Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark

Abstract

Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT.

Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3–5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out.

Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis.

Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT.

Keywords:

• Cost-minimization
• Allergy immunotherapy
• House dust mite
• HDM sublingually administered allergy immunotherapy tablet

Introduction

Worldwide there is an increasing prevalence of respiratory allergic disease (RAD) including allergic rhinitis (AR) and allergic asthma (AA), with AR being the most prevalent disease affecting an average of ∼25% of the European population. Allergy towards house dust mites (HDMs) may result in symptoms affecting the entire respiratory system, thereby causing a RAD. Approximately 50% of all patients with HDM RAD have both AR and AA¹.

The increasing prevalence in RAD is associated with an increasing burden to society, affecting the quality-of-life among patients, but also constitutes a substantial cost to the individual patient, the healthcare system, and society^2,3.

For patients with persistent moderate-to-severe HDM AR despite use of symptom-relieving medication, allergy immunotherapy (AIT) is the only treatment that treats the underlying disease instead of only providing short-term relief, which is associated with pharmacotherapy. Standard of care of AIT is currently subcutaneous injections (subcutaneously administered immunotherapy; SQ SCIT; Alutard SQ) with controlled doses of standardized natural allergens. During the treatment the immune system is gradually desensitized resulting in the patient becoming tolerant to the allergen previously triggering the allergic disease. Due to the treatment course of SQ SCIT the treatment is associated with inconvenience to the patient, as SQ SCIT requires many visits to the clinician and thereby lost productivity at work.

Previously, a sublingually administered immunotherapy (SLIT)-tablet has been introduced for the treatment of grass pollen AR. Recently, a similar SLIT-tablet, the SQ SLIT-tablet (ACARIZAX), has been developed for the treatment of HDM AA and AR. With a clinical development program including eight completed trials with more than 5000 patients the efficacy and a favorable safety profile of SQ SLIT-tablet have been demonstrated^4–11. On the contrary to the treatment course of SQ SCIT, the treatment course of SQ SLIT-tablet ensures convenience for the patient and a minor burden on the healthcare system and society as the tablet can be self-administered at home, except for the very first tablet.

Currently no head-to-head comparison of HDM SLIT-tablets and HDM SCIT products are available and, therefore, there is no direct way of comparing the efficacy of the SQ SLIT-tablet and SCIT for HDM RAD. When head-to-head trials are not available, indirect comparisons can be used based on meta-analysis. However, due to inter-study heterogeneity in HDM SCIT studies, a meta-analysis comparing the efficacy of SQ SLIT-tablets and HDM SCIT products will contain evidence which can be considered weak^12,13. A feasible approach would be to compare HDM AIT studies with a similar study design, selection criteria and scoring of patient reported outcomes. Comparisons of outcomes for trials with similar design features may be made, as seen in a study by Mosbech et al.¹, where a HDM SLIT-tablet trial is compared to two HDM SCIT trials with similar selection criteria^14,15. Based on similarities in the trial designs, patient population and selection criteria in general, Mosbech et al.¹ state a comparable effect and no significant difference between the HDM SLIT-tablet and SCIT trials. Based on this approach there would be no reason to believe that the efficacy of SQ SLIT-tablets is different from the efficacy of SQ SCIT.

A cost-minimization analysis was the chosen method for this analysis, based on the assumption of similar efficacy between HDM SLIT-tablet and HDM SCIT, with the purpose of comparison of the economic consequences of treating an average patient with HDM RAD using either SQ SLIT-tablet or SQ SLIT.

Methods

Cost-minimization analysis

A cost-minimization analysis is relevant when the two healthcare technologies in comparison are equivalent in terms of efficacy¹⁶. The analysis was performed according to health economic guidelines^16,17 as a model-based analysis developed in Microsoft Excel 2013 comparing costs related to the healthcare sector and society, as well as costs of administration for the patients including productivity losses¹⁶. Therefore, the treatment costs and costs related to administration of SQ SLIT-tablet (Dermatophagoides pteronyssinus (D. pteronyssinus) and Dermatophagoides farinae (D. farinae), 12 SQ-HDM, ALK, Denmark) were compared with the treatment costs and costs of administration of SQ SCIT (Alutard SQ, D. pteronyssinus, 100 000 SQ-U, ALK, Denmark).

Course of treatment and resource use

The SQ SLIT-tablet consists of components from the two predominant species of HDMs; D. pteronyssinus and D. farinae. To obtain the same treatment with SQ SCIT this would require two types of SQ SCIT treatments, as SQ SCIT is specific AIT treating one allergen per treatment. In Denmark, however, patients are very rarely treated for more than one HDM species¹⁸, and the focus was, therefore, assumed to be on the costs of treatments for patients suffering for one HDM allergy only¹⁸.

The courses of treatment differ between SQ SLIT-tablet and SQ SCIT. During the 3-year treatment with SQ SLIT-tablet, there are two initial consultations and a follow-up consultation the first year of treatment followed by two follow-up consultations every year during the remaining years of treatment¹⁸. As the patient must take the SQ SLIT-tablet every day, the number of tablets consumed through the course of a SQ SLIT-tablet treatment was calculated as the daily dose of one tablet times the average number of days per year and the compliance rate.

The injections associated with SQ SCIT are given at consultations. According to guidelines and Summary of Product Characteristics (SmPC), the 3–5-year treatment with SQ SCIT consists of an up-dosing period and a maintenance period. The up-dosing period involves a series of 15 up-dosing injections with 1-week intervals on average followed by two transition injections with 3-week intervals on average. For the maintenance period, injections are given with 8-week intervals on average. Approximately 80% of the patients are treated for 3 years, and ∼20% of the patients are treated for 5 years¹⁸. A titration kit contains the vials necessary for up-dosing. The number of maintenance vials was calculated based on the number of maintenance visits, which were determined by the remaining number of weeks per year after the up-dosing phase and the average interval between maintenance visits.

Table 1 presents an overview of the general assumptions used in the cost estimations, including assumptions on treatment duration and level of compliance.

Table 1. General model assumptions.

Assumptions	Details
General
Discount rate	According to Danish guidelines, the discount rate is 3%^14^,^15.
Patient costs	Patient costs include travel cost (10 km per visit) and lost wages (2 h per visit).**
	SQ SLIT-tablet	SQ SCIT
Duration of treatment	All patients are treated for 3 years.*	80% of the patients are treated for 3 years and 20% of the patients are treated for 5 years.*
Immunotherapy treatment and visits	Year 1: treatment is initiated by two consultations, i.e., the administration of first tablet in the clinic, and investigation of desired treatment effect ∼1 month later. Initial consultations are followed by an additional follow-up consultation. Years 2 and 3: two follow-up consultations per year^16.	Treatment is initiated with 15 weekly consultations. This is followed by a transition phase with one consultation 2 weeks after the last up-titration consultation and an additional consultation 4 weeks after the first transition consultation. After the transition phase, maintenance consultations occur with 8-week intervals^16.
Treatment setting	25% of the initial visits are carried out by a general practitioner, 10% are carried out by a medical specialist in a hospital on an outpatient basis, and 65% are carried out by a medical specialist in a private clinic (specialists in internal medicine: 50%, specialists in otolaryngology: 50%). The distribution of follow-up visits are 40% at general practitioners, 5% by a medical specialist in a hospital on an outpatient basis, and 55% by a medical specialist in a private clinic^16.	20% of the up-dosing visits are carried out by a general practitioner, 60% are carried out by a medical specialist in a private clinic, and 20% are carried out by a medical specialist in a hospital on an outpatient basis; 20% of the maintenance visits are carried out at a general practitioner, 60% are carried out by a medical specialist in a private clinic, and 20% are carried out by a medical specialist in a hospital on an outpatient basis^16.
Additional medical supervision	No peak flow measurements are carried out.*	Peak flow measurements are carried out before and after each injection.*
Compliance	Compliance is 80%.*	Compliance is 100% in the up-dosing phase and 90% in the maintenance phase.*
Tablets/Vials	The purchase of tablets is calculated according to the best fit of the remaining treatment resulting in as little waste as possible of the last package.	Vials are personal. A maintenance vial contains 5 mL and 4.7 injections can be extracted from each vial. Any remaining liquids in the titration kit after the up-dosing injections are used in the maintenance phase.*
Treatment of second allergy	Patients who are treated for both HDM- and grass allergy have an additional start-up visit.	50% of physicians treating patients for two allergies treat for both allergies at the same consultation. The remaining 50% initiate the treatment of the second allergy after the up-dosing phase of the first treatment. When injections are given at the same consultation the second injections are given 30 minutes after the first.*

*The compliance rates are based on assumptions.

**10 km per visit and 2 h per visit based on experiences on daily practice in Denmark.

Consultations in relation to both SQ SLIT-tablets and SQ SCIT are carried out by general practitioners, specialists in internal medicine, allergology and otolaryngology (allergological services) in both private clinics and in hospitals on an outpatient basis¹⁸. The average resource use associated with SQ SLIT-tablet and SQ SCIT treatments appear in Table 2 and the applied unit cost estimates appear in Table 3.

Table 2. Average resource use for treatment of a patient with HDM RAD.

Resource category	Resource type	Year 1	Year 2	Year 3	Year 4	Year 5
SQ SLIT-tablet
Medication	Number of tablets^a	292	292	292	—	—
Physician	Number of initial visits^b	2	—	—	—	—
	Treatment by general practitioner (visits)	0.50	—	—	—	—
	Treatment by medical specialist (visits)	1.30	—	—	—	—
	Treatment in hospital (visits)	0.20	—	—	—	—
	Number of follow-up visits^c	1	2	2	—	—
	Treatment by general practitioner (visits)	0.40	0.80	0.80	—	—
	Treatment by medical specialist (visits)	0.55	1.10	1.10	—	—
	Treatment in hospital (visits)	0.05	0.10	0.10	—	—
Patient	Total time spent (hours)^d	6	4	4	—	—
	Travel distance (km)^e	30	20	20	—	—
SQ SCIT
Medication	Number of up-titration kits	1	—	—	—	—
	Number of maintenance vials needed^f	1	2	1	1	—
Physician	Up-titration injections (visits)	15	—	—	—	—
	Treatment by general practitioner (visits)	0.8	—	—	—	—
	Treatment by medical specialist (visits)	11.3	—	—	—	—
	Treatment in hospital (visits)	3.0	—	—	—	—
	Maintenance injections (visits)	5.4	5.9	5.9	5.9	2.2
	Treatment by general practitioner (visits)	1.1	1.2	1.2	1.2	0.4
	Treatment by medical specialist (visits)	3.2	3.5	3.5	3.5	1.3
	Treatment in hospital (visits)	1.1	1.2	1.2	1.2	0.4
	Number of peak flow measurements	40.8	11.7	11.7	11.7	4.3
Patient	Total time spent (hours)^d	40.8	11.7	11.7	11.7	4.3
	Travel distance (km)^e	204.0	58.5	58.5	58.5	21.5

a One tablet/day; compliance = 80%;

b two initial visits;

c One follow-up visit 1^st year; 2 follow-up visits the following years;

d 2 h/visit based on experiences on daily practice in Denmark;

e 10 km/visit based on experiences from daily practice in Denmark;

f number of maintenance visits (injections)/number of injections per maintenance vial; i.e., number of maintenance visits (injections)/4.7; Remaining injections in opened vial at the end of the year are used in the following year.

Table 3. Unit costs (€).

Cost category	Cost type	Unit	€/unit	Source
Medication
SQ SLIT-tablet	Pack with 30 tablets	Pack	97.8	www.medicinpriser.dk^19
	Pack with 90 tablets	Tablet	286.4	www.medicinpriser.dk^19
SQ SCIT	Titration kit, Mite	Titration kit	265.7	www.medicinpriser.dk^19
	Maintenance vial, Mite	Vial (5 mL)	230.7	www.medicinpriser.dk^19
Physician visits
General practitioners	Visit	Visit	18.3	www.laeger.dk^20
	Peak flow measurement	Measurement	5.1	www.laeger.dk^20
Medical specialist,	First visit	Visit	82.9	www.laeger.dk^20
Internal medicine	Second visit	Visit	59.1	www.laeger.dk^20
	Subsequent visit	Visit	19.5	www.laeger.dk^20
	Allergy injection – 1^st allergen	Injection	41.4	www.laeger.dk^20
	Allergy injection – subsequent allergen	Injection	16.6	www.laeger.dk^20
	Lung functions test	Test	82.8	www.laeger.dk^20
Medical specialist,	First visit	Visit	81.8	www.laeger.dk^20
Otorhinolaryngologist	Second visit	Visit	45.0	www.laeger.dk^20
	Subsequent visit	Visit	21.9	www.laeger.dk^20
	Allergy injection – 1^st allergen	Injection	0.0	www.laeger.dk^20
	Allergy injection – subsequent allergen	Injection	0.0	www.laeger.dk^20
	Peak flow measurement	Measurement	0.0	www.laeger.dk^20
	Lung functions test	Test	0.0	www.laeger.dk^20
Hospital	Outpatient visit	Visit	102.8	www.drg.dk^21
	Additional costs, uncomplicated allergy treatment	Visit	128.9	www.drg.dk^21
Patient costs
Work	Productivity loss/foregone earnings^a	Hour	41.7	www.statistikbanken.dk^22
Travel	Travel by private car	Km	0.5	www.skat.dk^23

2015-price level.

a Productivity loss/foregone earnings are based on the mean salary/hours for the general population aged 18–65 years in Denmark, including the unemployed.

Data about resource use in terms of medication use, physician visits, and patient time were based on information from clinical trials and treatment guidelines in Denmark (according to the SmPC); where information was limited, medical expert opinion was acquired¹⁸. The clinical experts represented all relevant medical specialties, ensuring a representative and robust description of Danish clinical practice.

Unit costs

Market prices were applied as unit cost estimates for medication¹⁹. The fees for consultations and treatments at general practitioners and specialists in private clinics were obtained from the Danish Medical Association²⁰. The applied fees and charges included consumables. Charges for treatments in the hospital (outpatient charges) were obtained from the Danish Health Data Agency (Sundhedsdatastyrelsen)²¹. Average gross wages from Statistic Denmark were applied as cost estimates for hours of lost work²². Travel cost per kilometer was based on national rates for travel reimbursement in private vehicles²³.

Costs were obtained in Danish kroner (DKK) but converted into Euro (€) using the average exchange rate from 2015 (€1 = 7.46 DKK). Costs were reported in 2015 prices and future costs beyond the first year were discounted to present value (PV) with 3% according to Danish guidelines^24,25.

Sensitivity analyses

In order to test the robustness of the results, comprehensive univariate sensitivity analyses—changing different parameters one-by-one—were performed.

Results

Costs of treatment with SQ SLIT-tablet and SQ SCIT

Table 4 presents the results of the budget impact and cost-minimization analyses. For an average patient receiving AIT, the direct cost (present value) of treating HDM RAD with SQ SLIT-tablet is €3094, while the direct cost of a treatment with SQ SCIT is €3799. The total treatment cost for an average patient with HDM RAD is €3697 for treatment with SQ SLIT-tablet and €6717 for SQ SCIT. The difference is driven by both treatment costs and indirect costs. The cost of medication is lower for SQ SCIT; however, the larger amount of consultations more than outweigh this difference.

Table 4. Cost of treatments for HDM RAD with SQ SLIT-tablet and SQ SCIT (€).

Cost category	Cost type	Year 1	Year 2	Year 3	Year 4	Year 5	PV
SQ SLIT-tablet
Treatment costs	Medication	1146	1146	580	—	—	2804
	Physician start-up visits, total	143	—	—	—	—	143
	Treatment by GP	9	—	—	—	—	9
	Treatment in private clinic	87	—	—	—	—	87
	Treatment in hospital	46	—	—	—	—	46
	Physician follow-up visits, total	30	61	61	—	—	146
	Treatment by GP	7	15	15	—	—	35
	Treatment in private clinic	11	23	23	—	—	55
	Treatment in hospital	12	23	23	—	—	56
Total treatment costs		1319	1206	640	—	—	3094
Patient costs	Travel expenses	15	10	10	—	—	34
	Productivity loss/Foregone earnings	250	167	167	—	—	570
Total costs		1584	1383	817	—	—	3697
SQ SCIT
Treatment costs	Medication (titration kits)	266	—	—	—	—	266
	Medication (vials)	231	461	231	46	—	938
	Physician up-dosing injections, total	1209	—	—	—	—	1209
	Treatment by GP	86	—	—	—	—	86
	Treatment in private clinic	429	—	—	—	—	429
	Treatment in hospital	695	—	—	—	—	695
	Physician maintenance visits, total	415	450	450	90	30	1385
	Treatment by GP	31	33	33	7	2	103
	Treatment in private clinic	134	145	145	29	10	448
	Treatment in hospital	250	271	271	54	18	835
Total treatment costs		2121	911	681	136	30	3799
Patient costs	Travel expenses	101	29	29	6	2	164
	Productivity loss/Foregone earnings	1703	488	488	98	32	2755
Total costs		3925	1429	1198	240	71	6717

2015-price level. PV, present value (future costs beyond the first year discounted to present value).

Figure 1 shows how the potential for saved direct treatment costs (black bars) depends on the number of patients treated with SQ SCIT. The figure also shows how the potential for treating more patients at the same cost (brown bars) depends on the number of patients treated with SQ SCIT. If, for example, 2500 patients are treated with SQ SLIT-tablet instead of SQ SCIT, the potential for reduced direct treatment costs amounts to ∼€1.8 million. The reduction corresponds to the cost of treating ∼600 additional patients with the SQ SLIT-tablet, i.e., 24% more patients.

Figure 1. Relationship between number of patients treated, potential treatment cost savings and potential additional patients treated, HDM RAD. PV, present value.

Sensitivity analyses

The results of a series of univariate sensitivity analyses appear from Table 5. Only direct costs were included in the sensitivity analyses. Input parameters affecting the cost of treatment for both SQ SLIT-tablet and SQ SCIT were changed.

Table 5. Univariate sensitivity analysis for HDM RAD (direct treatment costs in €).

Sensitivity analyses	Direct treatment costs (€) for SQ SLIT tablet, PV	Direct treatment costs (€) for SQ SCIT, PV	Difference from SQ SLIT tablet, PV
General
Base case	3094	3799	+705
Discount rate
1%	3141	3851	+711
5%	3048	3749	+700
SQ SLIT-tablet
Initiation of treatment
100% hospital setting	3414	3799	+384
100% general practice	2987	3799	+811
100% medical specialists	3085	3799	+713
Follow-up treatment
100% hospital setting	4066	3799	−267
100% general practice	3036	3799	+763
100% medical specialists	3047	3799	+751
Number of visits per year
4 + 3+3	3182	3799	+617
2 + 1+1	3005	3799	+793
Compliance
100%	3744	3799	+55
60%	2345	3799	+1454
SCIT
Injections per vial
4.5	3094	3880	+787
4.9	3084	3807	+713
Up-titration visits
100% hospital setting	3094	6065	+2971
100% general practice	3089	3017	−76
100% medical specialists	3089	3304	+210
Maintenance visits
100% hospital setting	3094	6586	+3493
100% general practice	3094	2928	−166
100% medical specialists	3094	3160	+66
Number of weeks between injections
10 weeks	3094	3313	+220
6 weeks	3094	4473	+1380
Compliance, up-titration
80%	3094	3568	+474
Compliance, maintenance
100%	3094	4024	+931
60%	3094	3136	−42
Duration of treatment
100% treated for 3 years, 0% for 5 years	3094	3648	+554
60% treated for 3 years, 40% for 5 years	3094	2491	−560

2015-price level. PV, present value.

With a few exceptions, the sensitivity analyses showed that the cost of treatment for HDM RAD with SQ SLIT-tablet was lower than the cost of treatment with SQ SCIT, regardless of which parameter was changed. Due to the large number of physician visits associated with the treatment with SQ SCIT, parameters affecting the treatment setting had a relatively large impact on the SQ SCIT treatment costs.

Discussion

In this cost-minimization analysis, the economic impact of treatments with SQ SLIT-tablet vs SQ SCIT was analysed. Equal efficacy of SQ SLIT-tablet and SQ SCIT was assumed.

When including only direct costs of the treatments, the treatment costs for an average patient with HDM RAD was estimated to a potential savings of €705 for the SQ SLIT-tablet compared to SQ SCIT. The robustness of these results was confirmed by the sensitivity analyses, showing that the SQ SLIT-tablets, with a few exceptions, were cost saving. However, some of the performed sensitivity analyses must be characterized as analysis of extremes—e.g., a 100% follow-up in a hospital setting for SQ SLIT-tablet treatment is not realistic.

The difference in treatment costs between SQ SLIT-tablet and SQ SCIT implies that there is a potential for reducing the costs of treatment for HDM RAD if patients are treated with the SQ SLIT-tablet instead. Alternatively, there is a large potential for increasing the number of treated patients at unchanged costs.

As stated, allergy is associated with substantial cost to society, implying that information about the costs of a SQ SLIT-tablet vs SQ SCIT is highly relevant. The findings of this analysis is supported by a recently published review²⁶ in which it is reported that therapy with SLIT-tablets is associated with lower costs compared to SCIT in four out of six studies. In addition, it is also reported that SLIT-tablets and SCIT are cost saving compared to pharmacotherapy, which only provides short-term symptomatic relief.

The main driver of the cost difference between treatments with SQ SCIT and SQ SLIT-tablet in this analysis was the difference in the number of physician visits throughout the respective treatment periods. In addition, it should be noted that the treatment with SQ SLIT-tablet is a more convenient form of treatment for patients, as the number of physician visits will be reduced markedly. However, home administration may influence the compliance rate. In the analysis the compliance rate for SQ SLIT-tablet was set to 80%, which was lower than the compliance rate for SQ SCIT. Nevertheless, it should be noted that a Swedish study found compliance rates for SLIT-tablets to be high and on the same level as compliance rates for SCIT²⁷.

This analysis had some limitations. First, the perspective of the analysis was relatively restricted as only the treatment costs, costs of administration and patients’ costs related to the administration were included. That is, this analysis does not provide a full picture of the costs of HDM RAD.

Second, costs associated with treatment of adverse events related to SQ SCIT and SQ SLIT-tablet, respectively, were not included, assuming costs related to adverse events of both treatment modalities were equal. Some studies²⁸ indicate that the number of adverse events may be lower in SLIT-tablet therapy compared to SCIT, implying that exclusion of the costs of adverse events lead to a more conservative estimate of the saved costs associated with SQ SLIT-tablet therapy.

Third, fees and charges were applied as unit cost estimates. These may not accurately reflect the opportunity cost, which should ideally be used in such analyses. However, the fees and charges used were considered the best available proxies for the opportunity costs.

Finally, data/assumptions on treatment setting (patient distribution) and compliance were based on advice from experts, implying some degree of uncertainty for these parameters.

Conclusion

In conclusion, this cost-minimization analysis showed that treatment with SQ SLIT-tablet is a cost-saving alternative to SQ SCIT when treating patients with persistent moderate-to-severe HDM AR, despite use of symptom-relieving medication. From a healthcare perspective, the SLIT-tablet represents an efficient use of cost and resources. Further analyses may be necessary to evaluate the overall health economic consequences of implementation of the SQ SLIT-tablet instead of SQ SCIT.

Transparency

Declaration of funding

This study was supported by ALK.

Declaration of financial/other relationships

SR, CRJ, ST, and AW have received advisor/consultants fees from ALK. Incentive has received consultancy fees from ALK. JO is an employee of Incentive. JHP and JNA are employees of ALK.

Notice of correction

Please note that tables 4 and 5 have been corrected since the article was first published online (15 March 2016).