The Case

A fourteen-year-old girl presented to the emergency department with a one-week history of fatigue, polyuria, polyphagia, and polydipsia. Laboratory studies confirmed a new diagnosis of type 1 diabetes mellitus without ketoacidosis, for which the patient was admitted. The patient’s care was managed by a multidisciplinary team consisting of a pediatrician, endocrinologist, dietitian, psychologist, and a social worker. After a three-day hospital stay, the patient was ready to be discharged and the medications intended for home use were delivered to the patient’s bedside.

During the routine medication check prior to the patient’s discharge, the resident physician noticed a discrepancy. An insulin pen and pen needles had been ordered, but an insulin vial and extra insulin syringes were delivered to the patient’s bedside without the provider having been notified of the product switch. Neither the patient nor the parents had received education on how to draw up and administer insulin using a vial and syringe. The pharmacy was contacted for clarification on the discrepancy; staff reported that the insulin pen was out of stock, so the insulin vial was substituted because it contained the same active ingredient. The insulin product switch was declined, and another pharmacy was contacted to provide the insulin pen, which was delivered to the patient’s bedside the following day.

Although the patient’s hospital stay was prolonged by one day, her parents expressed gratitude for the resolution. No harm was done to the patient, but there was potential for harm, if the patient and her family had received a medication that they were not trained to use correctly.

The Commentary

By Hana Camarillo, PharmD, BCACP, CDCES

Background

Insulin-related medication errors are common in hospital settings and can be especially problematic when a patient transitions from one level of care to another.^1,2,3 The Institute for Safe Medication Practices (ISMP) considers insulin to be a high-alert medication due to the potential for significant patient harm when insulin is used incorrectly. Medication errors involving insulin that occur at the point of hospital discharge can lead to patient harm. For a patient with type 1 diabetes mellitus, underdosing insulin can cause severe hyperglycemia, which can lead to diabetic ketoacidosis and hospitalization. On the other hand, overdosing insulin can cause severe hypoglycemia, coma, seizures, and even death.

Drug Interchangeability

The United States Food and Drug Administration (FDA) classifies insulin as a biologic (i.e., a complex molecule that is derived from a natural source).^4,5 ‘Interchangeability’ is a regulatory term that indicates whether a biologic medication and its delivery device – in this patient’s case, a pen prefilled with insulin – can be substituted for the insulin vial containing the same active ingredient without the intervention of the prescribing healthcare provider.⁶ Interchangeability standards are described under section 351(k) of the Biologics License Application. According to the FDA’s Purple Book,⁷ even if an insulin pen and vial contain the same active ingredient, they differ in terms of the delivery method, administration, and sometimes concentration. Due to these differences, patient education is needed to ensure safe and effective use. Insulin vials require the patient (or caregiver) to draw up insulin via a syringe. Inaccurate measurement of insulin via a syringe can result in dosing errors and patient harm.

In the Era of Drug Shortages

Medication substitutions are becoming increasingly common due to supply chain issues. Drug shortages in the United States have reached a 10-year high according to a survey published by the American Society of Health System Pharmacists. As of July 2023, there were 309 active, ongoing drug shortages reported, and 99% of respondents reported experiencing drug shortages. One-third of these shortages were categorized as critically impactful, defined as rationing, delaying, or canceling treatments or procedures.⁸ Pharmacy respondents reported managing drug shortages by changing to therapeutic alternatives (97%), implementing rationing criteria (85%), changing order sets or protocols (75%), delaying or canceling treatments or procedures (42%), and a variety of operational strategies for acquiring and managing drug inventory.

The impact of drug shortages in 2023 is felt by patients, physicians, nurses, pharmacists, pharmacy technicians, and pharmacy purchasing agents, compromising patient care and creating high levels of stress for all parties involved .⁹ This patient’s case highlights a patient safety issue that can arise during transitions of care in the setting of supply chain issues. Changing from an insulin pen to a vial at the point of hospital discharge requires patient (or caregiver) education on how to prepare and administer the dose. Without appropriate education, the patient could be at high risk of insulin dosing errors, which could lead to catastrophic outcomes.

Approach to Improving Safety

Cultivating a culture of communication and collaboration across providers plays a vital role in patient safety by decreasing risk for errors during transitions of care. In this patient’s case, a patient safety event was avoided due to the inpatient discharge medication check performed by the resident physician on duty. In the era of increasing medication substitutions due to ever-present supply chain issues, a more predictable workflow may be needed to prevent discharge delays and patient dissatisfaction. An expedited approval process for therapeutic alternatives (intended for use when the standard process is not timely enough to meet the demand) may be useful, when appropriate. Any decisions about alternative therapies should involve stakeholders from medicine, nursing, pharmacy, and other healthcare team members who may be impacted.¹⁰ In the case of non-interchangeable high-alert medications, it is prudent for the ordering health care provider to be consulted BEFORE any pharmacy substitution so that the patient’s needs can be assessed, and education can be provided in advance of the patient’s discharge. Substitutions involving other medications, which are not high alert, may or may not require advance approval, depending on the complexity and potential impact.

Systems Change Needed

Patient safety is an inherent responsibility of the clinical microsystem. A microsystem refers to a small, functional unit within a healthcare organization in which patient care is delivered.¹¹ This unit can be a specific department, a clinical team, or even a single healthcare process. Improving patient safety within clinical microsystems begins with raising the work unit’s understanding of its role as a microsystem.¹² By focusing on microsystems, healthcare organizations can address patient safety concerns by making targeted improvements, yet organizational leaders must recognize that microsystems interact with each other and optimizing one system alone may not suffice to solve safety problems.¹² This approach recognizes that patient safety is the result of the collective efforts of many individuals, teams, and processes, all working together within their specific microsystems. In this case, the microsystems included the hospital’s resident medical staff, working under the guidance of a pediatric hospitalist and pediatric endocrinologist, and the pharmacy staff who were tasked with filling the discharge prescriptions.

In cases of this type, the medical and nursing staff are often under pressure to discharge patients quickly so that beds can be made available for incoming patients, while the pharmacy staff is under pressure to fill prescriptions quickly. The medical staff worked around the hospital pharmacy’s supply chain problem by sending discharge prescriptions to an outside pharmacy for delivery to the inpatient unit. Most workarounds have limitations, and this approach may not be feasible in all communities. If the medical and nursing staff had known about the supply chain problem one day earlier, then they could have educated the patient and her family about syringe administration of insulin or sent the order earlier to the outside pharmacy, thereby avoiding the cost and inconvenience of an extra day in the hospital. If the hospital had needed this patient’s bed for a sicker patient, they might have directed her family to drive to the outside pharmacy to pick up the insulin pens. Any of these workarounds could have been effective with appropriate and timely communication, but the resident physician’s role in identifying the discrepancy before the patient’s discharge was absolutely critical. From the Safety-II perspective, it would be useful to understand the resilience of the discharge process, and how the health care organization in this case enabled and supported its medical staff do detect the medication substitution before it was too late.

Take Home Points

• Drug shortages in the United States are at a 10-year high, impacting patient care delivery and causing high levels of stress for patients and healthcare teams.
• The U.S. Food and Drug Administration’s Purple Book⁷ can be leveraged as a resource to determine whether a biologic medication can be interchanged with another medication at the pharmacy level without the intervention of the ordering healthcare provider.
• In-person, phone, or electronic communication between the pharmacy and the treating health care provider must occur before substituting a non-interchangeable medication for self-administration at the point of hospital discharge.
• Assessing the patient/caregiver’s ability to administer the medication and using the teach-back method to confirm understanding are essential to medication safety.
• Always perform a last-minute check of the patient’s discharge home medications; this is the last step before the patient leaves the healthcare facility and the last chance to identify errors and resolve any confusion or misunderstandings.

Hana Camarillo, PharmD, BCACP, CDCES
Clinical Pharmacist, Endocrinology
Department of Pharmacy
UC Davis Health
hcamarillo@ucdavis.edu

References

1. Bain A, Silcock J, Kavanagh S, et al. Improving the quality of insulin prescribing for people with diabetes being discharged from hospital. BMJ Open Qual. 2019;8(3):e000655. [Free full text]
2. Bain A, Nettleship L, Kavanagh S, et al. Evaluating insulin information provided on discharge summaries in a secondary care hospital in the United Kingdom. J Pharm Policy Pract. 2017;10:25. [Free full text]
3. Breuker C, Macioce V, Mura T, et al. Medication errors at hospital admission and discharge in type 1 and 2 diabetes. Diabet Med. 2017;34:1742–6. [Available at]
4. What Are "Biologics" Questions and Answers. U.S. Food and Drug Administration. Accessed September 14, 2023. [Available at]
5. Insulin is now a biologic—what does that mean? American Diabetes Association. Accessed September 14, 2023. [Available at]
6. Franklin J. Biosimilar and interchangeable products: the U.S. FDA perspective. ACCR 2018. Accessed September 14, 2023. [Available at]
7. The Purple Book: database of licensed biological products. U.S. Food and Drug Administration. Accessed September 14, 2023. [Available at]
8. Severity and Impact of Current Drug Shortages: June/July 2023. American Society of Health System Pharmacists. Accessed September 14, 2023. [Available at]
9. Adams K. Drug Shortages Not Only Exacerbate Healthcare Burnout But Can Also Harm Patient Care. MedCity News, 8/15/2023. Accessed September 14, 2023. [Available at]
10. Weathering the storm: managing the drug shortage crisis. ISMP Medication Safety Alert! 2010;15(20):1-4. [Free full text]
11. Ambulatory Care Improvement Guide, Section 4: Ways To Approach the Quality Improvement Process. Agency for Healthcare Quality and Research. Accessed September 14, 2023. [Available at]
12. Clinical Microsystem Action Guide: Improving Health Care by Improving your Microsystem. Version 2.1 (2004). Accessed September 14, 2023. [Available at]