Meaningful benefits: A framework to assess disease-modifying therapies in preclinical and early Alzheimer’s disease
Open accessAbstract
BACKGROUND: The need for preventive therapies that interrupt the progression of Alzheimer's disease (AD) before the onset of symptoms or when symptoms are emerging is urgent and has spurred the ongoing development of disease-modifying therapies (DMTs) in preclinical and early AD (mild cognitive impairment [MCI] to mild dementia). Assessing the meaningfulness of what are likely small initial treatment effects in these earlier stages of the AD patho-clinical disease continuum is a major challenge and warrants further consideration. BODY: To accommodate a shift towards earlier intervention in AD, we propose meaningful benefits as a new umbrella concept that encapsulates the spectrum of potentially desirable outcomes that may be demonstrated in clinical trials and other studies across the AD continuum, with an emphasis on preclinical AD and early AD (i.e., MCI due to AD and mild AD dementia). The meaningful benefits framework applies to data collection, assessment, and communication across three dimensions: (1) multidimensional clinical outcome assessments (COAs) including not only core disease outcomes related to cognition and function but also patient- and caregiver-reported outcomes, health and economic outcomes, and neuropsychiatric symptoms; (2) complementary analyses that help contextualize and expand the understanding of COA-based assessments, such as number-needed-to-treat or time-to-event analyses; and (3) assessment of both cumulative benefit and predictive benefit, where early changes on cognitive, functional, or biomarker assessments predict longer-term clinical benefit. CONCLUSION: The concept of meaningful benefits emphasizes the importance of multidimensional reporting of clinical trial data while, conceptually, it advances our understanding of treatment effects in preclinical AD and mild cognitive impairment due to AD. We propose that such an approach will help bridge the gap between the emergence of DMTs and their clinical use, particularly now that a DMT is available for patients diagnosed with MCI due to AD and mild AD dementia.
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DMTs are treatments that postpone, moderate, or even reverse the evolution of an illness by addressing its underlying cause.
“DMTs are treatments that postpone, moderate, or even reverse the evolution of an illness by addressing its underlying cause.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [6]
The time-to-dementia progression analysis and a 'time saved' analysis on the primary endpoint will provide important measures of the clinical meaningfulness of changes observed with semaglutide treatment.
“The time-to-dementia progression analysis and a “time saved” analysis on the primary endpoint will provide important measures of the clinical meaningfulness of changes observed with semaglutide treatment [69–71].”
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Flagged first, then by citations
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Lecanemab: Appropriate Use Recommendations
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Self-citationMachine learning and digital biomarkers can detect early stages of neurodegenerative diseases
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Expectations and clinical meaningfulness of randomized controlled trials
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“These novel strategies aim to both drastically alter the illness’s trajectory and cure its symptoms, which might make a big difference in the battle against this debilitating condition [5,6].”
BackgroundEvaluation of clinical benefits of treatments for Alzheimer's disease
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- Authors
- Assunção, S. S., Sperling, R. A., Ritchie, C., Kerwin, D. R., Aisen, P. S., Lansdall, C., Atri, A., & Cummings, J.
- Affiliations
- Roche (United States) (US)
- Brigham and Women's Hospital (US)
- University of Edinburgh (GB)
- The University of Texas Southwestern Medical Center (US)
- University of Southern California (US)
- F. Hoffmann-La Roche AG (CH)
- University of Nevada, Las Vegas (US)
- Corresponding author
- Assunção, Sheila Seleri
- Venue
- Alzheimer's Research & Therapy
- Published
- 2022-04-19
- Volume
- 14
- Issue
- 1
- Pages
- 54-54
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC9017027
- OpenAlex
- W4224216819
- Cited by
- 71
- References
- 92
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 26 · 2023: 17 · 2022: 4
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Genentech
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
- Keywords
- Alzheimer's disease, disease-modifying therapy, preclinical Alzheimer's disease, early Alzheimer's disease, mild cognitive impairment, mild dementia, clinical outcome assessment, patient-reported outcomes, caregiver-reported outcomes, number needed to treat, neuropsychiatric symptoms, economic outcomes, biomarkers
- MeSH terms
- Alzheimer Disease, Cognition, Dementia, Humans, Disease Progression, Cognitive Dysfunction
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