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Enhancing the Patient and Nurse Experience in Large-Volume Subcutaneous Drug Delivery: The Shift to Comfort

From ONdrugDelivery September 2024:

Biologic drugs, such as monoclonal antibodies (mAbs), are a class of medications that represent a rapidly expanding category of treatments. They treat serious diseases, including cancer, metabolic disorders, cardiovascular conditions, genetic disorders, and immunological diseases. These drugs were initially designed for intravenous (IV) administration due to their large, complex molecular structures, which are poorly absorbed when taken orally. However, because IV administration can sometimes be painful, less tolerated by patients, and resource-intensive, these factors have driven the growth of subcutaneous (SC) delivery options.

With the rising popularity of biologic drugs in the past decade, their administration has gradually shifted from IV to SC delivery. The SC delivery method has since been adopted in oncology as an alternative to traditional IV infusions, too. For instance, Roche launched SC formulations for rituximab, pertuzumab, and trastuzumab, which were initially approved for IV administration. Clinical studies have demonstrated the long-term efficacy and safety of these SC formulations, confirming them as valid therapeutic alternatives.

The shift from IV to SC administration of biologic drugs has been facilitated by advances in high-concentration formulation development, devices for injecting large-volume doses (e.g., on-body delivery devices), and permeation enhancers. While not essential for large-volume SC delivery, permeation enhancers such as hyaluronidase, have been at the forefront of this transition.

One of the major challenges with administering large-volume subcutaneous (SC) drugs combined with permeation enhancers is the administration experience for nurses. Currently, these drugs are given through a labor-intensive manual injection process using a needle and syringe. This method requires the nurse to exert pressure, sometimes taking several minutes to complete. During this time, the nurse must closely conduct and monitor the procedure to ensure the medication is delivered safely and accurately. Despite the considerable time and effort required to administer these drugs, such as daratumumab/hyaluronidase, rituximab/hyaluronidase, or pertuzumab/trastuzumab/hyaluronidase, the preferences and challenges faced by nurses are often overlooked and underappreciated.

While the syringe format enables faster drug administration compared to IV infusions, it comes with several drawbacks. These include repetitive strain and needlestick injuries for nurses, as well as an increase in patient discomfort due to the use of larger gauge needles. The syringe method can potentially lead to repetitive strain injuries in nurses, who must apply consistent pressure for extended periods when administering large-volume formulations to multiple patients each day. Such injuries often require extended recovery periods, especially for older nurses. Additionally, repetitive strain may hinder the ability of nurses to provide continuous infusions, potentially resulting in drug misuse and escalating both direct and indirect costs.1

A recent meta-analysis involving 42 studies and over 36,000 nurses found that the annual prevalence of work-related repetitive strain injuries among nurses is 77.2%. The most common areas affected are the lower back (59.5%), neck (53.0%), and shoulders (46.8%).2 These injuries might significantly impact mental health, overall quality of life, and contribute to chronic conditions. They could also lead to substantial treatment costs, work restrictions, absenteeism, and high turnover rates among nurses, ultimately affecting patient safety and care quality.3-5 Nurses experiencing chronic repetitive strain injuries might require long-term medication, frequent use of pain relievers, and seek various medical consultations and alternative treatments. The financial burden of these injuries is considerable, with costs for diagnostic tests, healthcare, and worker compensation estimated between $50,000 and $100,000 per nurse.5,6

The impact of administering large-volume subcutaneous drugs co-formulated with permeation enhancer via syringes extends beyond the difficulties encountered by nurses. Although often overlooked, these drugs generally require larger gauge needles to enhance flow rates and manage the higher viscosity of the co-formulations. It is important to note that while larger gauge needles can improve delivery speed, they also compromise the patient experience because larger gauge needles have larger diameters and are sometimes associated with increased pain and bleeding.7-9 Larger gauge needles can also be more intimidating, potentially increasing patient anxiety, which may require nurses to spend more time counseling patients and can result in missed or delayed injection appointments.10-12

In some healthcare centers, there have been attempts to alleviate the manual administration process by utilizing syringe pumps. However, this approach comes with its own set of challenges: it significantly increases costs, adds complexity to infusion suite arrangement, requires a time-consuming set-up, and often results in crowding and logistical difficulties, further underscoring the need for more efficient and cost-effective alternatives.1

Unlike the syringe format and syringe pumps currently used for administering large-volume SC formulations, on-body delivery systems (OBDS) offer several advantages. OBDSs utilize thinner needles, do not require co-formulation with permeation enhancers, feature a concealed needle mechanism, and most importantly they deliver the drug via the push of a button. These features address many challenges associated with large-volume SC delivery via manual syringes and syringe pumps. The hidden needle design may help alleviate patient needle phobia, while the smaller needles can enhance adherence and minimize pain.12 Given the hands-free delivery feature of OBDSs, they have the potential to reduce the physical strain on nurses, thereby decreasing the risk of repetitive strain injuries. By using an OBDS, nurses wouldn’t have to spend several minutes directly administering drug, allowing them to tend to other patients or responsibilities, potentially improving clinic efficiency by increasing throughput.

In a recent double-blinded online survey conducted by a third-party vendor, nurses with experience administering large-volume SC drugs co-formulated with permeation enhancers (e.g., daratumumab/hyaluronidase, rituximab/hyaluronidase, and pertuzumab/trastuzumab/hyaluronidase) using SC syringes were asked about their experiences and preferences in comparison to the enFuse – an OBDS featuring the first-ever hands-free wearable technology designed to deliver large volumes (5 – 25 mL) of drugs subcutaneously.13

In a detailed scenario that assessed factors beyond just delivery time—including administration method, nurse effort, needle size, time, patient mobility, preparation, and additional direct costs—while assuming the same efficacy, safety, and cost, 44 out of 45 nurses (97.78%) preferred the enFuse over the syringe typically used for administering daratumumab/hyaluronidase. The main reasons for this preference were: 1) reduced nurse effort due to hands-free delivery, 2) less patient pain from a smaller needle, 3) elimination of needlestick injuries with a hidden needle mechanism, and 4) improved clinic efficiency from hands-free operation. 13

Regarding their views on the current needles used for large-volume SC drugs administered via syringes, a total of 94.44% (17/18) of hematology and oncology nurses and 90.91% (20/22) of nurses with experience administering daratumumab/hyaluronidase believed that smaller gauge needles would reduce needle phobia for oncology patients. Additionally, 93.33% of the nurses in the full sample believed that a hidden needle mechanism would eliminate the risk of needlestick injuries.13

When comparing preferences between traditional syringe pumps and the enFuse, an overwhelming 97.78% of nurses in the full sample expressed a clear preference for enFuse for preparation and administration of 5-25 mL of drug product. This finding is particularly noteworthy because, although some centers are investing in syringe pumps to alleviate the physical strain on nurses administering daratumumab/hyaluronidase, the results indicate that nurses would favor an OBDS over a syringe pump. 13

These results and clinical practice trends reveal that speed of delivery is not the foremost consideration for nurses when it comes to large-volume SC administration. Instead, factors such as nurse effort, preparation, patient mobility, needle size, and risk of needlestick injuries play a more significant role in their preferences. While traditional focus on rapid delivery of large-volume SC drugs has often led to compromises in patient comfort and increased physical strain on nurses, the preference for hands-free OBDSs suggests that a shift towards prioritizing overall experience is warranted. Hands-free administration with OBDSs not only reduces the burden on healthcare providers but also enhances their ability to engage in other clinical activities, potentially offering greater economic value despite a longer injection time.

The focus on speed has led to a reliance on larger gauge needles and uncomfortable SC administration practices, inadvertently compromising the overall patient and healthcare provider experience. The overemphasis on quick administration, without considering the discomfort it brings, highlights the necessity for a paradigm shift towards prioritizing patient and healthcare provider experience in large-volume SC drug delivery. As we look ahead to the future of SC drug development, it’s essential to reevaluate the impact of current large-volume SC administration practices to ensure a more patient and provider friendly approach.

  1. Ammor W, Chapron P, Goubil A, Fronteau C, Peyrilles E, Cormier N, “Optimization of the subcutaneous administration of daratumumab”. Poster presented at: European Association of Hospital Pharmacists 26th Congress; 23-25 March 2022 2022; Vienna, Austria.
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  8. Jaber A, Bozzato GB, Vedrine L, Prais WA, Berube J, Laurent PE, “A novel needle for subcutaneous injection of interferon beta-1a: Effect on pain in volunteers and satisfaction in patients with multiple sclerosis”. BMC Neurol. 2008;8(1):38.
  9. Wågø KJ, Skarsvåg TI, Lundbom JS, et al, “The importance of needle gauge for pain during injection of lidocaine”. J Plast Surg Hand Surg. 2016;50(2):115-118.
  10. Usach I, Martinez R, Festini T, Peris J-E, “Subcutaneous injection of drugs: Literature review of factors influencing pain sensation at the injection site”. Adv Ther. 2019;36(11):2986-2996.
  11. Gely C, Marín L, Gordillo J, et al, “Impact of pain associated with the subcutaneous administration of adalimumab”. Gastroenterol Hepatol. 2020;43(1):9-13.
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  13. Desai M et al, “Evaluating Nurse Preferences: A Novel On-Body Delivery System vs. High-Resistance Manual Syringes for Large-Volume Subcutaneous Drug Administration”. Oncology Nursing Society Congress, 24 Apr. 2024