Evaluating unmet needs in large-volume subcutaneous drug delivery: U.S. payer perspectives on a novel, large-volume on-body delivery system

Abstract

Objective

Existing healthcare systems face finite resource allocation and budgetary constraints, resulting in a substantial need for innovative solutions to enhance service delivery at reduced costs. A novel, user-friendly on-body delivery system (OBDS) was developed which enables administration of large-volume subcutaneous (SC) drugs in both clinical and home-based settings (at-home healthcare professional [HCP] administration or at-home self-administration).

Methods

This research sought to evaluate the potential economic impact of at-home self- or HCP- administration with the OBDS through a comprehensive review of published literature and semi-structured interviews with 17 US payers representing approximately 227 million covered lives.

Results

Published literature on OBDS remains limited, but available research highlights the cost-savings of SC administration due to reduced healthcare resource utilization, particularly with home-based care, and improved patient compliance. In interviews, payers identified several attributes that would help address unmet clinical and economic needs. Clinically, the hidden needle and ease-of-use compared to SC syringe pumps was deemed valuable to improve patient compliance and, as OBDS required minimal training, reduce the risk of administration errors. The flexibility to administer drugs at home (self-administration or HCP-administration) or in-clinic was identified as the most impactful attribute on coverage decision making as it has the greatest potential to reduce costs associated with HCP administration for several therapeutic areas.

Conclusions

Given the ability to help address critical unmet needs for the patient and healthcare system, a large proportion of the payers stated that the novel OBDS would warrant a price premium versus the cost of the standalone SC vial and certainly over the IV counterpart. Future research to quantify the value that OBDS efficiencies could bring to healthcare delivery are warranted.

Keywords:

• Subcutaneous
• on-body delivery system
• wearable injector
• syringe pump
• site of care
• payer
• formulary decision

Introduction

Intravenous (IV) and subcutaneous (SC) biologic drug administration have distinct pharmacokinetic profiles with implications for efficacy, safety, and patient management^1,2. Intravenous administration directly delivers medications to the systemic circulation, offering more rapid onset of action; however, it necessitates the supervision of a trained healthcare professional (HCP). In contrast, SC administration injects medications into the hypodermis, which is less vascularized and results in slower systemic absorption via capillaries. The clinical advantages of SC administration are plentiful and include improved safety through controlled dosing and sustained release profiles, enhanced patient compliance, and less burden on the healthcare system^3–9. Subcutaneous administration offers flexibility and cost-savings and potential for a shift from inpatient procedures to at-home self-administration or at-home HCP administration⁴. Current estimates suggest that up to $265 billion worth of care services in the United States (US) for Medicare fee-for-service and Medicare Advantage patients could shift from traditional facilities to the home by 2025 without a reduction in quality or access^10,11. In addition to lessening the healthcare burden associated with delivery (Figure 1), administering SC medications in home-based settings may offer added convenience and comfort for patients by allowing them to receive treatment in familiar surroundings, which could boost adherence^12,13.

Figure 1. Differences in cost of care by site of treatment.

Abbreviations: ASC = ambulatory surgery centres; HCPs = healthcare professionals; HOPD = hospital outpatient department.

Development of SC drugs has surged, particularly in the areas of oncology and immunology^14–16; however, numerous challenges exist, particularly with large-volume SC delivery. Subcutaneous formulations often necessitate larger volumes (>3 mL), owing to their potentially lower bioavailability and pursuit of a fixed-dose regimen, consequently necessitating higher drug dosages to attain similar exposure^17–19. This factor, coupled with the limited volume capacity of traditional SC devices like autoinjectors, poses difficulties when converting IV drugs to a SC delivery format and often leads manufacturers to consider shorter dosing intervals (i.e. more frequent medication administration) to ensure adequate dose delivery. Although not necessary, large-volume SC drugs can be co-formulated with hyaluronidase to improve absorption. These hyaluronidase co-formulated medications can present challenges for both HCP- and self-administration as they are introduced in a high-resistance, manual-push syringe that can be difficult to use without adequate training and injection technique²⁰. To self-administer the existing large-volume SC biologics that incorporate hyaluronidase, a patient would need to use a SC syringe pump, which introduces additional costs, time, and complexity²¹. Furthermore, drugs co-formulated with hyaluronidase often require the employment of larger needles, which can lead to increased pain, reduced compliance, and irritation at the injection site^22–24.

The route of SC drug administration has evolved over time with the development of prefilled syringes, autoinjectors, SC syringe pumps, and, most recently, on-body delivery systems (OBDS). OBDS are wearable, user-friendly devices designed to deliver large-volume SC doses with several advantages over traditional large-volume SC administration options, including an extended dosing interval due to larger volume capacity, flexibility in the site of care, hands-free mobility during treatment, ease-of-use, and thinner, hidden needles which may improve treatment adherence^21,25. Another benefit of large-volume capacity with an OBDS is the potential reduction in the number of injections required to administer the full treatment dose compared to conventional SC devices. With its greater volume capacity, an OBDS can deliver a large dose through a single injection using a small needle—a feat that would necessitate several injections using a larger needle if performed with conventional SC devices. While this could result in a longer administration duration, it also offers the opportunity for an extended dosing interval and fewer total injections. This is exemplified through evolocumab, which can be administered monthly using one 3.5 mL OBDS with a 29-gauge needle. Alternatively, patients can achieve this monthly regimen using three individual 1 mL autoinjectors or pre-filled syringes, each with a 27-gauge needle intended for consecutive administration within a 30-minute window. However, certain OBDS platforms still face volume limitations which may necessitate the concurrent use of multiple devices to deliver the requisite drug dose. One such example is subcutaneous ravulizumab, which requires weekly administration with two OBDS, in comparison with its IV modality which is administered once every 8 weeks²⁶.

In response to the volume capacity challenge, Enable Injections Inc. developed enFuse® (“novel OBDS”), an OBDS capable of delivering large-volume therapeutics through SC administration. Through an elastomeric delivery mechanism coupled with a hidden needle system, the novel OBDS delivers large volumes subcutaneously at a constant pressure and accommodates a wide range of drug viscosities and volume (5-25 mL per device; Figure 2). On September 28^th, 2023, the novel OBDS was approved by the US Food and Drug Administration (FDA) for use with pegcetocoplan as an alternative option to utilizing a SC syringe pump²⁷. Compared to a SC syringe pump, the novel OBDS offers a more discreet and lightweight design, shorter infusion preparation time, enhanced ease-of-use, greater mobility during infusion, and utilizes a thinner, hidden needle²¹. In a recent study of patients who received SC immunoglobulin (SCIg) to treat primary immunodeficiency, all respondent patients indicated that they preferred the novel OBDS over a SC syringe pump as it simplified drug administration and may help to address challenges associated with self-injection including process complexity, needle phobia, pain concerns, and incorrect administration^21,28. Despite these reported benefits, limited literature explores OBDS value from the perspective of various stakeholders. A literature review and primary research with US payers were conducted to understand whether the novel OBDS device could address the clinical, economic, and humanistic limitations of existing large-volume SC drug administration routes and how this could contribute direct or indirect value to payers, physicians, and patients.

Figure 2. Image of the novel on-body delivery device. A) Unbranded Product X demonstration device in packaging. B) Unbranded Product X demonstration device outside packaging. C) 20 mL vial of deionized water was utilized instead of a therapeutic. After taking off the purple cap, the vial is pushed into the circular transfer base to load the device with deionized water. D) Placement of the unbranded Product X demonstration device dispensing water into a plastic cup.

Methodology

Literature review

A comprehensive, non-systematic literature review was conducted to assess the value of SC drug administration using OBDS from the perspective of payers, with key outcomes of interest including the impact of SC OBDS on direct healthcare resource utilization (HCRU) and costs, indirect costs, and patient experience, compared to IV or traditional SC. Relevant studies were identified using the MEDLINE PubMed database between 2018 and 2023 (inclusive) with English-language restrictions applied. The search strategy included terms to describe OBDS and/or SC drug administration (e.g. “on-body device”, “wearable device”, “wearable injector”, “on-body injector”, “wearable delivery system”, “on-body delivery system”, “subcutaneous”, “SC”) as well as terms to describe value from the perspective of payers (e.g. “payer”, “payor”, “decision maker”, “stakeholder”, “value”, “cost”, “burden”, “resource”, “healthcare resource utilization”, “HCRU”). Reference lists of articles were scanned to capture relevant literature. Articles published prior to 2018 that were considered by the authors to be particularly relevant were also included. Where literature comparing on-body devices to IV or traditional SC was limited, the search was expanded to include studies comparing clinical, economic, and humanistic outcomes associated with SC drug administration versus IV drug administration and stratified by site of care (e.g. home-based sites of care versus inpatient versus outpatient). One researcher screened titles and abstracts of identified citations, followed by full text review of potentially relevant articles to meet eligibility criteria. A second researcher was consulted in cases of uncertainty. The literature review was conducted in accordance with PRISMA guidance.

Payer preference primary market research

Semi-structured blinded interviews with 17 US payers were conducted virtually using videoconference software in January 2023. A semi-structured interview protocol was developed to elicit payer responses via broad, open-ended questions. These questions focused on the perceived value of the novel OBDS's product attributes, coverage decisions, anticipated costs, and reimbursement and distribution matters.

Pharmacy Directors and Medical Directors for regional and national health insurance organizations or healthcare payer organizations responsible for pharmaceutical purchasing in the US were recruited via email using a proprietary stakeholder list. Potential participants were screened to ensure they had at least two years of experience in their current role and were involved in evaluating drug-device combinations for coverage/access decisions under the pharmacy and/or medical benefit. All participants were an active or voting member of their organization’s Pharmacy and Therapeutics Committee and/or Medical Technology Committee.

All interviews were anonymized to protect the identity of respondents and the novel technology was presented to participants as “Product X”. The interviews were conducted by an independent third-party, with no involvement from Enable Injection employees. Prior to the interview, an unbranded sample device of Product X was shipped to participants to permit a demonstration during the interview. Payers were shown a stimuli deck and a short video demonstration of the device use. The 45-minute interviews were recorded and transcribed and were conducted in a voluntary and informed manner by participants. Responses were summarized and categorized by themes, and averages, percentages, and counts were reported for questions that asked participants to provide rankings.

Results

Literature review – route of administration and site of care

Of the 1,294 unique records identified through the PubMed search, 890 were excluded during title and abstract review based on eligibility criteria. The remaining articles were assessed at the full-text level, with 42 relevant articles included. From the 42 relevant articles, 13 focused exclusively on healthcare resource utilization (HCRU), 7 reported on HCRU and indirect costs, 20 focused on patient experience. Two studies reported on both HCRU and patient experience (Table 1).

Table 1. Summary of relevant articles, by theme.

Administrative Method
Comparison	Quantity	References
Health-care resource utilization
IV vs. SC	18	Alsina 2022, Anderson 2019, Bittner 2018, De Cock 2016a, De Cock 2016b, Epstein 2021, Harvey 2022, Igarashi 2014, Kim 2021, Mallick 2018, McCloskey 2023, Olofsson 2016, Parra 2023, Perraudin 2020, Polinsky 2017, Ritchie 2022, Slavcev 2021, Wardley 2021
SC vs. OBDS	0
IV vs. OBDS	0
Other (non-comparative)	4	Bestsennyy 2022, Howard 2019, Schmier 2017, Townley 2018
Indirect costs
IV vs. SC	7	De Cock 2016b, Epstein 2021, Harvey 2022, Igarashi 2014, Olofsson 2016, Parra 2023, Slavcev 2021
SC vs. OBDS	0	None
IV vs. OBDS	0	None
Other (non-comparative)	0	None
Patient experience
IV vs. SC	16	Bell 2021, Bittner 2023, Dashiell-Aje 2018, Denys 2020, Gelhorn 2019, Gonzalez 2022, Mateos 2022, Mateos 2020, McCloskey 2023, Merz 2015, Moreau 2011, Mu 2018, O’Shaughnessy 2021, Overton 2021, Parra 2023, Yenerel 2023
SC vs. OBDS	1	Wasserman 2022
IV vs. OBDS	0
Other (non-comparative)	5	Alsbrooks 2022, Deeb 2022, Joshi 2017, Mahler 2017, Van den Bemt 2019

Healthcare resource utilization and costs

The literature review identified 18 comparative studies assessing HCRU in IV and SC administration methods, and four non-comparative studies^{1–4,10–12,29–44}. Systematic reviews, time-and-motion studies, and economic models on monoclonal antibody therapies consistently showed that transitioning patients from IV to SC was associated with substantial cost savings over the course of treatment due to reductions in HCRU, time for drug preparation, administration, and monitoring (for details, see Table 2)^{29,30,32–40,42}. Similar cost savings have been observed in literature on SCIg. While the per-gram cost of SCIg drugs may be higher than that of intravenous immunoglobulin (IVIg), the overall cost-effectiveness of SC administration becomes apparent when factoring in additional administration and site of care fees^39,40. Finally, in contrast to IV infusions, some SC-delivered counterparts do not require the administration of pre-medications, resulting in additional cost of care savings. For example, the premedication cost of IV infusion therapy for rheumatoid arthritis delivered in hospital-based infusion center was $7 and $19 (2017 USD) per infusion for infliximab and rituximab, respectively^3,41.

Table 2. Summary of studies comparing direct and indirect costs associated with transitioning from intravenous to subcutaneous administration within-hospital or in a home-based setting.

Reference	Comparison	Design and Population	Findings
Parra 2023	IV versus SC	A systematic review of 34 publications on costs, HCRU, patient preferences, and administration time associated with daratumumab, rituximab, and trastuzumab in SC and IV presentations for patients with cancer	Compared with IV formulations, SC formulations of daratumumab, rituximab, and trastuzumab reduced preparation costs by 6.6%-50.1% and administration costs by 4.5%-95.3% when provided by a HCP in a clinical setting SC administration of rituximab and trastuzumab resulted in reduced productivity loss, including reduced travel expenses and time of informal caregivers
McCloskey 2023	IV versus SC	A systematic review of 72 publications of oncology biologics in a hospital setting	SC administration in a hospital setting reduced HCP time and resource use SC administration was associated with substantial time savings in the preparation and administration of treatment
Alsina 2022	IVIg versus SCIg	A cost-minimization model of annual costs per patient with PID from the Spanish National Healthcare System perspective (inpatient versus at home)	Annual costs per patient with PID were €4,266 ($4,731 USD) lower with SCIg versus IVIg, with differences primarily attributed to dosage (€1,927; $2137) and hospital administration costs (€2,688; $2,981), although SCIg was associated with training costs for home administration (€695; $771)
Harvey 2022	IV versus SC	A decision-analytic cost model assessing the incremental cost difference between IV and SC rituximab in a simulated cohort of patients with NHL in the US	20% transition rate in a cohort of 157 patients (769 total drug administrations) was predicted to save $153,000 from the payer perspective Increased provider capacity by 270 h At the cohort level, 20% transition freed 470 h of patient time
Ritchie 2022	IV versus SC	A population-based cohort study of 7,890 patients who received IgG for the treatment of immunodeficiency diseases in Canada	Average administration cost per year of self-administrated SC Ig was $5,386 lower than clinic-administered IVIg ($817 vs. $6,204) Switching just 50% of the patients from clinic-administered IV Ig to self-administered SC Ig could translate into $19.4 million in cost savings annually related to medical laboratory staff, nursing time, and ambulatory care visits
Slavcev 2021	IV versus SC	A prospective, cross-sectional, time-and-motion survey of relapsed/refractory multiple myeloma patients treated with daratumumab in Brazil, Greece, Israel, Japan, Poland, Sweden, Taiwan, and Ukraine	SC formulation reduced median total active HCP time by 63.8% for the first treatment and 49.5% for subsequent treatments Results extrapolated to two years estimated active HCP time per patient was reduced by 50% when using SC in comparison to IV Estimated chair time for SC administration was 97% lower than IV administration for initial (from 456.9 to 13.3 min) and subsequent treatments (238.0 to 8.1 min)
Perraudin 2020	IVIg versus SCIg	Swiss cost-minimization analysis for chronic inflammatory demyelinating polyneuropathy	Hospital-based IVIg cost health insurance payers 114,747 CHF over 48 weeks, versus SCIg costs of only 86,558 CHF ($126,221 USD vs. $95,213 USD)
Anderson 2019	IV versus SC	A systematic rapid evidence assessment of 63 publications assessing biologics for the treatment of malignancies	SC administration of biologics for the treatment of malignancies significantly reduced provider time spent on drug preparation and administration, resulting in lower costs compared to IV administration of the same agents
Mallick 2018	IVIg versus SCIg	Pooled analysis of six phase 3 studies of patients with Primary Immunodeficiency who switched from IVIg to SCIg	Patients in European and Japanese studies who switched from IVIg to SCIg reported significant and meaningful improvements in health status and IgG-specific HRQoL perception across all time points as measured by Life Quality Index domains (p < 0.0001)
De Cock 2016a	IV versus SC	A non-interventional time-and-motion study of patients across eight countries who received rituximab for the treatment of NHL	Significantly less mean active HCP time required to prepare and administer SC rituximab versus IV formulation (32% reduction; p < 0.0001) Mean chair time for patients was significantly lower with SC versus IV administration (74% reduction, p < 0.0001)
De Cock 2016b	IV versus SC	A prospective, observational time-and-motion study of patients across eight countries who received trastuzumab for the treatment of HER2-positive early breast cancer	Mean patient chair time was significantly reduced with SC single-use injection device (57 min saved; p < 0.0001) and with SC handheld syringe (55 min saved; p < 0.0001) versus IV formulation Mean active HCP time was significantly reduced with SC single-use injection device (13 min; p < 0.0001) and SC handheld syringe (17 min p < 0.0001) versus IV formulation
Olofosson 2016	IV versus SC	An observational study of HCRU among 195 patients (101 IV, 94 SC) with HER2-positive breast cancer in Sweden	IV trastuzumab requires 14 min & 23 min more for nurses and patients versus SC Significantly more patients treated with IV trastuzumab took time off from work compared to those on the SC regimen (14% vs. 5%; p = 0.0223) Personal and caregiver productivity loss and lost leisure time were also higher with IV versus SC delivery for initial and subsequent trastuzumab treatments (€140 higher and €16 higher, respectively) Societal costs were €897 lower per treatment with SC versus IV trastuzumab
Igarashi 2014	IV Ig versus SC Ig	A prospective phase 3 single-arm study of 24 Japanese patients with Primary Immunodeficiency who transitioned from IVIg to SCIg treatment	Switching to SCIg treatment was associated with a median productivity loss reduction of 60% from baseline to Week 12 and 24, resulting in a reduction in costs of JPY 10,875 per patient per month (approximately $80 USD) The number of patients, parents, or guardians who were not absent from work or housework duties and had no reduction in working time increased from 17.4% with IVIg treatment to 39.1% with SCIg treatment

Abbreviations: CHF = Swiss franc; HCP = Healthcare professional; HCRU = Healthcare resource utilization; HRQoL = Health-related quality of life; Ig = Immunoglobulin; IV = Intravenous; JPY = Japanese Yen; NHL = Non-Hodgkin lymphoma; SC = Subcutaneous; US = United States; USD = United States Dollar.

Indirect costs

In addition to benefits from direct HCRU and costs, SC dosing has been associated with reduced societal costs compared with IV administration methods, including hospital-related absenteeism and productivity loss, across many regions and disease areas, as outlined in six studies^{3,33–35,38,42}. Analogous to reductions observed in HCP time, studies also suggest SC treatment reduces time in-clinic for patients relative to IV treatments. In some cases, the savings are extremely meaningful, including 74% to 97% reductions in time, or hours equivalent to 11 weeks of full-time work (Table 2)^33,34,42. Beyond this, it is important to remember that indirect costs arising from productivity loss and lost leisure time apply to patient caregivers as well, further extending the potential economic benefits of transitioning to home-based sites of care with devices such as the novel OBDS^3,38.

Patient experience

On the topic of patient experience, 14 articles compared IV and SC administration, one compared SC and an OBDS, and five others were non-comparative^{5–9,13,21,28,31,44–55}. One study reported on HCRU and patient-experience and one systematic review included details on HCRU, indirect costs, and patient experience^37,44. Subcutaneous administration is safe and well-tolerated, with studies indicating that transitioning from IV to SC versions of some drugs may be associated with reduced infusion-related reactions. In a phase 3 trial comparing SC versus IV bortezomib administration for the treatment of relapsed/refractory multiple myeloma, peripheral neuropathy of any grade (38% versus 53%; p = 0.044), grade 2 or worse (24% versus 41%; p = 0.012), and grade 3 or worse (6% vs 16%; p = 0.026) was significantly less common with SC versus IV administration, respectively⁴⁹. The authors concluded that SC administration offered non-inferior efficacy as well as an improved safety profile relative to IV administration. In the phase 3 BELIS study of trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, patients reported more mild administration events with the SC treatment when compared to IV treatment¹³.

Most patients with chronic disorders express a preference for SC administration, primarily due to the convenience and comfort of treatment in home-based settings (HCP-administered or self-administration) and avoidance of inpatient care, reduced administration times/less interference with daily life, and greater independence compared with IV administration^31,50. In qualitative interviews of patients with systemic lupus erythematosus (SLE), 76% of patients expressed a preference for autoinjector SC administration of belimumab versus IV formulation, citing convenience, time saved, cost, and reduced injection pain as the primary reasons⁴⁷. Compared with IV administration, the SC autoinjector also improved the ability to work (reported by 59% of patients) and perform daily activities (40%). A cross-sectional survey of 200 U.S. physicians found >90% recommended SC administration of SLE drugs over IV administration for patients who live or work far away from an infusion center (98.9%), prefer SC administration (97.8%), are employed (93.3%), have an active lifestyle (91.8%), never or rarely miss medication doses (96.9%), and/or prefer autonomy and independence in treatment matters (95.3%)⁴⁶. Patients receiving oncology treatments also generally report a preference for SC versus IV administration^5,37,44,55. In the PHranceSCa (N = 160) study investigating the preferences of patients with HER2-positive early breast cancer, 85% favored SC administration of fixed-combination pertuzumab and trastuzumab (PH FDC SC) over IV pertuzumab and trastuzumab⁵⁵. The reasons cited by the 136 patients who preferred SC administration included reduced clinic time and enhanced comfort, with over 90% expressing a "very/fairly strong" preference for this mode. Additionally, SC administration was well tolerated, with no new safety signals reported versus IV infusion. These preferences extend beyond oncology to other therapeutic areas. A discrete choice experiment found patients with primary immunodeficiency show a preference for SCIg versus IVIg treatment, noting duration of side effects, frequency of treatment administration, and number of needles required for administration as the three most important attributes for therapy preference⁴⁸.

Further improving upon classic SC options, novel OBDS feature a hidden needle system, which may improve patient experience and compliance compared with IV and conventional SC administration. An international survey of 2,098 patients found that 63.2% experienced needle phobia and rated the intensity of their fear as 5.7 on a scale from 0 (no fear) to 10 (very strong/unreasonable fear or avoidance)⁴⁵. Almost all patients (89.7%) stated devices with invisible needles would reduce their needle fear. In alignment with these findings, 100% of patients with primary immunodeficiency treated with SCIg reported a preference for the novel OBDS device (Enable Injections enFuse®) over a constant flow rate syringe pump (Crono S-PID-50)²¹. Additionally, patients listed ease-of-use, increased mobility during infusion, reduced pain at the injection site, and shorter set-up time as key reasons for preferring the novel OBDS device over the syringe pump.

Payer primary market research

Payer demographics

Seventeen US payers involved in formulary decision making within their organizations participated in semi-structured interviews. The payers interviewed represent approximately 227 million covered lives, accounting for around two-thirds [68%] of the US population⁵⁶. Nine participants (53%) had a pharmacy director role at their organization and 8 held a medical director position (47%). Payers represented regional Managed Care Organizations (MCOs; 41.2%), national MCOs (23.5%), Integrated Delivery Networks (IDN; 11.8%), Pharmacy Benefits Managers (PBM; 11.8%), and Managed Medicaid (11.8%) stakeholders (Figure 3). All participants except for the two PBMs were involved in formulary decision making for both the medical and pharmacy benefit.

Figure 3. Overview of payer characteristics.

Abbreviations: IDN = Integrated Delivery Network; MCO = Managed Care Organization; PBM = Pharmacy Benefits Manager.

Value perception of the novel OBDS

Payers reported an overall positive clinical and economic value perception of the novel OBDS device. When asked about the perceived advantages of the novel OBDS, 70.6% of payers independently cited simplicity, ease-of-use, and convenience as the most beneficial features, with the potential to replace IV infusion by facilitating at-home HCP- or self- administration (52.9%) as the second most frequent unaided response. Compact size, ability to alleviate needle phobia, and reduced pain/discomfort compared with traditional SC injections were also highlighted as product strengths. When asked about important attributes of the novel OBDS for coverage decision-making, payers cited the flexibility to receive treatment at home via HCP- or self- administration or in-clinic as the main attribute. Other critical attributes included ease-of-use, reduced infusion chair time, absence of separate billing (due to the novel OBDS not being classified as separate medical equipment), and a hidden needle mechanism to potentially improve adherence (Figure 4). Immunology and oncology were most frequently cited as therapeutic areas in which the novel OBDS would have the greatest value proposition, although many stakeholders noted the value would depend on the paired medication rather than the disease state.

Figure 4. US payers’ (N = 17) ratings of the most important novel OBDS product attributes in payer coverage decision-making.

*Prompt: “On a scale from 1 to 5, where 1 = not important at all and 5 = extremely important, how important are the following attributes in your coverage decision-making?”. Abbreviations: HCP = healthcare professional; Med = median; NSI = needle stick injury; OBDS = on-body delivery system.

Most payers (88.2% from organizations representing 219.5 million lives) said the novel OBDS could fulfill unmet needs such as cost of IV infusion, convenient administration, and improved patient compliance in large-volume SC delivery by enabling safe, easy, self-administration. Compared with SC infusion pumps, the majority of payers (70.6% from organizations representing ∼190 million lives) reported that they have a more favorable view of the clinical value of the novel OBDS based on ease-of-use, small size, reduced pain at injection site, ability to replace in-person infusion, and potential to improve compliance.

Probable access and coverage decisions for the novel OBDS

Nearly all payers (88.2% from organizations representing 207.3 million lives) stated they would consider covering and managing pharmaceutical products packaged with the novel OBDS. The remaining two payers (11.8% from organizations representing 19.7 million lives) stated that they might look at the total cost of the combination product compared to the cost of other routes. The novel OBDS is considered a constituent to paired medications rather than separate medical equipment since it functions as the drug’s delivery platform; as such, the novel OBDS would likely be covered under the pharmacy benefit if the bundled drug is primarily self-administered or under the medical benefit if the drug requires HCP oversight. Payers indicated management of the novel OBDS would likely be aligned to the current policy or coverage criteria for the drug and would be the same across different books of business (e.g. Commercial, Medicare).

Price premium potential of the novel OBDS

A significant proportion of payers (82.4%) acknowledged a drug delivered via the novel OBDS could warrant a price premium above the cost of the standalone SC drug vial. Of this 82.4%, half stated that the premium would range from 5% to 20% while the other half cited an unspecified price premium that would be dependent on the individual drug situation. Payers noted this could be warranted by the novel OBDS’s ability to reduce costs associated with HCP-administered therapies and minimize time spent in infusion settings, and that clearly documented healthcare savings through a return on investment or superiority compared with other drug delivery could justify a higher price premium. Given the integrated nature of the novel OBDS as a drug-device combination, its associated costs are included in the total drug expense. Payers emphasized that the future economic valuation and subsequent pricing strategy for a medication incorporated with the OBDS as a combination product would affect the perceived value of the medication and acceptable price premium compared to a standalone SC vial.

Reimbursement and distribution of the novel OBDS

All payers surveyed on the potential role of the novel OBDS in promoting transitions in site of care (n = 12) stated that the novel OBDS could support the transition from in-clinic to home-based self-administration, attributed to the system’s ease of use and simplicity. Most payers (12 of 17; 70.6%) noted that their organizations have site of care preferences and steer their members to less expensive care settings such as outpatient infusion centres or home-based administration (HCP-administration or self-administration). Typically, payers’ strongest preference is to direct their members to home-based administration due to cost, but some payers will consider a host of factors for each member such as geographical access to clinics, acuity/severity of disease, and concerns for adverse events before redirecting members to a different site of care. While site of care preferences are critical for payers, their ultimate focus is on preventing hospitalization where possible. Payers generally anticipated there would be incentives to distribute the novel OBDS through a specialty pharmacy as it is highly likely to be used to deliver medications already dispensed through this route. Payers were willing to consider reimbursement of telehealth visits for initial training on the novel OBDS.

Discussion

This literature review was conducted to understand the value of SC drug administration using OBDS compared to IV or classic SC methods, including HCRU, indirect costs, and patient experience. Numerous studies emphasize the advantages of transitioning from inpatient IV drug administration to home-based (self- or HCP- administered) SC care for chronic health conditions, such as reduced HCRU and medical costs, lower rates of absenteeism, improved patient convenience and satisfaction, and better safety outcomes. Despite a wealth of published literature comparing IV with classic SC across these parameters, there was a notable dearth of evidence on the OBDS. As such, primary market research with US payers was required to fully assess potential benefits the novel delivery system could bring to the healthcare system.

Even with evident benefits and continually increasing pressures on healthcare systems, numerous medications with the potential for self-administration continue to be delivered in-clinic. For instance, the self-administration of SC romiplostim has been shown to be efficacious for treating adult patients with immune thrombocytopenia without compromising safety⁵⁷. While this mode of administration gained regulatory approval in the European Union back in 2018, it has yet to receive approval in the US. Similarly, self-administration of some biologics such as denosumab were temporarily granted in the US in response to the COVID-19 pandemic but were later withdrawn. The introduction of technology like the novel OBDS could promote the site of care transition by offering easy to use delivery of large-volume SC medications at home with or without the need for HCP supervision. This study is the first to describe the clinical and economic value of a novel large-volume SC OBDS from the payer’s perspective and outlines considerations for drug-device formulary decisions.

Intravenous drug administration has several strengths, including higher bioavailability and longer dosing intervals than SC administration methods such as needle and syringe or auto-injectors. However, comparative literature also demonstrates clear, consistent advantages for SC administration in terms of site of care flexibility (supporting improved accessibility to efficacious medicines and reductions in HCRU) and patient preference benefits (e.g. time-savings and comfort from self-administration independent of a clinic setting; Figure 5). Although there are distinct advantages and considerations for classic SC delivery methods, this research illustrates that the novel OBDS is well poised to meet all major areas of unmet needs of current SC devices, providing the same convenience benefits of auto-injectors with the volume capacity of a SC pump (Figure 5).

Figure 5. The evolution and relative benefits of drug delivery technologies.

^aFeasibility dependent on syringe volume and number of needle pricks/injection sites.

^bVaries by product (e.g. flexible [Enable Injections enFuse] versus fixed dosing [West SmartDose]).

When making coverage decisions, the 17 US payers surveyed valued product attributes that could lead to direct reductions in HCRU and associated costs when making coverage decisions. As such, flexibility in site of care emerged as the highly ranked attribute of the novel OBDS by payers, owing to its capacity for home-based care via HCP- or self-administration. In addition to reducing HCP oversight of treatment and patient time spent in-clinic to receive treatment, the novel OBDS is expected to further reduce costs associated with drug dispensing. By permitting medications to be dispensed through speciality pharmacies rather than an inpatient setting, the average markup of drugs paired with the novel OBDS may be lower than if administered through traditional SC routes; for example, the markup for abatacept in the hospital is approximately 90% higher over specialty pharmacies⁵⁸. Payers also appreciated features like ease-of-use and the hidden needle mechanism as these factors contribute to patient compliance. The user-friendliness of the novel OBDS allows patients to administer their medication without complications or extensive training, making the treatment process less daunting. Additionally, the hidden needle feature directly addresses common anxieties surrounding needle phobia and may reduce apprehensions associated with injections. Together, these features may enhance the overall treatment experience and subsequently improve adherence to treatment regimens. Further, offering a more positive and comfortable treatment process may increase the likelihood of patients’ consistently following prescribed drug schedules, potentially contributing to better health outcomes and reducing overall healthcare costs for payers. At these large SC delivery volumes, the distinction of the OBDS as a constituent of the drug, rather than separate medical equipment, simplifies the reimbursement process and may promote broader adoption.

The findings of this study indicate that a significant proportion of payers have established policies that guide their members to more economical site of care, such as outpatient infusion centers, home infusion, and the most desirable site of care: patient self-administration. A substantial proportion of payers expressed a willingness to consider coverage for pharmaceutical products integrated with the novel OBDS, and no payers surveyed would decline coverage for medications because they were paired with the novel OBDS. Instead, payers acknowledged the novel OBDS may warrant a price premium versus the standalone SC drug and certainly over the IV counterpart, underscoring the perceived clinical and economic value of this drug delivery method. To synthesize, our findings elucidate a dual-layered receptivity among payers towards the novel OBDS: a substantial willingness to cover pharmaceutical products integrated with it and a considerable openness to a price premium for innovative technologies which may reduce overall HCRU and associated costs.

Given that most payers interviewed in our study anticipate drugs packaged with the novel OBDS will be administered at home by patients or HCPs and receive coverage under a pharmacy benefit, it is plausible that similar cost-savings may be observed if drug-device combinations including the novel OBDS are added to the formulary. Moreover, by reducing the need for in-person SC injections and providing confidence with a safe, easy to use device, the novel OBDS is expected to reduce active HCP time and associated administration costs while also minimizing patient time spent undergoing treatment, travel costs, and workplace absenteeism for patients and their caregivers.

Limitations

The primary limitation is the relatively small cohort of payers (N = 17), although their policies impact over 227 million US enrolees (e.g. representing approximately 68% of the population)⁵⁶. Interviews were limited to US stakeholders reflecting subjective views rather than official positions of health insurance organizations, potentially limiting generalizability to other healthcare markets. Public payers who cover a substantial number of underserved and minority populations may also be underrepresented in the cohort. Furthermore, it should be noted that our findings may not be applicable to all therapeutic areas due to variations in payer channels, benefit designs, and other relevant factors. Additionally, the literature review, although not systematic, included relevant and up-to-date research. OBDS is an evolving field, suffering from a paucity of published research on economic impacts or payer perceptions. Ultimately, most reviewed studies compared the clinical, economic, and humanistic burden of SC drug delivery to inpatient IV drug delivery rather than at-home IV administration or conventional SC versus SC using OBDS. Additional research is needed to explore the direct and indirect savings realized from transitioning from IV or traditional SC to SC with OBDS and to further elucidate the potential added benefits of OBDS.

Conclusions

The clinical, economic, and humanistic benefits of SC drug administration and home-based (self- or HCP- administered) care depicted in the literature align with the priorities of US healthcare payers, as demonstrated by the perceived value of a novel OBDS. Payers believe the novel OBDS could facilitate the flexible administration of large-volume SC drugs in home-based or in-clinic setting due to its safe, simple, and easy to use design. Payers generally expect the combination product to warrant a price premium over the standalone SC drug cost and certainly over the IV counterpart, as it has the potential to offer substantial cost savings by minimizing HCRU, including time spent in infusion settings. Taken together, the novel OBDS offers undeniable value for healthcare systems, payers, clinicians, and patients alike. Additional studies investigating cost-savings would be helpful to further validate and quantify these findings.

Transparency

Author contributions

Mehul Desai was involved in the conception and design of the study as well as drafting and review of the manuscript. James Kenney, and Edmund Pezalla were involved in the drafting of the manuscript and revising it critically for intellectual content. All authors agree to be accountable for all aspects of the work.

Acknowledgements

Medical writing/editorial assistance was provided by Margaret Ainslie-Garcia and Jordan Donders, employees of EVERSANA.

Declaration of financial/other relationships

Mehul Desai is an employee of Enable Injections Inc. James Kenney and Edmund Pezalla received an honorarium from Enable Injections Inc. for their contributions to this research. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding for this work was provided by Enable Injections Inc. The study sponsor was involved in study design, data interpretation, and data review.