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Record W3114326816 · doi:10.1002/cpt.2149

Clinical Pharmacogenetics Implementation Consortium Guideline for <i>CYP2D6</i>, <i>OPRM1</i>, and <i>COMT</i> Genotypes and Select Opioid Therapy

2021· article· en· W3114326816 on OpenAlexaff
Kristine R. Crews, Andrew A. Monte, Rachel Huddart, Kelly E. Caudle, Evan D. Kharasch, Andrea Gaedigk, Henry M. Dunnenberger, J. Steven Leeder, John T. Callaghan, Caroline Samer, Teri E. Klein, Cyrine E. Haidar, Sara L. Van Driest, Gualberto Ruaño, Katrin Sangkuhl, Larisa H. Cavallari, Daniel J. Müller, Cynthia A. Prows, Mohamed Nagy, Andrew A. Somogyi, Todd C. Skaar

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2021
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsMental Health Research CanadaUniversity of Toronto
FundersNational Center for Advancing Translational SciencesNational Human Genome Research InstituteNational Institute on Drug AbuseNational Health and Medical Research CouncilNational Institute of General Medical SciencesMedical Research CouncilNational Institutes of Health
KeywordsPharmacogeneticsCYP2D6GuidelineOpioidMedicinePharmacologyGenotypeInternal medicineBiologyGeneticsGeneCytochrome P450

Abstract

fetched live from OpenAlex

Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.

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)0.013
metaresearch head score (Gemma)0.043
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.017
Threshold uncertainty score0.068

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0130.043
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.004
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0030.002
Open science0.0040.002
Research integrity0.0080.007
Insufficient payload (model declined to judge)0.0130.007

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 head0.247
GPT teacher head0.572
Teacher spread0.325 · 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 designNot applicable
Domainnot available
GenreMethods

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

Citations399
Published2021
Admission routes1
Has abstractyes

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