The escalation of cancer drug expenditures, which have surpassed $185 billion globally—with the United States accounting for $75 billion—calls for strategies to mitigate costs and reduce drug waste.1 A significant contributor to this waste is the dosing of cancer medications based on patient specific metrics, such as body weight or body surface area, leading to the frequent disposal of leftover drugs from single-dose vials (SDVs). To address this issue, the Mayo Clinic Cancer Center implemented targeted interventions aimed at reducing drug waste while also tracking and capturing the total amount of drug wasted.

The Mayo Clinic Cancer Center’s approach demonstrates an iterative model of medication stewardship—one that combines advanced EHR capabilities, interdisciplinary collaboration, stakeholder engagement, and data driven decision-making to propel continuous improvement in drug utilization efficiency and waste reduction. This strategy focuses on dose rounding, precise drug waste tracking, and targeted interventions to optimize medication use and cost efficiency. Developed over several years, these cumulative waste reduction initiatives leverage advanced integration tools within the EHR to streamline workflows, automate reporting, and align processes with established guidelines.

Dose Rounding Development

Initial efforts began with developing and integrating an automated dose rounding system into the EHR at Mayo Clinic. This system adjusted calculated doses to the nearest vial size within a 10% variance, thereby minimizing the use of partial vials and reducing waste. The objective of the dose rounding policy was to minimize drug waste and enhance operational efficiency by standardizing dosing practices across the institution.

Stakeholder engagement played a critical role in the program’s development, with key representatives from outpatient infusion centers, inpatient facilities, and research units actively contributing to the planning and execution phases. An interdisciplinary team—pharmacists, informatics specialists, clinical leaders, and operational staff—collaborated to design, implement, and refine strategies, ensuring alignment across departments and care settings. The team prioritized transparent communication and accountability at all levels, establishing clear roles for the stakeholders responsible for reviewing, investigating, and resolving drug waste events.

Customized reporting tools were developed to provide detailed analytics, enabling the team to monitor the financial and operational impact of dose rounding strategies and drug waste management practices. These reports facilitate real-time visibility into utilization trends, cost savings, and areas requiring intervention. Data driven insights allow for ongoing feedback loops, enabling stakeholders to make evidence based adjustments to rounding protocols and waste reduction measures. Training and education sessions, led by medication safety officers and clinical informatics teams, ensure consistent adoption of best practices and reinforce compliance with safety protocols.

Implementing Dose Rounding Rules

The dose rounding policy is founded on two primary principles. First, doses are rounded to the nearest commercially available vial size if the adjustment remains within a 10% variance from the originally calculated dose. This threshold is based on the Hematology/Oncology Pharmacy Association’s (HOPA) position statement, ensuring clinical appropriateness and safety.2 Second, when vial size-based rounding is not feasible, doses are adjusted to the nearest measurable and clinically appropriate amount.

Developing these rounding guidelines was a collaborative effort led by a multidisciplinary working group including oncology pharmacists, pharmacy technicians, pharmacy leaders, and an informatics pharmacist. Each member brought expertise from different operational areas, including outpatient infusion centers, inpatient care units, and research facilities. A diverse representation of expertise ensures the policy is comprehensive and adaptable to varying clinical settings.

To guarantee the appropriateness of rounding for each medication, the working group conducted an extensive review of individual drug characteristics, including dosing guidelines, available concentrations, and vial sizes. Each drug underwent a rigorous assessment to determine specific rounding parameters. Prior to implementation, the policy underwent multiple levels of institutional review and approval, including endorsement by the pharmacy and therapeutics committee. Upon approval, the dose rounding protocol was integrated into the institution’s medication management system, initially encompassing over 90 oncology medications, including biologic and oncolytic agents. A dynamic approach was adopted to ensure the policy remained current; as new cancer drugs receive approval for clinical use, they are systematically evaluated, and rounding guidelines are established before being added to the protocol.

The standardized dosing approach incorporates two key strategies:

• Dose rounding
• Dose banding

Both strategies aim to optimize drug utilization while minimizing waste. Dose rounding adjusts calculated doses to remain within ±10% of the original dose, in alignment with established clinical guidelines. Dose banding, on the other hand, standardizes doses into predefined ranges or “bands” to address scenarios where drug concentrations and vial sizes do not align evenly. For example, trastuzumab, with a concentration of 21 mg/mL, was available in vials containing 150 mg (approximately 7.14 mL per vial) at the time of implementation. This vial size did not align neatly with the 10% dose rounding threshold, creating a challenge in optimizing waste reduction. To address this, dose bands were introduced, allowing doses to be rounded to the nearest measurable increment of 21 mg (1 mL) or directly to the vial size when clinically appropriate.

Before deployment, the pharmacy informatics team rigorously tested these rounding and banding protocols in a controlled proof of concept environment within the EHR. This testing phase ensured accuracy, consistency, and alignment with patient safety standards. Following successful validation, the automated dose rounding and banding rules were formally integrated into the EHR in March 2018, marking a significant step forward in improving efficiency and reducing drug waste in oncology care.

Dose Rounding Results

To assess the impact of dose rounding, we compared the originally prescribed doses with the adjusted, rounded doses. Drugs were categorized as oncolytic if they included traditional chemotherapy agents, monoclonal antibody drug conjugates, or biologic therapies with similar mechanisms of action. The analysis focused on three key measures:

1. Cost Savings: When a dose is rounded down, and no additional SDV is required to meet the new dose, the cost of the unused vial is considered a cost saving.
2. Waste Avoided: If a dose is rounded up to align with the nearest vial size, the difference in cost between the original dose and the rounded dose is calculated using the Centers for Medicare & Medicaid Services billable unit price. This difference represents the cost of waste that was successfully avoided through rounding.
3. Drug Waste: If a dose can not be adjusted within the 10% rounding threshold and require partial use of an SDV, the remaining drug is classified as waste. This waste was manually documented in the EHR during preparation.

Analyzing these measures over 3 years provided a comprehensive view of the financial and operational impact of dose rounding and highlighted areas where additional efficiencies might be achieved (see the FIGURE). Results revealed that 36.1% of doses were rounded down, generating $39.75 million in cost savings, while 35.8% were rounded up, avoiding $9.95 million in waste. However, 28.1% of doses could not be rounded, resulting in $25 million in waste. Despite significant savings, the findings highlight the need for additional strategies, including policy changes and vial optimization, to address the remaining inefficiencies.

While the automated dose rounding initiative demonstrates meaningful progress in reducing drug waste and generating significant cost savings, it is only the first step in addressing the broader challenges associated with oncology drug utilization. True optimization demands more comprehensive solutions—not only to further minimize drug waste but also to establish robust systems for tracking, reporting, and analyzing waste patterns. There are substantial opportunities for additional enhancements based on the demonstrated potential of systematic strategies within EHRs.

Comprehensive Waste Optimization

The next step for the waste reduction program was to look beyond minimizing waste and establish robust systems for tracking, reporting, and analyzing waste patterns. Historically intransigent, drug waste often stems from the misalignment between SDV sizes and the individualized dosing requirements for oncology patients. While SDVs help ensure sterility and reduce contamination risk, the fixed dose vial sizes lead to frequent disposal of unused medication.

Efforts by organizations such as the U.S. FDA to encourage manufacturers to optimize vial sizes have yet to produce widespread changes. Exacerbating this challenge is a lack of clear guidance on drug waste management and disposal, leaving cancer centers to navigate this issue on an individual basis.

With the ultimate goal of reducing denials and claim adjudication, The Mayo Clinic Cancer Center created a system to redefine how drug waste is captured and reported.

The system serves to:

• Identify drugs expected to have drug waste
• Confirm that the correct amount of waste is documented
• Ensure that drug waste is minimized by using the smallest vial size combinations

Identifying Drugs with Waste

The process of identifying oncology drugs expected to have documented drug waste began by partnering with the IT team to design and build a customized report within the EHR to track SDV medications used in oncology. The report pulled key data points, including the dose ordered, the dose administered, and the expected amount of waste for each SDV. These parameters allowed for a clear and precise assessment of drug utilization and waste documentation, ensuring transparency and accuracy in the process.

A pivotal feature in the report is the “expected amount of waste” column. This column provides a calculated estimate of waste based on the prescribed dose and vial size, offering a benchmark for verification. By leveraging this information, users can cross-reference the dispense module within the EHR to determine whether waste was documented and if the recorded amount matches the expected value. This comparison serves as a vital tool in identifying discrepancies, highlighting any instances where waste might not have been recorded, or where the documented waste amount was inaccurate.

Validating Recorded Waste

The next step involved operationalizing the customized EHR reports to ensure daily oversight of drug waste documentation. This phase leveraged the expertise of pharmacists to ensure the accurate capture of drug waste and maintain the program’s integrity.

Designated pharmacists generate a daily drug waste report from the EHR, which includes all SDV medications administered the previous day. The report is reviewed line by line, focusing on the “expected amount of waste” column. For each drug, the pharmacist compares the expected waste with the actual documentation in the dispense module. If discrepancies are identified—such as missing waste documentation or deviations from the expected amount—the pharmacist flags the item for an in-depth review.

The review process is thorough and collaborative, involving an analysis of the compounding process and discussions with key personnel. The pharmacist consults the verifying pharmacist and the compounding technician to understand the root cause of the discrepancy. This could involve reviewing the preparation process, assessing vial sizes used, and ensuring that proper procedures were followed. If the review determines that drug waste has been missed or documented inaccurately, the pharmacist makes the adjustment within the EHR dispense module. In addition to correcting the waste documentation, this adjustment also triggers a notification to the billing and coding teams prompting any necessary billing adjustments, thus meeting compliance and financial accuracy standards.

Optimizing Vial Combinations

The last phase of the program centered on minimizing waste through optimized vial combinations. Recognizing the high cost and value of oncology medications, this phase aimed to reduce waste at the preparation stage by ensuring that the lowest possible combination of drug vials is used to meet the prescribed doses.

To achieve this, we developed a tool allowing technicians to enter the drug name and the required dose for a patient. The tool calculates and displays the optimal combination of SDVs needed to prepare the dose, minimizing the amount of leftover medication. For example, if a dose of 145 mg was required, and the available vial sizes were 100 mg and 50 mg, the tool would recommend using one 100 mg vial and one 50 mg vial, avoiding any scenarios where an additional vial was partially used unnecessarily.

The tool uses a comprehensive database of all SDVs, incorporating information about available vial sizes, stability, and usage guidelines based on the information available online from our wholesaler. This database allows real-time calculations and ensures that every recommended vial combination adheres to the manufacturer’s guidelines and clinical best practices. The system’s design facilitates accurate vial selection and standardizes the process across all technicians, reducing variability and the potential for errors.

Conclusion

By demonstrating the effectiveness of integrating dose rounding protocols, precise waste tracking, and vial optimization tools within the EHR, Mayo Clinic Cancer Center’s drug waste reduction program serves as a model for improving medication stewardship. The program delivers significant cost savings, minimizes waste, and improves operational efficiency by reducing partial vial use and standardizing processes. Building on this foundation, future efforts will focus on vial sharing protocols, multidose vial utilization, and enhanced analytics to further optimize drug use. Ultimately, collaboration among healthcare providers, manufacturers, and policymakers will be crucial for systemic changes that align vial sizes with dosing needs.

References

1. Office of the Actuary. Centers for Medicare & Medicaid Services. https://www.cms.gov/data-research/statistics-trends-and-reports/national-health-expenditure-data/projected.
2. Fahrenbruch R, Kintzel P, Bott AM, et al: Dose rounding of biologic and cytotoxic anticancer agents: A position statement of the Hematology/Oncology Pharmacy Association. JCO Oncol Pract. 14:e130-e136, 2018

Clayton C. Irvine, PharmD, MBA, MS, is the senior manager of oncology cancer care pharmacy at Mayo Clinic. Clayton received his PharmD from West Virginia University School of Pharmacy, an MBA from West Virginia University College of Business and Economics, and an MS in health system pharmacy administration from University of Wisconsin School of Pharmacy.