Dōsys

Evidence

Methods and evidence status

What each Dōsys product calculates, which published work it rests on, and which checks have been run. Vancomyzer has not been validated in real patients. Dōsys Parenteral Nutrition is an evaluation release for synthetic adult cases only; it has not completed independent clinical validation and is not for patient care.

Equations and derivationsAbout the PN evaluation release

The population model

Colin 2019, for every adult at every body size.

Vancomyzer uses the two-compartment population pharmacokinetic model published by Colin and colleagues in 2019 [1]: a pooled analysis of 14 studies (2,554 individuals) spanning neonates to elderly adults. Clearance is built from a typical value and four covariate factors — size, maturation (≈1 in adults), age decline and serum creatinine. Volumes scale with total body weight.

The population estimate can be reproduced from the published equations and the inputs the calculator displays. The Bayesian fit to measured levels uses numerical optimization and cannot be reproduced by hand; its method, prior widths and error model are documented on the equations page.

CL (L/h) = 5.31 × (WT/70)^0.75 × FMat × FDecline × FSCR
V1 (L)   = 42.9 × (WT/70)
V2 (L)   = 41.7 × (WT/70)
Q  (L/h) = 3.22 × (WT/70)^0.75

FSCR = exp(−0.649 × (SCr − SCRstd)), SCr in mg/dL
Typical adult (35 y, 70 kg, SCr 0.83): CL ≈ 4.10 L/h

Scope: adults 18 years and older receiving intermittent IV vancomycin who are not on renal replacement therapy. Two published covariates are not applied: hematological malignancy (+29.4% clearance in the published model) is not captured as an input, and heel-prick sampling is neonatal.

Renal function

Serum creatinine, used directly.

Serum creatinine enters the Colin 2019 model directly, compared with an age-standardized reference creatinine. Cockcroft-Gault does not enter the population estimate. After a fit to measured levels, the calculator caps fitted clearance at twice the estimated creatinine clearance; this cap is a calculator design choice, not part of the published model. Cockcroft-Gault values are otherwise shown for context only.

All creatinine-based estimates can overstate renal function when muscle mass is low or renal function is changing. Measured levels entered into the Bayesian fit let the estimate move away from the population prediction.

Body size

No model switch at any BMI.

Colin 2019 is used at every body size, including BMI 40 kg/m² and above; clearance and volumes scale with total body weight as published. There is no threshold at which a different model takes over, so an estimate never jumps because a patient crossed a BMI cut-off.

Published evaluation of the model at BMI ≥ 40 is limited (15 of 49 obese adults [3]), so at that body size the calculator adds an advisory recommending early vancomycin levels. Fat-free mass [7] and alternative creatinine-clearance estimates are shown for information only and do not change the calculation.

The guideline

What it does and does not say.

The 2020 ASHP/IDSA/PIDS/SIDP consensus guideline [2] recommends AUC-guided monitoring for serious MRSA infections, preferably with Bayesian estimation, targeting AUC₂₄ 400–600 mg·h/L (assuming MIC 1 mg/L), citing data associating AUC-guided dosing with less acute kidney injury than trough-guided dosing. Vancomyzer uses that target.

The guideline is not an endorsement of any product. Published evidence for AUC-guided dosing in general — for example Hall 2024 [4], a single-center retrospective cohort using a different Bayesian product — says nothing about Vancomyzer’s accuracy. No claim is made that Vancomyzer reduces kidney injury, improves treatment outcomes or outperforms another dosing product.

What has been checked

Each row links to the full record.

ItemWhat it coversStatus
Population modelColin 2019 two-compartment model; every equation and constant publishedPublished
Literature reproducibilityPublished vancomycin cases run through the calculator; same-model cases are pass/failDeveloper-run
Predictive performance200 synthetic ICU patients from a different published model; one held-out concentration eachDeveloper-run
Comparison with TucuxiSame prior and simulated levels given to a separately built program, scored against pre-set criteriaDeveloper-run
Independent clinical validationRetrospective and prospective evaluation with patient data at a participating institutionPending
FDA reviewDesigned to meet non-device CDS criteria, FD&C §520(o)(1)(E); not reviewed by the FDANot reviewed

“Developer-run” identifies checks designed and performed by the software’s author using published values or simulated patients. These are not independent clinical validation.

Parenteral nutrition

Evaluation release; synthetic cases only.

Dōsys Parenteral Nutrition is an evaluation release for synthetic adult cases only. It has software tests but has not completed independent clinical review, and it is not for patient care. Its calculations follow ASPEN, ESPEN, SCCM, NICE and ISMP frameworks and product labeling, and show the framework behind each suggestion where guidelines disagree. How the evaluation release is built.

Regulatory status

Not FDA-cleared or approved.

Vancomyzer™

A clinical decision-support tool for qualified healthcare professionals only. Designed to meet the non-device clinical decision support criteria of FD&C Act §520(o)(1)(E), added by section 3060 of the 21st Century Cures Act [8]; not reviewed by the FDA. It has not been evaluated in prospective clinical outcome studies.

Dōsys Parenteral Nutrition

An evaluation release for synthetic adult cases only. Not for patient care. Regulatory status depends on each software function, its intended use and the jurisdiction; transparency and clinician involvement do not by themselves establish an exemption.

This page does not establish FDA clearance or a non-device determination. See the medical disclaimer.

References

Numbered as cited above.

  1. 1

    Colin PJ, Allegaert K, Thomson AH, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58(6):767–780.

    doi:10.1007/s40262-018-0727-5

    The population model used in Vancomyzer.

  2. 2

    Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review. Am J Health-Syst Pharm. 2020;77(11):835–864.

    doi:10.1093/ajhp/zxaa036

    Source of the AUC₂₄ 400–600 mg·h/L target. Recommends AUC-guided monitoring, preferably with Bayesian estimation. Not an endorsement of any product.

  3. 3

    Colin PJ, et al. External evaluation of population pharmacokinetic models of vancomycin in obese adults. Ther Drug Monit. 2021;43(1):126–130. PMID 33278242.

    49 obese adults, 15 with BMI ≥ 40. Colin 2019 performed best among the models compared; the cohort is small.

  4. 4

    Hall NM, Brown ML, Edwards WS, et al. Model-informed precision dosing improves outcomes in patients receiving vancomycin for gram-positive infections. Open Forum Infect Dis. 2024;11(1):ofae002.

    doi:10.1093/ofid/ofae002

    Single-center retrospective cohort, n = 300, using a different Bayesian product: desirable outcome 58.7% vs 46.7%, vancomycin-associated AKI 21.3% vs 32.0%, median stay 10 vs 12 days with AUC-guided therapy. Context for AUC-guided dosing; not evidence about Vancomyzer.

  5. 5

    Smit C, De Hoogd S, Brüggemann RJM, Knibbe CAJ. Population pharmacokinetics of vancomycin in obesity: finding the optimal dose for (morbidly) obese individuals. Br J Clin Pharmacol. 2020;86(2):303–317.

    doi:10.1111/bcp.14144

    Documented as a comparator on the literature-reproducibility page; not implemented.

  6. 6

    Zhang T, Scholten JN, Brüggemann RJM, et al. How to dose vancomycin in overweight and obese patients with varying renal (dys)function. Clin Pharmacokinet. 2024;63:79–91.

    doi:10.1007/s40262-023-01324-5

    Documented as a comparator; not implemented.

  7. 7

    Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051–1065.

    doi:10.2165/00003088-200544100-00004

    Fat-free mass shown for information at BMI ≥ 40; not a dosing covariate.

  8. 8

    United States Congress. 21st Century Cures Act, Section 3060 — Clinical Decision Support Software. Public Law 114-255; 2016.

    Source

    The statutory criteria Vancomyzer is designed to meet. The FDA has made no determination.

Questions about a method? Contact Mario.