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Record W2923422267 · doi:10.1101/591289

Multicenter preclinical studies as an innovative method to enhance translation: a systematic review of published studies

2019· review· en· W2923422267 on OpenAlexaff
Victoria Hunniford, Agnes Grudniewicz, Dean Fergusson, Emma Grigor, Casey Lansdell, Manoj M. Lalu

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typereview
Languageen
FieldVeterinary
TopicAnimal testing and alternatives
Canadian institutionsInstitut du Savoir MontfortOttawa HospitalBruyèreUniversity of Ottawa
Fundersnot available
KeywordsGeneralizability theoryMulticenter studyMedicineClinical study designClinical trialResearch designSample size determinationPreclinical researchMedical physicsProtocol (science)PsychologyPathologyAlternative medicineRandomized controlled trialStatistics

Abstract

fetched live from OpenAlex

Abstract Multicenter preclinical studies have been suggested as a method to improve reproducibility, generalizability and potential clinical translation of preclinical work. In these studies, multiple independent laboratories collaboratively conduct a research experiment using a shared protocol. The use of a multicenter design in preclinical experimentation is a recent approach and only a handful of preclinical multicenter studies have been published. Here, we systematically identify, assess and synthesize published preclinical multicenter studies investigating interventions using in vivo models. Synthesized data included study methods/design, basic characteristics, outcomes, and barriers and facilitators. Study risk of bias, completeness of reporting and the degree of collaboration were evaluated using established methods. The database searches identified 3095 citations and 12 studies met inclusion criteria. The multicenter study design was applied across a diverse range of diseases including stroke, heart attack, traumatic brain injury, and diabetes. The median number of centers was 4 (range 2-6) and the median sample size was 135 (range 23-384). Most studies had lower risk of bias and higher completeness of reporting than typically seen in single-centered studies. Only four of the twelve studies produced results consistent with previous single-center studies, highlighting a central concern of preclinical research: irreproducibility and poor generalizability of findings from single laboratories. Our review suggests that multicenter preclinical studies may provide a method to robustly assess therapies prior to considering clinical translation. Registered with PROSPERO CRD42018093986.

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.

How this classification was reachedexpand

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)0.005
metaresearch head score (Gemma)0.011
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.033
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0050.011
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0060.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
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 head0.302
GPT teacher head0.509
Teacher spread0.207 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designSystematic review
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations24
Published2019
Admission routes1
Has abstractyes

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