Advancements in pharmaceutical formulations often bring a multitude of safety and efficiency benefits to patients and providers. However, these benefits can be accompanied by challenges that require careful consideration before the new drugs are added to a facility’s formulary. Humulin R U-500, for example, is a concentrated human insulin product that may allow indicated individuals to inject up to 80% less volume per injection per day. Available as an insulin pen and vial to be used with product specific insulin pen needles and syringes, respectively, some organizations may be hesitant to have this insulin on formulary because of significant errors reported involving drawing it up from a vial and/or inadvertently using tuberculin or U-100 insulin syringes.1,2

WVU Medicine is a health system spanning West Virginia, Maryland, Ohio, and Pennsylvania that consists of 17 hospitals, including WVU Hospitals (WVUH), the 690-bed flagship hospital of the health system located in Morgantown, West Virginia. Due to the safety concerns highlighted above, U-500 insulin of any kind was designated as nonformulary within the system. Instead, this product required conversion to formulary insulin products.

This formulary omission created complex standardization and safety concerns for patients taking this insulin at home, with downstream effects that impacted both operational pharmacy practices and clinical outcomes. With these concerns in mind, a medication use evaluation was conducted from June 2014 to July 2019 to better evaluate formulary insulin conversion practices involving patients taking the insulin regimen at home. From there, a safety-focused implementation plan was developed to ensure a seamless incorporation of the product to formulary.

Background

From June 2014 to July 2019, there were 35 unique patients on U-500 insulin at home who were hospitalized at WVU Medicine and converted to a formulary insulin product. Of the 35 total patients, there were 29 unique inpatient insulin regimens following conversion to a formulary insulin product. Among those patients, there were 99 events of blood glucose (BG) readings resulting greater than 300 mg/dL and 17 events resulting with a BG less than 70 mg/dL. Thus, the process of adding a U-500 insulin product to health system formulary began in August 2019 to standardize practice and optimize management of these patients.

Data Driven Foundation

When beginning a medication use evaluation, it is important to compile all the data and literature available on the product. A review of clinical primary literature, published safety data, current health system insulin formulary products, outside institution practices, and available U-500 insulin products was completed. Financial data were generated for each insulin product (vial and pen). A formal proposal for the addition of the U-500 KwikPen to the health system formulary was developed to include institutional data details, safety considerations, and financial implications.

Prior to taking the proposal through the formulary addition process, it is necessary to share all the information with a multidisciplinary focus group of key stakeholders for feedback. Pharmacy representatives involved in the insulin pen focus group included internal medicine clinical pharmacists, directors of pharmacy across the WVU Medicine Health System, pharmacy operations, and pharmacy medication safety and compliance divisions. Nonpharmacy representatives included physicians from the endocrinology department as well as representatives from the diabetes education department. Feedback regarding the formulary addition of the insulin pens was discussed with each individual and the proposal was subsequently strengthened to include insight from a broad group of stakeholders. This step was invaluable in ensuring a collaborative, interdisciplinary approach, building buy-in, and working to mediate potential problems during the operational phase of adding this insulin to hospital formulary.

Safety Concerns

The insulin pen proposal was presented at the WVU Medicine enterprise pharmacy & therapeutics (P&T) formulary subcommittee in November 2019, where a unanimous vote approved the addition to hospital formulary. The P&T formulary subcommittee is a subcommittee of the WVU Medicine enterprise P&T committee that consists of both physician and pharmacy representatives across the health system. Following subcommittee approval, the proposal was presented and approved at the WVU Medicine enterprise P&T committee in January 2020.

To accommodate all hospitals within the health system, product restrictions were developed with the help of the department of endocrinology. Given the significant safety concerns with inadvertent prescribing of concentrated U-500 insulin and the continuation of home therapy during hospitalization, it was decided that an endocrine consult would be required for all inpatient use of the product, as available throughout the health system. Specifically at WVUH, restriction criteria were developed that require all new start U-500 insulin orders to include publication of an endocrinology consult note prior to therapy initiation, while the continuation of home therapy simply requires that a consult order be placed at the time of ordering. This restriction was created in an effort to avoid potential delays in care for patients who take this insulin at home and may be admitted during off-hours. The diabetes education department, when available, accepted responsibility to educate bedside nursing staff during weekdays, covering issues such as how to use insulin pens, how to acquire pen needles, and to answer any questions that may arise. Due to concerns for potential confusion of insulin products, there was an intentional focus on including specialists in endocrinology and diabetes education throughout all steps of the process.

Operational Approach

Procurement

With approval of the insulin from the WVU Medicine enterprise P&T committee, the operational phase began in February 2020 with product acquisition. This twofold process requires the purchase of both the insulin pen itself as well as the insulin pen needles. Using the projected patient volume data from the medication use evaluation, U-500 insulin pen par levels were developed, and purchasing availability was confirmed through the pharmacy wholesaler. At WVUH, there are no other insulin pen products on formulary; thus, the need to acquire needles for insulin pen administration was a new practice.

The acquisition of insulin pen needles was a separate task, with several proposals developed and discussed. It was ultimately decided that insulin pen needle procurement and distribution would be under the purview of the hospital’s supply chain department. Subsequently, product specific information involving the preferred needle size and ordering IDs were shared with the supply chain department to support their evaluation of product ordering feasibility. A formal product request was created for the insulin pen needles, which included the expected number of patients, par levels, and an estimated go-live date. After compiling this information, the supply chain department confirmed that they would be able to order and stock the insulin pen needles for hospital use.

EMR Build

With the establishment of insulin pen and insulin pen needle availability, attention turned toward the product build in the hospital’s electronic medical record (EMR). The product EMR build considerations were extensive and required over 10 months to perfect. Issues to address included the creation of the order itself with inclusion of diabetes education and endocrinology consult language, discussion of detailed order instructions, label creation, label routing, operational dispense logic, redispense logic, links to education and guidance documents within the drug order, dual signoff capabilities, and high alert procedures. Additionally, a best practice alert was created that generated an automatic in basket alert to the diabetes education department at the time of any inpatient U-500 insulin order. Given the complexity of the build, multiple pharmacy stakeholders were involved and tasked with providing continuous feedback to ensure that the ordering process not only was intuitive for end users across the interdisciplinary team, but also that the process would encourage safe use of the insulin products throughout WVU Medicine. After all feedback was implemented, the draft order was added to the test environment, which allowed users to trial the ordering capabilities on test patients and provide additional feedback prior to moving the order into the production environment.

Storage and Dispensing

Along with the EMR build, specific attention was paid to product placement, proper storage, and dispensing details for the insulin pens within the adult inpatient pharmacy. Because all concentrated insulin products are classified as high alert medications, the insulin pens are designated as a high alert medication throughout the institution, which impacts the processes surrounding refrigerated storage and product dispensing. Specific details regarding actions required by the inpatient pharmacy upon physical dispensing of the insulin pen include:

1. Placement of tamper evident tape to purposely obscure the product specific bar code while also securing the pen cap. Obscuring the product specific bar code encourages scanning of the patient/order specific EMR label rather than the product bar code and helps avoid accidental use of the insulin pen for multiple patients.
2. The EMR label is placed on the insulin pen barrel without obscuring the drug name or expiration date
3. The expiration data label is placed on the pen barrel rather than the pen cap

In addition, standardized workflow documents were created to describe the standard of practice (SOP) for inpatient use of the insulin pens as well as the safe use of insulin pen needles.

Education Efforts

The education phase is a crucial step in the process of adding the insulin pen to hospital formulary and involves multiple levels of education. The SOP document was created first and delineates step by step instructions with details including how to:

• Order the new insulin pen product
• Reference restriction criteria
• Complete required pharmacist documentation upon order verification
• Locate the product in the inpatient pharmacy
• Accurately label and dispense the product
• Deliver the product to the bedside

The document also includes guidance for nursing with instructions detailing insulin pen administration. This draft document was sent to key stakeholders within the pharmacy department to review and then trial the process.

Nursing specific education was initiated in June 2020. Nursing education and feedback began with a presentation of the above processes at the nursing practice council. This committee includes the manager of nursing research and professional development, clinical nursing managers, and clinical nursing preceptors across the institution. Specific discussions regarding the insulin pen and pen needle dispensing as well as insulin administration via the insulin pen device were discussed. Following discussion with nursing staff, an insulin pen how-to document was created with step-by-step instructions (and supporting pictures) to guide nursing through the administration of insulin via a pen device. This document was distributed throughout the nursing units and attached to the insulin order itself in the EMR for easy access. In addition, a summary of the insulin process was created and sent out via email to all nursing managers and departments for subsequent distribution to their staff.

Education was also undertaken for all pharmacy staff. The insulin SOP document was uploaded to the pharmacy website for staff reference, and it was presented at pharmacy practice council, a monthly meeting of all pharmacists, to review and update the department on the ordering process and specific interventions needed by pharmacists. Pharmacy technician education was also completed, with a specific focus on appropriate labeling, dispensing, and delivery of the product. With all the above education complete, a final focused educational alert was distributed to all pharmacists and nurses across the institution.

Go-Live

With product acquisition, EMR builds, product restrictions, product storage, product dispensing, and education complete, a go-live date was set for January 2021. This date was communicated to all key stakeholders and allowed time for official ordering of the insulin pen and insulin pen needles, as well as time for any last minute feedback. After onsite product availability was confirmed and with assistance from the EMR support, the insulin was officially added to the WVUH formulary and made available for ordering in January 2021.

Post Implementation Analysis

The Plan Do Study Act cycle, a management method used for the continual improvement of processes and products, was utilized to study the implemented change and identify areas for process improvement. Feedback was solicited after the go-live date from physicians, pharmacists, and nursing, and repeat education was provided to nursing specifically regarding the supply of insulin pen needles from the supply chain team. Additional pharmacy education was provided to address specific scenarios that would require redispensing the insulin pen. Overall, the addition of the insulin pen proceeded quite smoothly, with positive feedback from physicians, as well as nursing and pharmacy staff.

In January 2022, approximately 1 year after addition of the insulin to formulary, a repeat medication use evaluation was conducted to assess blood glucose management in U-500 insulin treated patients, as this was the original impetus for adding the medication to formulary. Over an 11-month period from January 25, 2021 to December 31, 2021, 37 patients received the insulin pen during their inpatient stay. The results of this repeat medication use evaluation revealed that the addition of the insulin pen to WVU Medicine - WVUH formulary decreased both hyperglycemic events (BG > 300 mg/dL) and hypoglycemic episodes (BG < 70mg/dL) (see the TABLE).

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Key Points

When reflecting on the impact of this formulary addition, several key steps were imperative to its success (see the FIGURE). Perhaps the most important step in the process was inviting the early involvement of key interdisciplinary stakeholders. Ensuring the engagement of both pharmacy and nonpharmacy representatives from the early stages of development allowed for a collaborative effort inclusive of diverse ideas, brainstorming, thinking outside the box, and consideration of many different viewpoints reflective of the team members’ distinct skill levels. Incorporating feedback from a diverse group of stakeholders allowed the proposal to pass though both local and health system committee approval without issue and saved countless hours of discussions had opinions not been sought out earlier.

Click here to view a larger version of this FIGURE.

Additionally, development of a formal SOP document was crucial to the success of this project. This document outlines every detail of the process including ordering, storing, verifying, labeling, dispensing, and delivery, as well as staff education. With the inclusion of pictures, all pharmacy staff—from technicians to pharmacists to managers—were able to reference it for clarification of their role and responsibilities. Creation of the SOP document made a significant difference in gaining staff buy-in for this change. We strongly recommend adopting this approach for complicated formulary additions.

Conclusion

Evaluating a new medication for formulary can be a daunting task and for those products with the possibility of adverse events, exclusion may be the initial reaction. Nevertheless, there are situations whereby not providing a medication can present additional safety and efficacy concerns. With tremendous support from both pharmacy and physician leadership, as well as a significant amount of time, energy, and thoughtful reflection invested by all parties involved, the review and implementation of new medications and processes can be completed to achieve the ultimate goal of ensuring optimal care for patients. By prioritizing safety and efficiency, and bolstering efforts through detailed SOP and education development, a multidisciplinary process can successfully resolve these daunting issues.

References

1. de la Peña A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care. 2011;34(12):2496-2501.
2. Hood RC, Arakaki RF, Wysham C, et al. Two treatment approaches for human regular U-500 insulin in patients with type 2 diabetes not achieving adequate glycemic control on high-dose U-100 insulin therapy with or without oral agents: a randomized, titration-to-target clinical trial. Endocr Pract. 2015;21(7):782-793. Erratum, 2016;22(7):905.

Abigail Hoff, PharmD, BCPS, CTTS, is a clinical pharmacy specialist in internal medicine at WVU Medicine – WVU Hospitals in Morgantown, West Virginia. She earned her doctor of pharmacy degree at the University of Cincinnati in Cincinnati, Ohio in 2018. Abigail completed a PGY-1 acute care pharmacy residency and a PGY-2 internal medicine pharmacy residency at WVU Medicine in Morgantown, West Virginia in 2019 and 2020 respectively.

Sheena Burwell, PharmD, BCPS, CTTS, is a clinical pharmacy specialist in internal medicine at WVU Medicine – WVU Hospitals in Morgantown, West Virginia. She earned her doctor of pharmacy degree at the University of Findlay in Findlay, Ohio in 2014. Sheena completed a PGY-1 pharmacy practice residency at the University of Toledo Medical Center in Toledo, Ohio, followed by a PGY-2 internal medicine pharmacy residency at University of Missouri Health Care in Columbia, Missouri.