Evidence map›Paper›PMID 40621876›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Synthetic control methods for n-of-1 and parallel-group trials in Alzheimer's disease: A proof-of-concept study using the I-CONECT.

Chao-Yi Wu, Liu Chen, John R Dickson, Bo Zhang, Steven E Arnold, Hiroko H Dodge

Registry-linked trialAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report 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 NCT02871921 (Internet-based Conversational Engagement Clinical Trial), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT02871921 nacompletednot on this map

Internet-based Conversational Engagement Clinical Trial

TypeinterventionalSponsorMassachusetts General HospitalRan2018 to 2021Enrolled186ConditionsAging, Mild Cognitive ImpairmentArmsConversational Engagement
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. 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

6 authors.

Chao-Yi WuDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.ORCID 0000-0002-2187-6509
Liu ChenDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
John R DicksonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Bo ZhangDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Steven E ArnoldDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Hiroko H DodgeDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Funding

National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BRADFORD C DICKERSON · 2019 to 2026
$36.5M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PHILIP L DE JAGER · 2020 to 2026
$30.1M
Research Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
NIA NIH HHS K01 AG088184NIA NIH HHS K01AG088184NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG086401NIA NIH HHS P30 AG086404NIA NIH HHS R01 AG051628NIA NIH HHS R01AG051628NIA NIH HHS R01 AG056102NIA NIH HHS R01AG056102NIA NIH HHS R01 AG072449NIA NIH HHS R01 AG079280NIA NIH HHS RF1 AG072449NIA NIH HHS U24 AG072122
6 · The paper itself

Abstract

introductionWith the advent of Alzheimer's disease (AD)-modifying and symptomatic treatments of demonstrated efficacy, enrolling participants as concurrent placebo controls in trials can become increasingly difficult. Synthetic controls have been proposed as a viable alternative to concurrent control groups, but their feasibility and reliability remain untested in AD studies.

methodsI-CONECT trial, which evaluates conversational interactions on cognition, was used to test synthetic control methods. Data from the National Alzheimer's Coordinating Center-Uniform Data Set was used to create synthetic-controls for I-CONECT participants using two methods: 1) case mapping and 2) case modeling. Efficacy estimates were compared between original versus synthetic-controlled trials.

resultsIn parallel-group designs, treatment effect sizes for the primary outcome were closely aligned between the original trial (β = 1.67) and synthetic control analyses (β = 1.40-1.65). For n-of-1 designs, the two methods showed high agreement in identifying treatment responders (Kappa = 0.75-0.82). DISCUSSION: Synthetic control methods are feasible and reliable to create alternative controls in AD studies. CLINICAL

trial registrationNCT02871921. HIGHLIGHTS: Synthetic control methods are feasible and suitable for evaluating treatment effects in various trial designs such as n-of-1, single-arm, and parallel groups. Synthetic control methods can help replicate early-phase Alzheimer's trials, informing go/no-go decisions for larger-scale studies. The choice of similarity algorithms is critical as it affects the quality of historical case mapping. The National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) provided an ideal pool for identifying historical cases with similar demographic, biological, and social characteristics to participants in trials, enabling the creation of synthetic control groups for Alzheimer's clinical research.

Indexed as

Alzheimer DiseaseResearch DesignAgedFemaleHumansMaleProof of Concept StudyReproducibility of ResultsTreatment Outcomealternative trial designcohort studyindividual treatment responsemachine learningNACC‐UDSnatural historypersonalized medicinereplicabilityreproducibilitysimulationtreatment responder

Identifiers

PMID40621876
PMCPMC12230867

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.