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Record W4413387568 · doi:10.1016/j.gim.2025.101561

A microcosting and cost consequence analysis from a randomized controlled trial comparing genome sequencing with exome sequencing for genetic diagnosis

2025· article· en· W4413387568 on OpenAlexafffund
Wendy J. Ungar, Vercancy Wu, Christian R. Marshall, Jackie Hwang, Robin Z. Hayeems, Kate Tsiplova, Meredith Gillespie, Anna Szuto, Caitlin Chisholm, Dimitri J. Stavropoulos, Viji Venkataramanan, Bowen Xiao, Gregory Costain, Mélanie Beaulieu Bergeron, Sarah L. Sawyer, Lynette Lau, Lijia Huang, Roberto Mendoza‐Londono, Martin J. Somerville, Kym M Boycott

Bibliographic record

VenueGenetics in Medicine · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsChildren's Hospital of Eastern OntarioHospital for Sick ChildrenInstitute for Clinical Evaluative SciencesSickKids Foundation
FundersEuroQol Research FoundationCanada Excellence Research Chairs, Government of CanadaGenome CanadaCanadian Fertility and Andrology SocietyACMG Foundation for Genetic and Genomic MedicineOntario Ministry of Health and Long-Term CarePharmaceutical Research and Manufacturers of America Foundation
KeywordsExome sequencingExomeRandomized controlled trialDNA sequencingMedicineCancer genome sequencingComputational biologyWhole genome sequencingPersonal genomicsGeneticsGenomeBiologyBioinformaticsMutationGeneInternal medicine

Abstract

fetched live from OpenAlex

PURPOSE: Diagnosing rare diseases is costly. The objectives were to microcost exome (ES) and genome sequencing (GS) trios and estimate the incremental costs of GS per additional diagnosis from an institutional payer perspective. METHODS: Trios (proband plus biological parents) that are referred for sequencing were randomly assigned to ES or GS. Laboratory workflow and sequencing were microcosted. Total and category cost per trio were estimated probabilistically. Effectiveness was expressed as diagnostic yield (rates of diagnostic or partially diagnostic variants detected). Incremental costs and effectiveness were calculated. RESULTS: The mean total cost per trio was CAD 2888.79 (95% CI 2567.72, 3492.72) for ES (n = 329) and 4364.02 (95% CI 3984.94, 5013.67) for GS (n = 324). Reagents accounted for 34% and 61% of total costs for ES and GS, respectively. The incremental cost of GS was 1475.23. The diagnostic yield was 35.9% for ES and 32.7% for GS with a difference of 0.032 (95% CI: -0.041, 0.104, P value .397). CONCLUSION: GS demonstrated higher costs and a similar diagnostic yield to ES but was limited by technical capabilities at the time of the study. The study provides comprehensive costs for the economic evaluation comparing alternative diagnostic pathways and impetus for further evaluating variants uniquely detectable by GS.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.022
metaresearch head score (Gemma)0.037
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.022
Threshold uncertainty score0.115

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0220.037
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0050.013
Bibliometrics0.0020.001
Science and technology studies0.0010.002
Scholarly communication0.0020.002
Open science0.0020.002
Research integrity0.0030.005
Insufficient payload (model declined to judge)0.0150.001

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 head0.019
GPT teacher head0.283
Teacher spread0.264 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreEmpirical

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

Citations2
Published2025
Admission routes2
Has abstractyes

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