Budget impact model of a 5-grass sublingual immunotherapy tablet for the treatment of grass pollen-induced allergic rhinitis

Abstract

Objective:

Allergic rhinitis (AR) is a chronic disease with a substantial clinical and economic burden. This study estimated the potential budget impact (BI) associated with market entry of Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens Allergen Extract Tablet for Sublingual Use (‘5-grass SLIT tablet’) for patients aged 10–65 with grass pollen-induced AR.

Methods:

A budget impact model was constructed to estimate the potential BI from a US payer perspective. The model calculated pharmacy, medical, and total (pharmacy + medical) costs per-member-per-month (PMPM) with and without market entry of the 5-grass SLIT tablet, considering a 3-year time horizon. The target population was determined using an epidemiological approach and existing literature. The treatment market shares without 5-grass SLIT tablet entry were derived from an analysis of de-identified insurance claims data. Pharmacy costs and medical utilization rates and costs were obtained from the claims data analysis and existing literature. One-way sensitivities were conducted for key model inputs.

Results:

Using an illustrative example of a hypothetical health plan with one million members, the estimated target population of AR patients aged 10–65 was 26,320. On a PMPM basis, pharmacy costs increased by $0.36, $0.44, and $0.51, while total costs (after medical cost offsets) increased by $0.15, $0.18, and $0.22 in the first, second, and third years following entry of the 5-grass SLIT tablet, respectively. Results were most sensitive to changes in the compliance rate, treatment duration, and price. The BI will vary from the base case example when alternative, payer-specific inputs are used.

Conclusions:

Using base case inputs, use of the 5-grass SLIT tablet to treat grass pollen-induced AR increased the pharmacy budget for a hypothetical third-party payer. Higher pharmacy costs were partially offset by lower medical budget due to reduced resource use compared with existing treatments.

Keywords::

• Budget impact model
• Allergen immunotherapy
• Allergic rhinitis
• Sublingual immunotherapy

Introduction

Allergic rhinitis (AR) is one of the most common chronic diseases, affecting between 10–40% of the US population1–3. AR is induced by seasonal or perennial aeroallergens, including grass pollen, dust mites, tree and weed pollen, animal dander, and mold spores2^,4. AR is commonly characterized by sneezing, congestion, and rhinorrhea and is often accompanied by symptoms of allergic conjunctivitis2^,5. It is additionally associated with a number of comorbidities, such as sinusitis, nasal polyps, chronic pharyngitis and nasal pharyngitis, and asthma4–6. While figures vary across studies, ∼40% of AR patients also have asthma7^,8. Longitudinal and birth cohort studies acknowledge a temporal relationship between rhinitis and asthma, with asthma clinically manifesting later in life than rhinitis7^,9–11. Rhinitis in patients who do not have asthma is a risk factor for developing asthma in both adults and children12. The manifestations of AR and its associated comorbidities may impede daily activities, reduce quality of sleep, and affect productivity, resulting in a significant clinical and economic burden for patients4^,5. A 2005 study estimated that the annual healthcare system-related costs related to AR were $11.2 billion, with more than $5.6 billion spent on prescription medication5. Additionally, a 2006 study estimated the annual workplace burden of lost productivity related to AR to be $593 per employee, higher than any of the other conditions assessed, including depression, diabetes, and asthma13.

Treatment options for AR include avoidance of exposure to allergens, pharmacological treatment of symptoms with agents such as antihistamines and corticosteroids, and allergen immunotherapy (AIT). AIT is the only existing therapy that is considered disease-modifying14–17. In the US, it is available as subcutaneous immunotherapy (SCIT) and, as of April 2014, as sublingual immunotherapy (SLIT) tablets. Liquid SLIT is approved widely in Europe but not in the US. In a 2003 Cochrane review of 22 trials, liquid and tablet SLIT was found to significantly reduce symptoms and medication requirements of AR; a later review of 60 trials reinforced this finding14^,18. A 2007 Cochrane review of 51 trials similarly found that SCIT significantly reduced symptom scores and medication use among patients with seasonal AR19, and a 2010 meta-analysis of 19 trials comparing SLIT to placebo for grass pollen-induced AR found that SLIT was effective in reducing symptoms and medication use20. Another recent study comparing 20 placebo-controlled trials of SCIT and two grass pollen SLIT tablets, Grazax® and Oralair®, found at least similar efficacy (standardized mean difference in AR symptom control) and cost savings associated with Oralair® relative to both other treatments21.

In addition to short-term benefits, AIT has been shown to have a long-term effect: in a randomized study of patients with grass pollen-induced AR, SCIT was shown to provide sustained clinical benefit and decreased immunologic reactivity for several years following discontinuation22. Another randomized study of patients with grass pollen-induced AR found that a tablet SLIT product remained effective 2 years following discontinuation16. AIT has additionally been shown to positively impact asthma-related outcomes: a Cochrane review of 75 trials of SCIT concluded that AIT reduces asthma symptoms, use of asthma medications, and bronchial hyper-reactivity23. A Cochrane review of 25 trials of liquid SLIT found that SLIT reduces the need for medication for allergy combinations (asthma together with rhinitis and conjunctivitis), reduces allergic symptoms (when analyzed together with asthma symptoms), reduces the composite symptom plus medication score for allergies together, and improves FEV1% and FEF25–75% respiratory function test results24. A systematic review of published studies on the health economics of AIT found that 23 of 24 relevant studies demonstrated that the use of AIT resulted in cost savings when compared with the use of pharmacologic therapy25; a Health Technology systematic review of AIT for AR found both SCIT and SLIT (liquid and tablets) to be cost-effective from ∼6 years compared with symptomatic therapy26.

Despite these clinical and economic benefits, studies suggest that a low percentage of patients who would benefit from AIT receive it27^,28. The increased availability of sublingual formulations of AIT may offer the potential to reach more patients. However, these new treatments must be evaluated within the context of their cost to payers.

This study developed a model that can be populated with data from third party payers in order to estimate the potential budget impact (BI) of Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens Allergen Extract Tablet for Sublingual Use (‘5-grass SLIT tablet’) for patients aged 10–65 with grass pollen-induced AR, with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for any of the five grasses contained in the product29.

Methods

Model overview

The budget impact model (BIM) was developed to estimate the potential economic impact, from a US payer perspective, associated with market entry of the 5-grass SLIT tablet, which is indicated for the treatment of patients aged 10–65 with grass pollen-induced AR, with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for any of the five grasses contained in the product (Figure 1). The model calculates the pharmacy, medical, and total (pharmacy + medical) cost with and without market entry of the 5-grass SLIT tablet, considering a time horizon of 3 years following market entry. Results can be calculated in terms of the total annual incremental BI in 2013 US dollars for the target population, as well as BI on a per-member-per-month (PMPM) basis. The results presented in this article are based on an illustrative example using a set of base case inputs and assumptions for a hypothetical health plan with one million members; results are expected to vary with data inputs from different payers.

Figure 1. Model framework.

Key assumptions

The model was constructed from a US third-party payer perspective; as such, it considered those pharmacy and medical costs borne by payers. The target population for the model was assumed to be the population for which the 5-grass SLIT tablet is indicated: patients aged 10–65 with grass pollen-induced AR, with or without conjunctivitis. Because the illustrative example BI was presented at discrete time points and over a short time horizon (3 years following market entry), no discounting was used30. The treatment mix without entry of the 5-grass SLIT tablet was derived from an analysis of private insurance claims data, in which the market share of each available treatment combination was estimated as the percentage of patients taking that treatment combination over a 1-year period. Treatments approved after approval of the 5-grass SLIT tablet were not included in the treatment mix. Projected market shares with entry were derived from these estimates and adjusted based on assumptions regarding the use of the 5-grass SLIT tablet as either replacement or add-on therapy for existing treatment combinations. Patients utilizing SCIT, either as monotherapy or in combination with other treatments, were assumed not to switch to the 5-grass SLIT tablet or to use it as an add-on therapy in addition to SCIT. Per the approved indication, patients were assumed to initiate the 5-grass SLIT tablet 4 months prior to the start of grass-pollen season and to continue to take it during the season, which was assumed to be 2 months long. Patients were assumed to be 100% compliant to therapy for all treatment combinations included.

Base case model inputs

Model inputs were derived from either the medical, scientific, and pharmacoeconomic literature or an analysis of private insurance claims data. The published clinical and scientific literature used for the base case model inputs related to the target population, market share of the 5-grass SLIT tablet, duration of allergy season, price of the 5-grass tablet, price of epinephrine auto-injectors, dispensing fee, average co-pay for medications based on tiers, and medical utilization rates is described in the following sections. The analysis of private insurance claims data was used to estimate base case model inputs for market shares of treatments, monthly costs of treatments, and unit costs for medical services. The insurance claims analysis utilized the OptumHealth Reporting and Insights claims database, which includes de-identified data regarding prescription drug and medical services for ∼18 million employees and dependents from 82 self-insured large companies with locations across the US and operations in a broad array of industries and job classifications. The data contain complete medical and prescription drug claims for all beneficiaries, including employees, spouses, dependents, and retirees, and are current through Q1 2013.

Target population

A prevalence-based approach was used to estimate the size of the target population, patients aged 10–65 with grass pollen-induced AR, with or without conjunctivitis (Table 1). The covered population was assumed to comprise one million individuals. The proportion of covered patients aged 10–65 was calculated using the estimated US population age distribution in 201231. The proportion of patients aged 10–65 with AR was derived from rates of hay fever among children and adults reported in the 2011 National Health Interview Survey32^,33. The proportion of patients whose AR was induced by grass pollen was assumed to be equal to the share of individuals with hay fever who were sensitized to rye grass, as reported in the 2005–2006 National Health and Nutrition Examination Survey1. Finally, the annual increase in the target population was set equal to the annual increase among 13–14-year-olds with rhinitis in the US, as reported in the International Study of Asthma and Allergies in Childhood34. The increase in prevalence was assumed to be applicable to the entire target population (i.e., beyond children).

Table 1. Target population.

Parameter	Percentage of previous row	Number of patients	Sources
Covered population		1,000,000	Assumption
Patients aged 10–65^a	74.50%	744,996	US Census Bureau31
Patients aged 10–65 who were diagnosed with AR in the past year^b	7.99%	59,548	Bloom et al.32; Schiller et al.33
Patients aged 10–65 who were diagnosed with AR and are allergic to grass pollen^c	44.20%	26,320	Salo et al.1
Total target population		26,320

^aCensus population estimate as of July 1, 2012.

^bChildren (between the ages of 10–17) who had AR during the past year and adults who reported a diagnosis of AR during the past year as told by a physician or healthcare professional. Estimates weighted by US census data to account for the proportion of patients in each age range to create a weighted average.

^cBased on the percentage of patients with AR with detectable levels of allergen-specific IgEs for rye grass among a representative sample of the US population.

Market shares with and without the 5-grass SLIT tablet

The model considered the following existing treatments for grass pollen-induced AR: SCIT, intranasal steroids (INS), ophthalmic anti-allergics, antihistamines, and montelukast. The model also considered that patients may receive over-the-counter (OTC) treatment only or no treatment at all. Base case market shares without entry of the 5-grass SLIT tablet were derived from the distribution of treatment combinations used by relevant patients in the OptumHealth database, as observed in the most recent year of available claims data (April 1, 2012 to March 31, 2013). To be included in the claims analysis, patients were required to have at least one diagnosis for AR due to pollen (ICD-9-CM code 477.0) during the year prior to the observation year (April 1, 2011 to March 31, 2012). During the observation year, patients were required to be aged 10–64, to have had continuous enrollment in an insurance plan observed in the OptumHealth database, and to have had at least one medical visit. Patients meeting these criteria (n = 54, 307) were categorized based on treatments taken during the observation year (i.e., ranging from no treatment or OTC treatment only to all five types of available pharmacotherapy). Without entry of the 5-grass SLIT tablet, market shares of existing treatment combinations were assumed to be the same in each of the 3 years modeled.

Market shares with entry of the 5-grass SLIT tablet were derived from the OptumHealth claims analysis and adjusted based on several assumptions. First, 10% of the target population was assumed to take the 5-grass SLIT tablet in the first year post-entry, followed by 12% in the second year and 14% in the third year. This assumption was informed by the share of patients using SLIT in other countries: in Spain, 18.3% of AR patients receive SLIT, and, in the UK, 15% of physicians report using SLIT35^,36. Second, because many AR patients are sensitized to multiple types of allergens (‘poly-sensitized’), a proportion of patients were assumed to use the 5-grass SLIT tablet in addition to existing pharmacologic treatment. In clinical trials for the 5-grass SLIT tablet, 65% of patients were sensitized to the 5-grass pollen allergen extract and at least one other unrelated allergen29. Consequently, the base case for this model assumed that 65% of AR patients treated with the 5-grass SLIT tablet would use it as an add-on to existing pharmacological therapy, while for the 35% of patients allergic only to grass pollen, the 5-grass SLIT tablet would replace their existing pharmacological therapy. Third, where the 5-grass SLIT tablet replaced patients’ existing pharmacological therapy, it was assumed that the market share of the existing therapy would be reduced in proportion to the treatment’s market share prior to entry of the 5-grass SLIT tablet. Finally, the 5-grass SLIT tablet was assumed not to replace or be used in addition to treatment combinations that include SCIT; consequently, SCIT-related medical budget was not impacted by the introduction of the 5-grass SLIT tablet. Table 2 reports the base case market shares in the 3 years with and without market entry of the 5-grass SLIT tablet.

Table 2. Base case market share with and without the 5-grass SLIT tablet.

	Market share without 5-grass SLIT tablet^a			Market share with 5-grass SLIT tablet^b
	Year 1	Year 2	Year 3	Year 1	Year 2	Year 3
5-grass SLIT tablet	0.00%	0.00%	0.00%	10.00%	12.00%	14.00%
Untreated or OTC	40.83%	40.83%	40.83%	38.76%	38.35%	37.94%
SCIT	14.09%	14.09%	14.09%	14.09%	14.09%	14.09%
INS	12.60%	12.60%	12.60%	11.97%	11.84%	11.71%
Ophthalmic anti-allergic	0.70%	0.70%	0.70%	0.66%	0.66%	0.65%
Antihistamine	3.12%	3.12%	3.12%	2.96%	2.93%	2.89%
Montelukast	3.19%	3.19%	3.19%	3.03%	3.00%	2.97%
SCIT + INS + Ophthalmic anti-allergic + Antihistamine + Montelukast	0.17%	0.17%	0.17%	0.17%	0.17%	0.17%
SCIT + INS + Ophthalmic anti-allergic + Antihistamine	0.28%	0.28%	0.28%	0.28%	0.28%	0.28%
SCIT + INS + Ophthalmic anti-allergic + Montelukast	0.25%	0.25%	0.25%	0.25%	0.25%	0.25%
SCIT + INS + Antihistamine + Montelukast	0.80%	0.80%	0.80%	0.80%	0.80%	0.80%
SCIT + Ophthalmic anti-allergic + Antihistamine + Montelukast	0.08%	0.08%	0.08%	0.08%	0.08%	0.08%
INS + Ophthalmic anti-allergic + Antihistamine + Montelukast	0.14%	0.14%	0.14%	0.13%	0.13%	0.13%
SCIT + INS + Ophthalmic anti-allergic	0.56%	0.56%	0.56%	0.56%	0.56%	0.56%
SCIT + INS + Antihistamine	1.82%	1.82%	1.82%	1.82%	1.82%	1.82%
SCIT + INS + Montelukast	1.75%	1.75%	1.75%	1.75%	1.75%	1.75%
SCIT + Ophthalmic anti-allergic + Antihistamine	0.15%	0.15%	0.15%	0.15%	0.15%	0.15%
SCIT + Ophthalmic anti-allergic + Montelukast	0.15%	0.15%	0.15%	0.15%	0.15%	0.15%
SCIT + Antihistamine + Montelukast	0.50%	0.50%	0.50%	0.50%	0.50%	0.50%
INS + Ophthalmic anti-allergic + Antihistamine	0.30%	0.30%	0.30%	0.28%	0.28%	0.28%
INS + Ophthalmic anti-allergic + Montelukast	0.27%	0.27%	0.27%	0.25%	0.25%	0.25%
INS + Antihistamine + Montelukast	0.91%	0.91%	0.91%	0.87%	0.86%	0.85%
Ophthalmic anti-allergic + Antihistamine + Montelukast	0.06%	0.06%	0.06%	0.06%	0.06%	0.06%
SCIT + INS	5.98%	5.98%	5.98%	5.98%	5.98%	5.98%
SCIT + Ophthalmic anti-allergic	0.51%	0.51%	0.51%	0.51%	0.51%	0.51%
SCIT + Antihistamine	1.77%	1.77%	1.77%	1.77%	1.77%	1.77%
SCIT + Montelukast	2.00%	2.00%	2.00%	2.00%	2.00%	2.00%
INS + Ophthalmic anti-allergic	0.80%	0.80%	0.80%	0.76%	0.75%	0.74%
INS + Antihistamine	2.67%	2.67%	2.67%	2.54%	2.51%	2.48%
INS + Montelukast	2.62%	2.62%	2.62%	2.49%	2.46%	2.43%
Ophthalmic anti-allergic + Antihistamine	0.20%	0.20%	0.20%	0.19%	0.19%	0.19%
Ophthalmic anti-allergic + Montelukast	0.14%	0.14%	0.14%	0.13%	0.13%	0.13%
Antihistamine + Montelukast	0.61%	0.61%	0.61%	0.58%	0.57%	0.57%

^aBase case market shares without entry of the 5-grass SLIT tablet were derived from an analysis of the OptumHealth database (April 1, 2012 to March 31, 2013).

^bAssumptions about market share of the 5-grass SLIT tablet after market entry were based on market shares of SLIT in other countries35^,36. The base case for this model assumed that 65% of AR patients treated with the 5-grass SLIT tablet would use it as an add-on to existing pharmacological therapy29. The 5-grass SLIT tablet was assumed not to replace or be used in addition to treatment combinations that include SCIT. Where the 5-grass SLIT tablet replaced patients’ existing pharmacological therapy, it was assumed that the market share of the existing therapy would be reduced in proportion to the treatment’s market share prior to entry of the 5-grass SLIT tablet.

Pharmacy costs

For each treatment, yearly total pharmacy costs from the payer’s perspective (Table 3) were calculated as payer-borne costs (average drug cost, dispensing fee, prior authorization [PA] cost, and step edit cost), less manufacturer-borne costs (payer rebates) and patient-borne costs (co-payment), using the following formula:

Table 3. Base case pharmacy costs.

Treatment	Average cost per month^a	Average months per year prior to allergy season^b	Average months per year during allergy season^b	Compliance rate	Actual months of use per year	Co-payment^a	Dispensing fee per fill^a	Yearly total drug cost
INS	$53.05	0	2	100%	2	$9.02	$1.69	$91.44
Ophthalmic anti-allergic	$107.74	0	2	100%	2	$15.05	$1.69	$188.75
Antihistamine	$60.32	0	2	100%	2	$9.81	$1.69	$104.40
Montelukast	$91.79	0	2	100%	2	$11.87	$1.69	$163.23
Untreated or OTC pharmacotherapy only	$0.00	0	0	100%	0	$0.00	$1.69	$0.00
5-grass SLIT tablet	$300.00	4	2	100%	6	$56.12	$1.69	$1473.42
Epinephrine auto-injector dual pack^c (yearly cost)	$262.69	1	0	100%	1	$56.12	$1.69	$208.26

^aAverage cost per month and co-payment for INS, ophthalmic anti-allergics, antihistamines, and montelukast were based on the OptumHealth Reporting and Insight claims analysis. The dispensing fee per fill was based on an average of the dispensing fee for branded and generic drugs for a 30-day retail supply37.

^bAverage duration of treatment (both prior to and during the allergy season) for the 5-grass SLIT tablet was based on the results of a US study in 473 adults aged 18 through 65 years.29

^cYearly epinephrine auto-injector cost was based on average of Red Book® price data for various epinephrine auto-injector dual pack products, as of February 10, 201438. For 5-grass SLIT tablet patients only, one epinephrine auto-injector fill per year was assumed.

Because the duration of the grass allergy season varies with geographic location, the base case assumed a 2-month allergy season. Therefore, patients taking symptomatic treatments (INS, ophthalmic anti-allergics, antihistamines, and montelukast) were assumed to receive treatment for 2 months. Patients taking the 5-grass SLIT tablet were assumed to receive treatment for 4 months prior to the start of the allergy season and during the 2-month season, consistent with the approved indication29. Treatments were assumed to be dispensed every 30 days and all patients were assumed to be 100% compliant to treatment.

For existing treatments, average cost per month (inclusive of co-payment) was calculated from the OptumHealth claims analysis. For the 5-grass SLIT tablet, the average cost per month was assumed to be $300 and the average co-payment was assumed to be $56.12, the average 30-day patient co-pay for non-preferred brand drugs in a three-tier plan as of 201337. Because it is recommended that an epinephrine auto-injector be prescribed in conjunction with the 5-grass SLIT tablet, patients using the 5-grass SLIT tablet were assumed to fill one prescription for an epinephrine auto-injector per year29. The yearly cost of an epinephrine auto-injector was based on an average of wholesale acquisition cost (WAC) data for various epinephrine auto-injector dual pack products, and the average co-payment was also assumed to be $56.1238. For all treatments, the base case dispensing fee per fill was based on the average 30-day retail dispensing fees for branded and generic drugs as of 201337. The base case assumed no rebates, PA costs, or step edit costs.

Medical costs

The yearly medical costs associated with each treatment were calculated as the total costs associated with the following categories of resource use: all-cause inpatient stays, AIT-related outpatient visits, non-AIT-related outpatient visits, and allergy tests. Total cost per year was calculated based on per-unit utilization costs, calculated as part of the OptumHealth claims analysis, and corresponding utilization data. Monthly utilization data for all-cause inpatient stays, AIT- related outpatient visits, and non-AIT-related outpatient visits were obtained from a published study of insurance claims data from Florida Medicaid patients39. Medical service utilization among Medicaid patients may be different than utilization among privately insured patients (e.g., a lower income population may have a different health profile); however, no adjustments were made in the model. Utilization rates were reported separately for children (<18 years) and adults (18 years and older), stratified by treatment with AIT. The original utilization rates were weighted according to the estimated US population age distribution31 in order to account for the proportion of patients in each age group. Utilization rates for patients receiving treatment combinations that include SCIT were set equal to those for AIT-treated patients, while utilization rates for patients receiving other existing pharmacological treatments, OTC treatment only, or no treatment were set equal to those for non-AIT-treated patients (Table 4). For patients receiving treatment combinations that include the 5-grass SLIT tablet, the numbers of inpatient stays and non-AIT-related outpatient visits were assumed to be equal to those for patients treated with SCIT, while the number of AIT-related outpatient visits was assumed to be 2 per year. Patients treated with SCIT or the 5-grass SLIT tablet were assumed to receive one allergy test over the 3-year period modeled, while patients receiving other existing pharmacological treatments, OTC treatment only, or no treatment were assumed not to receive any allergy tests.

Table 4. Resource utilization by encounter and treatment type.

Resource use	Children (<18 years)	Adults (≥18 years)	Source
SCIT
Number of inpatient stays per month	0.002	0.010	Hankin et al.39
Number of AIT-related outpatient visits per month	1.322	0.789	Hankin et al.39
Number of non-AIT outpatient visits per month	1.267	1.251	Hankin et al.39
Number of allergy tests per month	0.028	0.028	Assumption
Antihistamines/INS/Montelukast/Untreated/OTC
Number of inpatient stays per month	0.001	0.006	Hankin et al.39
Number of AIT-related outpatient visits per month	0.000	0.000	Hankin et al.39
Number of non-AIT outpatient visits per month	2.185	1.794	Hankin et al.39
Number of allergy tests per month	0.000	0.000	Assumption
5-grass SLIT tablet
Number of inpatient stays per month	0.002	0.010	Assumption
Number of AIT-related outpatient visits per month	0.167	0.167	Assumption
Number of non-AIT outpatient visits per month	1.267	1.251	Assumption
Number of allergy tests per month	0.028	0.028	Assumption

For each type of encounter, monthly resource utilization was multiplied by the relevant per-unit utilization cost obtained from the OptumHealth claims analysis. AIT-related outpatient visits were identified based on procedure codes used in the claims analysis of Florida Medicaid patients (CPT codes 95115, 95117, 95120, 95125, 95144, 95165, 95180, and 95199)39; all other outpatient visits were categorized as non-AIT-related. The average costs associated with each type of encounter were $6329.89 for an inpatient stay, $38.95 for an AIT-related outpatient visit, $191.61 for a non-AIT-related outpatient visit, and $127.90 for an allergy test. Based on these per-unit utilization costs and monthly utilization rates, total medical cost per month was calculated to be $334.54 for patients receiving treatment combinations that include SCIT; $387.27 for patients receiving other existing pharmacological treatments, OTC treatment only, or no treatment; and $307.34 for patients receiving treatment combinations that include the 5-grass SLIT tablet.

Sensitivity analyses

One-way sensitivity analyses were conducted to assess the impact of variations in key model inputs, including target population; price, market share, and treatment duration of the 5-grass SLIT tablet; overall compliance; and the share of patients who were poly-sensitized and consequently assumed to use the 5-grass SLIT tablet in addition to existing pharmacological therapy.

Results

In this illustrative base case example of the use of the BIM using a hypothetical health plan with one million members, the estimated target population of AR patients in the first year following market entry of the 5-grass SLIT tablet was 26,320 individuals. In the base case, the total BI in the first year after entry was $1,842,019, which comprised an increase of $4,366,539 in the pharmacy budget and a decrease in the medical budget of $2,524,520. The total BI in the second and third year after entry was $2,214,623 and $2,588,636, respectively. On a PMPM basis, pharmacy costs increased by $0.36, $0.44, and $0.51 PMPM, while total costs (after medical cost offsets) increased by $0.15, $0.18, and $0.22 PMPM in the first, second, and third years following market entry, respectively. The increase in BI in years 2 and 3 relative to year 1 is due to the assumed increase in the size of the target population. Detailed BI results are reported in Table 5.

Table 5. Budget impact (2013 USD).

	Year 1	Year 2	Year 3
Total budget impact
Pharmacy
Without 5-grass SLIT tablet	$1,962,528	$1,966,257	$1,969,993
With 5-grass SLIT tablet	$6,329,067	$7,216,059	$8,106,399
Incremental	$4,366,539	$5,249,802	$6,136,406
Medical
Without 5-grass SLIT tablet	$117,181,331	$117,403,976	$117,627,043
With 5-grass SLIT tablet	$114,656,811	$114,368,796	$114,079,272
Incremental	−$2,524,520	−$3,035,180	−$3,547,771
Total
Without 5-grass SLIT tablet	$119,143,859	$119,370,233	$119,597,036
With 5-grass SLIT tablet	$120,985,878	$121,584,855	$122,185,672
Incremental	$1,842,019	$2,214,623	$2,588,636
PMPM budget impact
Pharmacy
Without 5-grass SLIT tablet	$0.164	$0.164	$0.164
With 5-grass SLIT tablet	$0.527	$0.601	$0.676
Incremental	$0.364	$0.437	$0.511
Medical
Without 5-grass SLIT tablet	$9.765	$9.784	$9.802
With 5-grass SLIT tablet	$9.555	$9.531	$9.507
Incremental	−$0.210	−$0.253	−$0.296
Total
Without 5-grass SLIT tablet	$9.929	$9.948	$9.966
With 5-grass SLIT tablet	$10.082	$10.132	$10.182
Incremental	$0.154	$0.185	$0.216

In order to assess the impact of various model inputs, a series of one-way sensitivities was conducted on the following key parameters: target population (±20%), price of the 5-grass SLIT tablet (±20%), market share of the 5-grass SLIT tablet (±20%), treatment duration with the 5-grass SLIT tablet (±20%), compliance rate for all treatments (−20%), and share of patients treated with the 5-grass SLIT tablet who were poly-sensitized (lower bound: 0%, upper bound: 100%). Figure 2 presents the PMPM BI resulting from changes in these parameters in the first year following market entry of the 5-grass SLIT tablet; results in the second and third years were similar. Results were most sensitive to changes in the compliance rate, treatment duration with the 5-grass SLIT tablet, and price of the 5-grass SLIT tablet, which resulted in changes of ∼60%, 50%, and 40% to the PMPM BI, respectively. Changes to the target population size and to the market share of the 5-grass SLIT tablet were reflected proportionately in the BI, as they represented linear changes to the number of patients receiving treatment with the 5-grass SLIT tablet and, therefore, to the BI calculation. Changing the share of patients treated with the 5-grass SLIT tablet who were poly-sensitized had a minimal impact on the BI.

Figure 2. Sensitivity analysis of total PMPM costs with ±20% variation from base case inputs – Year 1. For the overall compliance rate, the sensitivity analysis only considered a low input of 80% relative to the base case of 100%. For the percent poly-sensitized among 5-grass SLIT tablet users, the sensitivity analysis considered 0% and 100% relative to the base case of 65%.

Discussion

As with all economic models, the results of this study are contingent upon the assumptions applied and the inputs used. Where assumptions were required, efforts were made to select those assumptions that were expected to most closely approximate real-world practice. However, some assumptions are likely not to mirror real-world events. For example, in this model, patients were assumed to be 100% complaint to treatment, which may lead to an over-estimate of the pharmacy costs associated with certain treatments. A sensitivity analysis of the compliance rate of 80% for all treatments reduced the total PMPM costs in year 1 from $0.15 to $0.06. In this model, patients receiving treatments other than the 5-grass tablet and SCIT (antihistamines, INS, montelukast, OTC treatments) and untreated patients were assumed not to receive any allergy testing, which may not reflect real-world practice. Additionally, patients treated with the 5-grass tablet were assumed to have 2 AIT-related outpatient visits per year; in real-world practice, allergists may schedule more than 2 visits per year for immunotherapy follow-up.

Furthermore, certain inputs were based on prescribing information, internal data, clinical trial data, or published literature, rather than real-world practice. The clinical trial population from which the rate of poly-sensitization was derived was subject to inclusion criteria and may not be representative of the larger population of AR patients, for instance due to geographic variation in the presence of specific allergens. Relatedly, particularly for patients primarily sensitized to pollen, treatment duration will vary geographically with the length of the allergy season, which depends on plant pollination cycles. The size of the target population was estimated based on the prevalence of AR as diagnosed by physician in the previous year and based on the rate of sensitization to grass pollen among AR patients; however, patients who are sensitized to a specific allergen may not necessarily be symptomatic and seeking treatment. Similarly, the annual increase in the prevalence of AR was derived from a survey of adolescents; the rate of increase among adult patients may be different. Consequently, the target population may be smaller in reality than modeled. Market shares for treatments preceding the introduction of the 5-grass tablet were derived from an analysis of insurance claims in a privately-insured population; as such, they may not reflect the treatment mix in the general population. Additionally, these inputs rely on coding accuracy; it is possible that the ICD-9-CM code for AR due to pollen (477.0) is incorrectly used for patients with AR induced by other allergens. Market shares following introduction of the 5-grass SLIT tablet were estimated using European data, and prescribing practices may differ between physicians in the US and in Europe. Similarly, the assumption that treatment with the 5-grass SLIT tablet would not replace existing SCIT treatment may not hold.

Adverse events were not considered in the model; consideration of adverse events and complications arising from treatment would likely increase the medical costs associated with certain treatments. The constructed BIM may under-estimate potential medical cost offsets related to the 5-grass SLIT tablet. Because AIT could be disease-modifying, studies have shown not only short-term but also long-term benefits22. Moreover, the model did not consider potential resource use or cost reductions related to AR-related comorbidities, such as asthma.

Conclusions

The BIM was developed to allow payers to estimate the economic impact of market entry of the 5-grass SLIT tablet approved for use in the treatment of patients aged 10–65 with grass pollen-induced AR, with or without conjunctivitis, using payer-specific data. In this illustrative base case example of a BI analysis using the model, use of the 5-grass SLIT tablet to treat grass pollen-induced AR demonstrated an increase in the pharmacy budget for a third-party payer. The increase in pharmacy costs is partially offset by a decrease in medical budget, due to reduced frequency of medical visits compared with symptomatic treatments and SCIT. As stated previously, the BI associated with entry of the 5-grass SLIT tablet will vary from the illustrative base case example provided here when alternative, payer-specific data are used.

Transparency

Declaration of funding

Funding for the development of this budget impact model was provided by Greer Laboratories, Inc. The study sponsor provided input on study design, reviewed the study results, and provided input on the manuscript.

Declaration of financial/other relationships

JI, HGB, S. Kelkar, and S. King are employees of Analysis Group, Inc., which received funding from Greer Laboratories, Inc., for this study. RP is an employee of Greer Laboratories, Inc., which sponsored the study. At the time of the study, RL was an employee of Greer Laboratories, Inc., and SH was a consultant to Greer Laboratories, Inc.

Acknowledgments

The authors gratefully acknowledge the contributions of Melissa Diener and Stephanie Bean, who were employees of Analysis Group, Inc. at the time of the study, to the development of the budget impact model.