This study estimated the cost-effectiveness ratio of the 5-grass pollen tablet treatment by comparison of the 5-grass pollen tablets treatment with placebo treatment based on a decision tree populated with hypothetical data. This assessment produced results that can be considered favourable from a sustainability point of view. The cost-effectiveness ratio acceptability curve based on the multivariate probabilistic sensitivity analysis shows that the cost-effectiveness ratio remains below the ‘critical’ threshold of € 30,000/QALY in nearly all scenarios simulated. This study has several strengths that contribute to the robustness of these findings. First, the effectiveness data that were used to constitute the structure of the model were taken from a double-blind randomised controlled trial [
12,
13]. Second, the use of the AAdSS as an effectiveness indicator permitted identification of a direct relationship between the outcome and the decrease in the consumption of resources (e.g. corticosteroids, diagnostic testing, etc.), which in part offsets the cost of 5-grass pollen tablets and thus makes a decisive contribution to the sustainability of NHS resources. Nevertheless, this study also faced several limitations. Although it used data derived from randomised controlled clinical trials, the model fits hypothetical scenarios. However, previous model-based studies of economic evaluation of AIT have provided significant findings in the understanding of the cost effectiveness of this treatment [
10,
21]. Despite being estimated on the basis of the existence of a direct relationship between symptoms and the consumption of resources, the reliability of the cost-related part could be significantly improved if it were based on the resources actually consumed by patients using the microcosting method. Similarly, the utility coefficients, which were extrapolated using the ROC curve, could be measured directly by administering a questionnaire, such as the Euroqol (EQ 5D) [
22], to AR patients. In fact, the EQ5D appears to be particularly appropriate for assessing AR, as severe or moderate AR may be presumed to have an impact on the patient’s ability to perform everyday activities (e.g. sport, work, etc.) and his/her psychological condition. It is also true that the multivariate probabilistic sensitivity analysis conducted on the deterministic results of the study gives a sufficient safety margin as to the sustainability of the cost-effectiveness ratio, which would presumably remain below the threshold of € 30,000/QALY in any case, even if the model was populated with real data and different discount rates (varied between 1.5 and 5 % in the sensitivity analysis) were used. In particular, the discount rate potentially appears be one of the most sensitive parameters as the time horizon is limited to 4 years. In this sense, this study provides added value with respect to the previous economic assessments of the use of SLIT vaccines to treat AR [
8‐
11]. Of note, the finding that the cost effectiveness of 5-grass pollen tablet treatment increases with the severity of AR symptoms agrees with the findings of a recent report regarding the higher clinical efficacy of the 5-grass pollen tablet treatment in patients with more severe AR [
23]. In this analysis, the study centres were grouped into tertiles (low, middle, and high tertiles) according to the symptom severity scores observed in the placebo patients at each centre to assess the difference in the average score between the treatment and placebo groups in each tertile. The results indicated an increased treatment effect in the most severe patients, independent of the symptom score used, during pollen season. Of note, a recent study showed that the 5-grass pollen tablet is more cost-effective than the tablet containing only one grass, i.e.
Phleum pratense [
24]. This could be related to the fact that a 5-grass pollen preparation fits better with patient’s sensitisation profile, as shown by laboratory studies [
25] and botanical observations [
26], and thus may result in higher clinical effectiveness.
Lastly, attention should be drawn to the need to examine the administration of SLIT from an organisational point of view. The results of the clinical trials [
12,
13] used in the model show that the treatment is, in all cases, effective only when at a compliance rate of 75 % or greater. However, sensitivity analysis showed that increased levels of compliance result in an increase of the ICER which, anyway, remains under the € 30,000/QALY threshold even though a 100 % compliance is assumed. This percentage is clearly of fundamental importance for the NHS when considering the level of investment that will be remunerative in terms of health gains. Thus, awareness that treatment effectiveness depends on a high level of patient compliance and adherence, which could be achieved with adequate education both at the specialist allergy centres [
27] and by general practitioners when providing SLIT, must be a primary consideration.