Evidence map›Paper›PMID 41122812›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Seeking optimal repeated fluid biomarker assessments to enhance precision and statistical power in clinical trials: SLIM method.

Hiroko H Dodge, Liu Chen, Chao-Yi Wu, Gary Cutter, Gene L Bowman, Howard H Feldman, Steven E Arnold

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07236190 (Early-phase Biomarker-based Trial of NPC-1 for Alzheimer's Disease Pathology), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT07236190 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Early-phase Biomarker-based Trial of NPC-1 for Alzheimer's Disease Pathology

TypeinterventionalSponsorMassachusetts General HospitalRan2026 to 2027Enrolled40ConditionsAlzheimer Disease, Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD)Armsnatural product combination-1 (NPC1)
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

7 authors.

Hiroko H DodgeDepartment of Neurology, Interdisciplinary Brain Center, Massachusetts General Brigham, Harvard Medical School, Charlestown, Massachusetts, USA.
Liu ChenDepartment of Neurology, Interdisciplinary Brain Center, Massachusetts General Brigham, Harvard Medical School, Charlestown, Massachusetts, USA.
Chao-Yi WuDepartment of Neurology, Interdisciplinary Brain Center, Massachusetts General Brigham, Harvard Medical School, Charlestown, Massachusetts, USA.
Gary CutterSchool of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Gene L BowmanDepartment of Neurology, McCance Center for Brain Health, Massachusetts General Brigham, Harvard Medical School, Somerville, Massachusetts, USA.
Howard H FeldmanSan Diego School of Medicine, Alzheimer's Disease Cooperative Study at the University of California, La Jolla, California, USA.
Steven E ArnoldDepartment of Neurology, Interdisciplinary Brain Center, Massachusetts General Brigham, Harvard Medical School, Charlestown, Massachusetts, USA.

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KEVIN M DUFF, Lisa C Silbert · 2020 to 2026
$28.6M
NIA NIH HHS P30 AG062421NIA NIH HHS P30AG062421NIA NIH HHS P30 AG066518the Epstein Family Collaboration of Powder for Pennies
6 · The paper itself

Abstract

introductionPlasma biomarkers are increasingly used as surrogate outcomes in clinical trials for Alzheimer's disease and related dementias (ADRD) due to their non-invasive nature. In early-phase trials designed to evaluate mechanisms of action and biological efficacy, assessing pre-post changes in plasma biomarkers within the same individuals - using a single-arm placebo lead-in design - offers a potentially cost-effective alternative to parallel-group designs by minimizing between-subject variability. However, plasma biomarkers are also subject to within-individual variability, which can obscure true treatment effects.

methodsOne strategy to address this limitation is to collect repeated measures during each study period. This approach can improve measurement precision, enhance the signal-to-noise ratio, and increase statistical power, even with modest sample sizes.

resultsWe propose an innovative early-phase trial design, Single-arm Lead-In with Multiple measures (SLIM), which incorporates repeated biomarker assessments over a short follow-up period. DISCUSSION: Using simulation studies, we demonstrate that the SLIM design can substantially reduce required sample sizes. HIGHLIGHTS: SLIM involves repeated biomarker assessments during both the lead-in and post-treatment periods. It minimizes between-subject variability and improves the precision of within-subject estimates. It is well suited for early-phase, short-duration trials. It is not suitable for cognitive tests or other outcomes prone to practice or placebo effects. SLIM design can be an alternative to the traditional parallel design by reducing required sample sizes, thereby lowering the recruitment burden.

Indexed as

Alzheimer DiseaseBiomarkersClinical Trials as TopicResearch DesignComputer SimulationHumansBiomarkersbetween‐individual variabilityclinical trialplasma biomarkersSingle‐arm Lead‐In with Multiple measures (SLIM)statistical powerwithin‐individual variability

Identifiers

PMID41122812
PMCPMC12541280

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Registered trials

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.