

ROSEN W, Mohs R, Davis K . A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984; 141(11):1356-64. DOI: 10.1176/ajp.141.11.1356. View

10.

Ringman J, Goate A, Masters C, Cairns N, Danek A, Graff-Radford N . Genetic heterogeneity in Alzheimer disease and implications for treatment strategies. Curr Neurol Neurosci Rep. 2014; 14(11):499. PMC: 4162987. DOI: 10.1007/s11910-014-0499-8. View

11.

Brantner C, Nguyen T, Tang T, Zhao C, Hong H, Stuart E . Comparison of methods that combine multiple randomized trials to estimate heterogeneous treatment effects. Stat Med. 2024; 43(7):1291-1314. PMC: 11086055. DOI: 10.1002/sim.9955. View

12.

Bangdiwala S, Bhargava A, OConnor D, Robinson T, Michie S, Murray D . Statistical methodologies to pool across multiple intervention studies. Transl Behav Med. 2016; 6(2):228-35. PMC: 4927450. DOI: 10.1007/s13142-016-0386-8. View

13.

Karpen S, White J, Mullin A, ODoherty I, Hudson L, Romero K . Effective Data Sharing as a Conduit for Advancing Medical Product Development. Ther Innov Regul Sci. 2021; 55(3):591-600. PMC: 7780909. DOI: 10.1007/s43441-020-00255-8. View

14.

Dubbelman M, Hendriksen H, Harrison J, Vijverberg E, Prins N, Kroeze L . Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups. Neurology. 2024; 102(2):e207978. PMC: 10962908. DOI: 10.1212/WNL.0000000000207978. View

15.

Chen P, Yao H, Tijms B, Wang P, Wang D, Song C . Four Distinct Subtypes of Alzheimer's Disease Based on Resting-State Connectivity Biomarkers. Biol Psychiatry. 2022; 93(9):759-769. DOI: 10.1016/j.biopsych.2022.06.019. View

16.

McDade E, Cummings J, Dhadda S, Swanson C, Reyderman L, Kanekiyo M . Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022; 14(1):191. PMC: 9768996. DOI: 10.1186/s13195-022-01124-2. View

17.

Doody R, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S . A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013; 369(4):341-50. DOI: 10.1056/NEJMoa1210951. View

18.

Sperling R, Rentz D, Johnson K, Karlawish J, Donohue M, Salmon D . The A4 study: stopping AD before symptoms begin?. Sci Transl Med. 2014; 6(228):228fs13. PMC: 4049292. DOI: 10.1126/scitranslmed.3007941. View

19.

Liu Y, Li Z, Ge Q, Lin N, Xiong M . Deep Feature Selection and Causal Analysis of Alzheimer's Disease. Front Neurosci. 2019; 13:1198. PMC: 6872503. DOI: 10.3389/fnins.2019.01198. View

20.

Andreasen N, Simeoni M, Ostlund H, Lisjo P, Fladby T, Loercher A . First administration of the Fc-attenuated anti-β amyloid antibody GSK933776 to patients with mild Alzheimer's disease: a randomized, placebo-controlled study. PLoS One. 2015; 10(3):e0098153. PMC: 4366075. DOI: 10.1371/journal.pone.0098153. View