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Record W4396646590 · doi:10.1101/2024.05.03.24306669

BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial

2024· preprint· en· W4396646590 on OpenAlexaff
Bethany Torr, Christopher I. Jones, Grace Kavanaugh, Monica Hamill, Sophie Allen, Subin Choi, Alice Garrett, Mikel Valganon-Petrizan, Stephen MacMahon, Lina Yuan, Rosalind Way, Helena Harder, Richard H. Gold, Amy Taylor, Rhian Gabe, Anneke Lucassen, Ranjit Manchanda, Lesley Fallowfield, Valerie Jenkins, Ashu Gandhi, D. Gareth Evans, Andrea L. George, Michael Hubank, Z. Kemp, Stephen Bremner, Clare Turnbull

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsInstitute of Cancer Research
Fundersnot available
KeywordsGermlineGenetic testingOncologyMedicineInternal medicineBreast cancerMedical physicsCancerBiologyGenetics

Abstract

fetched live from OpenAlex

ABSTRACT BACKGROUND Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is an important step in the breast cancer diagnostic pathway. To expand capacity and reduce turnaround time, testing is increasingly offered within ‘mainstream’ oncology services, rather than via referral to clinical genetics. However, mainstream capacity is also stretched, as testing is offered to greater proportions of patients. Novel patient-centred pathways may offer opportunity for improved access. PATIENTS AND METHODS We recruited 1,140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT digital pathway; compromising at-home saliva sampling and consenting, with access to a digital dashboard to complete tasks and a genetic counselling telephone hotline. Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%). The primary outcome was uptake of genetic testing. We also measured patient knowledge, anxiety, and satisfaction, and conducted a healthcare professional survey. RESULTS 1,001 (87.8%) participants progressed to receive their pre-test information and consented to testing. Uptake was higher within participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p=0.002, adjusted for participant age and site). Non-inferiority was observed in relation to all other outcomes evaluated. Usage of the telephone hotline was modest (<20% of participants; 1,441 total minutes, 344 clinical minutes recorded) and, of 37 healthcare professionals surveyed, there was majority agreement that all elements of the pathway were equivalent to current standard-of-care. CONCLUSION Findings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling consultation, and that an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into mainstream breast oncology settings.

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)0.003
metaresearch head score (Gemma)0.008
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0010.001
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0140.001

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 head0.295
Teacher spread0.276 · 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 designRandomized trial
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

Citations1
Published2024
Admission routes1
Has abstractyes

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