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A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease

2009· letter· en· 739 citations· W2086572083 on OpenAlex· 10.1212/wnl.0b013e3181c67808

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories
Meta-epidemiology (narrow)
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Randomized trialConsensus signal: Randomized trial
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.137
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Opus teacher head0.069
GPT teacher head0.367
Teacher spread
0.298 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

BACKGROUND: Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD. METHODS: The study enrolled 234 patients, randomly assigned to IV bapineuzumab or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 infusions, 13 weeks apart, with final assessments at week 78. The prespecified primary efficacy analysis in the modified intent-to-treat population assumed linear decline and compared treatment differences within dose cohorts on the Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for Dementia. Exploratory analyses combined dose cohorts and did not assume a specific pattern of decline. RESULTS: No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study "completers" and APOE epsilon4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE epsilon4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms. CONCLUSIONS: Primary efficacy outcomes in this phase 2 trial were not significant. Potential treatment differences in the exploratory analyses support further investigation of bapineuzumab in phase 3 with special attention to APOE epsilon4 carrier status. CLASSIFICATION OF EVIDENCE: Due to varying doses and a lack of statistical precision, this Class II ascending dose trial provides insufficient evidence to support or refute a benefit of bapineuzumab.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Neurology
Topic
Alzheimer's disease research and treatments
Field
Medicine
Canadian institutions
Women's Health Research Institute
Funders
National Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Institute on Alcohol Abuse and AlcoholismU.S. Public Health ServiceNational Institute for Health and Care ResearchPfizer
Keywords
MedicineInternal medicineAsymptomaticPlaceboCognitive declineDementiaPopulationDiseaseGastroenterologyClinical endpointOncologyPathologyClinical trial
Has abstract in OpenAlex
yes