Evidence map›Paper›PMID 42644414›Full record

ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Estimating treatment effects in clinical studies of Alzheimer's disease: What are estimands and why do we need them?

Suzanne Hendrix, Craig Mallinckrodt, Rikke Mortensen Abschneider, Alireza Atri, Mette Dahl Bendtsen, Teresa Leon Colombo, Howard H Feldman, Peter Johannsen, Jeffrey Cummings

Abstract readReview
In one paragraph

Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Suzanne HendrixPentara Corporation, Millcreek, Utah, USA.ORCID https://orcid.org/0000-0002-2374-7727
Craig MallinckrodtPentara Corporation, Millcreek, Utah, USA.
Rikke Mortensen AbschneiderNovo Nordisk A/S, Søborg, Denmark.
Alireza AtriBanner Sun Health Research Institute, Sun City, Arizona, USA.
Mette Dahl BendtsenNovo Nordisk A/S, Søborg, Denmark.
Teresa Leon ColomboNovo Nordisk A/S, Søborg, Denmark.
Howard H FeldmanAlzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, La Jolla, San Diego, California, USA.
Peter JohannsenNovo Nordisk A/S, Søborg, Denmark.
Jeffrey CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, Nevada, USA.

Funding

Novo Nordisk
6 · The paper itself

Abstract

In clinical studies, it is scientifically important, and a regulatory expectation, that objectives be translated into key clinical questions by specifically defining treatment effects to be estimated. Estimands are part of a structured framework, as presented in International Council for Harmonisation (ICH) E9(R1), by which study objectives are linked to a suitable study design and tools for estimation. Estimands are constructed using five attributes: treatment, population, variable (or endpoint), population-level summary for the variable, and intercurrent events (ICEs). ICEs occur after treatment initiation and can affect the existence or interpretation of the measurements. In Alzheimer's disease (AD), potential ICEs include additional AD medication use, discontinuation of treatment, and death. We describe estimands in recent clinical studies of anti-amyloid therapies, including gantenerumab, lecanemab, and donanemab, in AD and use the evoke and evoke+ studies of semaglutide in early-stage symptomatic AD as examples of estimand application in AD trials.

Indexed as

Alzheimer DiseaseClinical Trials as TopicResearch DesignAntibodies, Monoclonal, HumanizedHumansSemaglutideTreatment OutcomeAntibodies, Monoclonal, HumanizedgantenerumabSemaglutideAlzheimer's diseaseclinical trialsestimandssemaglutidetreatment effect

Identifiers

PMID42644414
PMCPMC13508584

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.