Diabetic macular oedema (DME) is the leading cause of vision loss in diabetic retinopathy and, consequently, of blindness in patients with diabetes mellitus1. As such, it has a strong negative impact on patients.

This inflammatory disorder is a consequence of metabolic changes secondary to hyperglycaemia caused by diabetic retinopathy in the macula. Vasogenic changes that induce rupture of the blood-retinal barrier together with inflammatory activation lead to severe retinal damage and chronic macular changes2.

The clinical objectives of the treatment of DME are to reduce the severity of oedema and prevent loss of vision3. Treatment is based on effective metabolic control (glycaemia, hypertension, lipid profile, renal function), but requires further measures to prevent vision loss, such as laser photocoagulation and drug treatments4. Approved treatments for DME include two groups of medications which are delivered by intravitreal injection: vascular endothelial growth factor inhibitors (anti-VEGF), such as ranibizumab and aflibercept, and corticosteroids, such as dexamethasone in a sterile sustained-release implant. Posology is variable because the response to treatment over time determines the frequency of injections. Several clinical trials have found that these therapies are effective5–7. They are indicated for patients with DME, regardless of the recommendations or protocols that establish specific treatment algorithms.

Blindness, diabetic retinopathy, and DME are very frequent in diabetic patients. Blindness, diabetic retinopathy, and DME have prevalences of between 4% and 11%, of 40%, and between 1.4% and 7.9%, respectively8. DME and loss of visual acuity negatively affect patients’ health-related quality of life and affects their ability to perform everyday tasks, including the self-management of diabetes9,10.

DME and diabetic retinopathy have a high economic impact because of their direct costs as well as their indirect costs, such as reduced income or an increased need for social support as vision worsens11. It has been estimated that the annual resource utilisation and direct health cost per patient with DME are approximately double those of patients without DME12. Bilateral DME is associated with higher direct health costs and with higher indirect costs caused by its impact on working life13.

The aim of this study was to determine the budget impact on the Spanish National Health System of the inclusion of dexamethasone intravitreal implant (IVI) in the treatment of DME in a specific healthcare region in Spain.

The budget impact analysis was developed based on national and international recommendations14,15. The analysis was conducted using Microsoft Excel. An expert panel comprising three vitreoretinal specialists was consulted to validate the values of the parameters obtained from the literature and to reach a consensus on resource utilisation in standard clinical practice. This study assessed the incremental budget impact of the inclusion of dexamethasone IVI as a new therapeutic alternative for DME.

After applying epidemiological data for DME in Spain to a healthcare region with 25,000 adult inhabitants, we estimated that 100, 112, and 124 patients would be eligible for treatment per year over the 3-year study period.

In the scenario without dexamethasone IVI, the total annual cost of treating DME in these patients would be €835,197 (year 1), €606,004 (year 2), and €555,227 (year 3). In the scenario with dexamethasone IVI, the total annual costs would be €800,167 (year 1), €595,262 (year 2), and €550,176 (year 3). Thus, the inclusion of this treatment modality in the therapeutic arsenal for DME would produce budget savings of 4.2% (year 1), 1.8% (year 2), and 0.9% (year 3) involving reductions of €35,030, €10,743, and €5,051, respectively (Table 4). The annual cost of treatment per patient would be reduced by €350.31 (year 1), €95.97 (year 2), and €40.80 (year 3).

Relative to the scenario without dexamethasone IVI, the scenario with dexamethasone IVI would have led to an overall saving of 5% in drug costs over the 3-year study period (0.2%, 8%, and 9.5% per year, respectively). Drug delivery and monitoring costs would provide the greatest savings in total costs. Drug administration costs and monitoring costs would have been between 13% and 23.5% lower and between 2.5% and 4.6% lower, respectively. In the scenario with dexamethasone IVI, for the whole analysis period, drug delivery costs and monitoring costs would have been 17.01% and 3.93% lower, respectively.

Sensitivity analyses showed that an increase in the use of dexamethasone IVI would further reduce the annual costs relative to the scenario without the implant. The sensitivity analysis also showed that an increase in unitary costs of healthcare resources (excluding drug costs) would increase the total cost in the scenario without dexamethasone (drug delivery and follow-up) which is already the scenario with greater costs. Thus, this would increase the savings between scenarios due to the introduction of dexamethasone IVI. However, several factors could reduce the potential savings derived from the introduction of dexamethasone IVI. These factors include: reductions in the unitary costs of healthcare resources, not considering the cost of managing adverse systemic events, a decrease in the incidence of cataracts in antiangiogenic therapies, and increasing the number of dexamethasone IVI injections per year (Table 4).

For each of the 3-year analysis period, the total cost in a population of 100,000 adults (400 prevalent patients) would be €3.3 million, €2.4 million, and €2.2 million in the scenario without dexamethasone IVI and €3.2 million, €2.4 million, and €2.2 million in the scenario with dexamethasone IVI, respectively. In a medium-sized health area with a population of 250,000 adults (1,000 prevalent patients), for each of the 3 years the total cost of treatment for DME would be €8.4 million, €6.1 million, and €5.6 million in the scenario without dexamethasone IVI. The scenario with dexamethasone IVI would led to savings of €350,300, €107,426, and €50,511 in each year, respectively. In an area with a population of 500,000 adults, the total cost of treating DME without dexamethasone IVI would be €16.7 million, €12.1 million, and €11.1 million euros for each of the 3 years in study, respectively. The introduction of dexamethasone IVI would led to savings of €700,601, €214,852, and €101,022, respectively.

Diabetes mellitus is a highly prevalent disease and its prevalence is expected to increase over the coming years. Poor glycaemic control and subsequent complications, such as diabetic retinopathy and DME, are a great economic burden for the Spanish National Health System due to the challenge of managing this increasing number of patients.

According to recent economic data on DME in Spain, the estimated direct annual cost per patient with DME was €6,271 (excluding drug costs)13, whereas the estimated annual cost of treatment with antiangiogenic drugs was €7,154 with follow-up costs of €47423. DME can cause partial vision loss or blindness, which would entail an additional increase in indirect costs due to disability. The mean annual cost per patient due to permanent disability is €7,051, which is especially relevant in patients with bilateral DME (€11,712 in bilateral DME vs €4,284 in unilateral DME)13. A report on blindness in Spain24 has suggested that the cost is around €5,100 per blind patient per year, entailing a total cost of around €360 million. There are additional costs that are paid by blind patients (€25,914) or those with impaired vision (€11,032)25. Besides good glycaemic control, opting for more effective treatments would reduce the economic burden on the Spanish National Health System service of treating patients with DME.

According to the model, the inclusion of dexamethasone IVI in the therapeutic arsenal for DME would save €35,030, €10,743, and €5,051 over each of the 3 years of analysis, respectively. These savings would mainly be due to the lower rate of treatments with dexamethasone IVI, which would in turn reduce drug delivery and follow-up costs. Annual savings per patient would be between €41 and €350. These estimations are corroborated by the alternative scenario in which there is increased use of dexamethasone IVI, suggesting that there would be even greater savings over the study period.

To the best of our knowledge, this study is the first to assess the impact on the healthcare budget of currently available treatments for DME in Spain, including dexamethasone IVI. A review of the literature found three recent economic assessment studies conducted in different countries that analysed the efficiency of several anti-VEGF therapies26–28. However, we found only two studies that included dexamethasone IVI25,29. One of these was a cost-effectiveness analysis conducted in Spain, which suggested that dexamethasone IVI was an efficient option with a cost of €2,050 per line of visual acuity gained25.

The present study has some limitations. The main limitation is related to the estimation of the target population. The robustness of the data is affected by the reliability of the epidemiological data available for DME, because the studies from which the data were obtained were conducted with relatively small reference populations17,18. The percentages of usage of the different therapeutic alternatives represent possible future trends in the usage of these drugs. The results obtained could vary if the estimated values of medication use do not closely reflect changes in the market.

The lack of robust information on the real-world management of patients with DME meant that some parameters had to be provided by the expert panel. Therefore, the following estimates may not accurately represent daily clinical practice in all Spanish healthcare centres: the number of intravitreal injections, the number of annual visits needed to treat patients with the therapeutic alternatives, resource utilisation caused by adverse events and patient follow-up.

Complete economic assessments, such as cost-effectiveness or cost-utility analyses, allow us to determine the comparative efficiency of the available alternatives for the treatment of a given disease. Budget impact analyses, such as that conducted in this study, involve partial economic assessments which analyse the economic impact of different therapies without assessing their effectiveness or efficacy, thus making them complementary to other assessments. This type of assessment should be seen as a useful tool for decision-making in healthcare, particularly in settings in which healthcare budget control is a priority. However, future studies should help to complement the information presented in this study and therefore assist in this decision-making process.

In conclusion, the use of dexamethasone IVI for the treatment of DME would entail savings to healthcare budgets. These savings would mainly be due to the reduced costs of drug delivery and patient follow-up.

The project was conducted with unconditional funding from Allergan, SAU.

Fernando de Andrés and Itziar Oyagüez work at PORIB, a consultancy specializing in economic assessments of health technologies that received funds from Allergan SAU to conduct this project. Enrique Cervera, Luis Arias and Félix Armadá received honoraria from Allergan SAU for this project as consultants to Allergan SAU. Concha Martínez works at Pricing and Market Access, Allergan SAU. The authors declare that this financial support does not represent a conflict of interest in relation to the development of this article.

This article was partially presented as a brief report at the 19th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), held in Vienna (Austria), from October 29, 2016 to November 2, 2016.

The authors declare that this work has not been published nor is it in the process of being considered for publication in any other journal.