Bayesian dosing versus free first-order calculators – what’s the difference?

When deciding to transition to an area under the curve (AUC)-based dosing approach for vancomycin dosing, it is important to understand and evaluate all of the vancomycin dosing tools available and to assess the best approach for you.

The options available currently include Excel-based (homegrown), free online web-based or EHR software embedded first order-kinetics calculators, and Bayesian dosing platforms such as DoseMeRx.

Vancomycin dosing

Vancomycin is one of the most frequently used injectable antibiotics in healthcare. The practice of dosing and monitoring of vancomycin has shifted from making these decisions based on trough levels to a more precise therapeutic measurement known as AUC.

National guidelines released by leading pharmacy and infectious diseases medical societies now recommend dosing and monitoring vancomycin based on AUC, preferably via Bayesian software.¹

The ASHP practice guidelines highlight key advantages to using Bayesian software. ¹ They include:

• more accurate and reliable results for estimating AUC when compared to first-order kinetics and improvement in vancomycin-associated therapeutic care through the rapid obtainment of target AUCs, and
• decreased adverse events due to complications such as acute kidney injury (AKI).

The rapid obtainment of AUCs has a clinical benefit to the patient because the infection is treated with the right dose earlier in the course of their infection.

Comparing Bayesian dosing software and free online tools

Free Online Vancomycin Dosing Calculators

Depending on the size of your hospital and specific needs, you may be considering a free vancomycin dosing tool. The free DoseMeRx vancomycin dosing calculator is one of the few online tools available using Bayesian dosing. It is a simplified version of our platform, designed for single use.

Timothy P. Gauthier PharmD, BCPS-AQ ID from IDStewardship published an article identifying 13 free online vancomycin dosing calculators including a review of their last update, AUC output, and a brief description.

What criteria should be considered when evaluating a free tool vs a Bayesian solution?

The key criteria I would encourage you to consider and address in reviewing each option include:

1. Health system size and solution scalability: do you need multiple pharmacists to be able to access the tool and share patient information across your group?
2. Interoperability requirements: Is integration into your Pharmacy Surveillance Software (PSS) such as VigiLanz/Sentri7/ ILÚM Insight® or your EHR required?
3. Standardization: Does clinical practice across multiple sites and pharmacy teams need to be standardized?
4. Workflow integration and efficiency: Do you want to save patient data and customize the system to accommodate your hospital dosing protocols and guidelines?
5. Security: What is your hospital’s policy and procedures regarding data security and risk utilizing tools online?

What should you evaluate when comparing Bayesian dosing to first order kinetics?

The table below provides a comparison between DoseMeRx and first-order dosing calculation tools that have been developed and are available online, via an Excel spreadsheet, or embedded into an EHR. ²

Parameter	First Order /Calculator Approach	DoseMeRx Bayesian Platform
Applicable across pediatrics and neonates	No	Yes
Applicable to patients receiving intermittent hemodialysis	No	Yes
Applicable to patients who are critically ill or have continuously fluctuating clinical status	No	Yes
Flexibility with the timing of levels	No – Must be timed appropriately otherwise levels are wasted	Yes – DoseMeRx can use levels drawn at any time
Ability to easily switch between pharmacokinetic models	No	Yes
Ability to compare trends across time	No	Yes
Doesn’t require the patient to be at a steady-state before calculating a dose	No	Yes
Can take into account changes in dosing regimens	No	Yes

What are other clinical advantages of DoseMeRx compared to first-order kinetics?

• Calculate AUC with a single level: Traditional first-order (i.e. two point) calculators require a post infusion peak and trough in order to calculate an AUC. With DoseMeRx, an AUC can be calculated with a single drug level.
• Improved accuracy: Bayesian dosing produces more accurate calculations than 2-point calculators in calculating the AUC. This is reiterated by the ASHP guidelines. ¹ They state “The major limitation of (first order kinetics) is that it is not adaptive like the Bayesian approach and can only provide a snapshot of the AUC. As such, this AUC calculation will not be correct if a physiologic change such as renal dysfunction occurs during or after the sampling period. Furthermore, it is extremely difficult to estimate the vancomycin AUC24 (with 2-point kinetics) in patients who receive multiple dosing regimens within a 24-hour period.”

• Less dosing adjustments required: A study conducted by Beth Israel Deaconess Medical Center that was presented at a major infectious diseases meeting found up to 63% of avoidable dose adjustments were made with 2-point, first order calculators. This was much higher when compared to using Bayesian dosing.³

• Stores data for retrieval and analysis: This is beneficial when developing analytic reports that can look at trends, opportunity for improvement, and to support medication use evaluations. This information is suitable for presentation at P &T, Antibiotic Stewardship and Quality Committees.

• Feature rich: DoseMeRx features allows the pharmacist the ability to compare trends across time and simulate different models and evaluate outcomes within seconds.
• Allows for standardization of care across all hospital sites: By having one system available for all pharmacists to use, protocols and procedures can be standardized across all hospitals, allow for consistent care from site to site.

• Scientifically rigorous: All of our models are scientifically backed and undergo rigorous scientific and clinical validation. After the model is coded into DoseMeRx dosing recommendations are simulated in over 5,000 patients. The model is then sent to an independent pharmacometrician who re-runs those 5,000 simulations using an FDA recognized standard tool. The results generated from the two separate methods must be in agreement before the model is available for use. This ensures scientific and clinical validity. 

How does DoseMeRx differ from other solutions operationally?

• Interoperability and improved safety: Unlike free online tools and Excel calculators, DoseMeRx can be integrated into your pharmacy surveillance software such as Sentri7, VigiLan ILÚM Insight® or your hospital’s EHR eliminating the need for data entry and reducing the risk of manual errors. It also permits the sharing of data across your health system for consistent patient care. With DoseMeRx, all the patient information is saved, therefore preventing the need to re-enter data and re-do calculations.

• Allows centralized evaluation of key performance metrics: Pharmacy Administration at the local, regional, or corporate level can quickly obtain and evaluate key clinical and operational metrics. This allows for benchmarking across the system and provides information that can be easily used for documentation for Accreditation organizations such as The Joint Commission.

• Improves efficiency: Requiring manual entry of levels and patient information each time a pharmacist must calculate a dose, results in lost time for the pharmacist to perform other key job functions and creates operational inefficiencies. It takes an estimated 15 minutes for a pharmacist to calculate and analyze dosing recommendations using two-point kinetics.⁴ With DoseMeRx, this calculation can be performed in seconds.  All clinical information is seamlessly available at the point of care and incorporated automatically into clinical notes.

• Technical support and training: DoseMeRx provides 24/7 support year-round for anyone using our paid platform through a convenient online chat function, as well as full range of opportunities for staff training and education. For online tools and calculators, there is no clinical or technical support provided.

• Easy-to-use for all pharmacists at any experience level: The features within DoseMeRx ranked it as the easiest to use software based on an independent study.

How important is data security?

Purchasing clinical decision support software means your IT team will be involved at some stage or another in which tool is permitted for use at your institution.

Healthcare institutions are becoming increasingly vulnerable to security attacks and ransomware. In 2020 alone, the number of US healthcare organizations that experienced a ransomware attack doubled.⁶

DoseMeRx ensures that your patient data is secure. We maintain the highest data security certification, HITRUST. HITRUST CSF certification validates that the DoseMeRx platform meets key regulations and protects sensitive information.⁷

Consider your clinical liability risk

Free Online Tools

Many of the free dosing tools that are currently available online assume no liability for the use of their calculator or software. This requires the user to assume all of the risk for using a product where the clinical validation, scientific integrity, and testing that is conducted to ensure accuracy is virtually unknown.

This leaves the user to carry 100% of the liability when they use the tool. In addition, if there are any known “bugs” or modifications that must be made, then the user must be reliant on the person maintaining the tool or website to make any modifications or corrections. In some cases, the calculator may not even be maintained anymore.

“Homegrown” Excel spreadsheets

Many institutions have developed their own Excel spreadsheets that will perform two-point calculations.

These calculators utilize a cell protection function which “should” protect users of the tool from modifying the calculations or cell functions, but this is not 100% reliable.

The reusable Excel calculators are also prone to file corruption.  Using a self-built tool that is reused by pharmacists to calculate doses can be very high risk since any modifications will result in an error that could be potentially reproduced in hundreds of patients depending on how the tool is used.

Key takeaways

Depending on your requirements, there are lots of options available. Homegrown spreadsheets and first-order kinetics calculators do offer an option to calculate AUC, although there are trade-offs that the user has to make in terms of convenience, workflow, and liability associated with no-cost tools.

However, DoseMeRx offers many clinical, operational, and safety benefits for health systems. DoseMeRx has six different scientifically validated models that can be applied to almost any patient who is receiving vancomycin across the health system.

By utilizing the Bayesian approach offered through DoseMeRx, appropriate dosing of vancomycin can be achieved before the patient is at a steady-state allowing the patient to receive the right drug at the right dose earlier in therapy.

By standardizing to a single vancomycin dosing tool, it will allow institutions and health systems to standardize protocols and care across a wide diversity of hospitals. In addition, key clinical metrics can be followed and reported which helps to support hospital and corporate level operations and can also be used to support Joint Commission Accreditation.

Operationally, making DoseMeRx available at the point of care will save pharmacists time as they will not have to manually enter information. This offers additional safety benefits because it reduces the potential for medication errors to be made since data entry does not have to be manual.

Finally, DoseMeRx offers the highest level of data security through our HITRUST certification, ensuring that all patient data is protected and secure.

References

1. Rybak MJ, Le J, Lodise T, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy 2020; 77 (11), pages 835–864.
2. https://www.idstewardship.com/a-look-into-free-online-vancomycin-dosing-calculators/
3. Vala M, Mercuro N, McCoy C. Vancomycin Therapeutic Drug Monitoring: How to Hit the Curve. Presented at ID Week (Virtual), October 2021.
4. Beccari MV, Seabury RW, Mogle BT, et al. Cost Comparison of AUC:MIC -versus trough-based vancomycin monitoring for MRSA bacteremia. Journal of the American Pharmacists Association 2020; 60 (5): 729-733.
5. Kumar A, et al. An evaluation of the user-friendliness of Bayesian forecasting programs in a clinical setting. British Journal of Clinical Pharmacology 2019; https://doi.org/10.1111/bcp.14066
6. https://www.hipaajournal.com/cost-2020-us-healthcare-ransomware-attacks-21bn/
7. https://staging.doseme-rx.com/news-media/articles/hitrust-certification