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Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application

The Pharmacogenomics Journal volume 21, pages 691–711 (2021)Cite this article

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Abstract

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.

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Fig. 1: Article evaluation process.
Fig. 2: Published pharmacogenomic articles per perioperative medication by FDA approval year.
Fig. 3: Clinical decision-support summaries for sevoflurane and succinylcholine.

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Funding

This work was supported by National Institutes of Health (NIH)/NIGMS 5T32GM007019-41 (for EHJ and TMT as trainees), NIH/NHGRI 1R01HG009938-01A1 (PHO), by an Innovations Grant from the University of Chicago Medicine Office of Clinical Effectiveness (PHO), and the Benjamin McAllister Research Fellowship (TMT).

Author information

Author notes

  1. Ellie H. Jhun

    Present address: Department of Pharmacogenetics, Base10 Genetics, University of Chicago, Chicago, IL, USA

  2. These authors contributed equally: Brittany A. Borden, Ellie H. Jhun.

Authors and Affiliations

  1. Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA

    Brittany A. Borden, Keith Danahey, Emily Schierer, Mark J. Ratain & Peter H. O’Donnell

  2. Center for Personalized Therapeutics, University of Chicago, Chicago, IL, USA

    Ellie H. Jhun, Tien M. Truong, Mark J. Ratain & Peter H. O’Donnell

  3. Center for Research Informatics, University of Chicago, Chicago, IL, USA

    Keith Danahey

  4. Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA

    Jeffrey L. Apfelbaum, Magdalena Anitescu & Sajid Shahul

  5. Department of Pharmacy, University of Chicago Medicine, Chicago, IL, USA

    Randall Knoebel

  6. Department of Medicine, University of Chicago, Chicago, IL, USA

    Mark J. Ratain & Peter H. O’Donnell

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Contributions

BAB: data acquisition, data analysis, and drafting of paper. EHJ: study conception and design, data acquisition, data analysis, and drafting of paper. KD: data acquisition, data analysis. ES: data acquisition, data analysis. JLA: data analysis. MA: data analysis. RK: data analysis. SS: data analysis. TMT: data analysis. MJR: study conception and design. PHO: study conception and design, data acquisition, data analysis, and drafting of paper.

Corresponding author

Correspondence to Peter H. O’Donnell.

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Competing interests

EHJ is currently an employee of OneOme. MJR is a co-inventor holding patents related to pharmacogenetic diagnostics and receives royalties related to UGT1A1 genotyping outside of this work. All other authors declared no competing interests.

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Borden, B.A., Jhun, E.H., Danahey, K. et al. Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application. Pharmacogenomics J 21, 691–711 (2021). https://doi.org/10.1038/s41397-021-00248-2

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