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Record W2204701188 · doi:10.7554/elife.08351

A meta-analysis of threats to valid clinical inference in preclinical research of sunitinib

2015· review· en· W2204701188 on OpenAlex
Valerie C. Henderson, Nadine Demko, Amanda Hakala, Nathalie MacKinnon, Carole A. Federico, Dean Fergusson, Jonathan Kimmelman

Why this work is in the frame

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

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueeLife · 2015
Typereview
Languageen
FieldMedicine
TopicColorectal Cancer Treatments and Studies
Canadian institutionsOttawa HospitalMcGill University
FundersCanadian Institutes of Health Research
KeywordsSunitinibMeta-analysisInferencePreclinical researchComputational biologyResearch integrityMedicineBioinformaticsBiologyComputer scienceInternal medicineArtificial intelligenceEngineering ethicsCancer

Abstract

fetched live from OpenAlex

Poor study methodology leads to biased measurement of treatment effects in preclinical research. We used available sunitinib preclinical studies to evaluate relationships between study design and experimental tumor volume effect sizes. We identified published animal efficacy experiments where sunitinib monotherapy was tested for effects on tumor volume. Effect sizes were extracted alongside experimental design elements addressing threats to valid clinical inference. Reported use of practices to address internal validity threats was limited, with no experiments using blinded outcome assessment. Most malignancies were tested in one model only, raising concerns about external validity. We calculate a 45% overestimate of effect size across all malignancies due to potential publication bias. Pooled effect sizes for specific malignancies did not show apparent relationships with effect sizes in clinical trials, and we were unable to detect dose-response relationships. Design and reporting standards represent an opportunity for improving clinical inference.

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.

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmaMetaresearchMeta-epidemiology (broad)
Domain: Methods · Genre: Review
About the Canadian research system: no · About a Canadian topic: no
Meta-analysislow
gptMetaresearchMeta-epidemiology (broad)
Domain: Methods · Genre: Review
About the Canadian research system: no · About a Canadian topic: no
Meta-analysismedium
models agreeAgreement compares identical category sets and study designs across arms.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.645
Threshold uncertainty score0.696

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0100.003
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

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.

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

Opus teacher head0.915
GPT teacher head0.702
Teacher spread0.212 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it