It was also assumed that BCVA switch cut-offs of 7

It was also assumed that BCVA switch cut-offs of 7.5 and 22.5 letters would correspond to transitions of one and two health states respectively (Table?3). Table 3 Mapping of the probabilities for the parametric estimation Adverse events, Standard error MortalityAt any time and health state, patients could move to the PT-2385 death health state. The progression to the Death state was estimated using the mortality rates of the general population, using the Italian mortality tables (year 2018), specific for sex and age (source: ISTAT [18]), and adjusted by the additional risk of any VA-related mortality [19]. Utility inputs In the model, each visual acuity state was associated with one utility score (Table ?(Table5).5). of central vision, visual distortion, and an impaired capacity of perceiving colour contrast and PT-2385 intensity. Brolucizumab, a new generation anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody, was approved by the European Medicines Agency for the treatment of nAMD. The aim of this analysis is to evaluate the cost-effectiveness profile of brolucizumab, compared to the main therapeutic alternative available (aflibercept), for the treatment of nAMD. Methods The simulation of costs and outcomes was carried out using a Markov model over a time horizon of 15?years. In base-case, treatment effectiveness inputs for brolucizumab and aflibercept were extracted from your HAWK and HARRIER studies and from a network meta-analysis. The Italian National Healthcare Support (NHS) perspective was considered, therefore only healthcare direct costs (treatment acquisition, administration, adverse events, disease monitoring) were analysed. In the alternative scenarios, the societal perspective and a prolonged time horizon were considered. Model robustness was tested through sensitivity analyses. Results In the base-case analysis, brolucizumab was dominant over aflibercept (+?0.11?years QALY gained and -15,679 costs). Both one-way deterministic and probabilistic sensitivity analyses confirmed the robustness and reliability of base-case results. The results of the probabilistic sensitivity analysis showed that when the willingness to pay is usually equal to 50,000 per QALY gained, brolucizumab would be dominant in 84% of simulations and in the remaining simulations brolucizumab would be cost-effective compared to aflibercept. Results of the alternative scenarios and sensitivity analyses confirmed the results of base-case. Conclusion The cost-utility analysis shows that brolucizumab is dominant over aflibercept. Treatment with brolucizumab reduces the economic impact of nAMD and decided a slight increase of quality-adjusted survival. This analysis gives a high level of confidence that the treatment with brolucizumab would reduce the burden of intravitreal injections, compared to aflibercept, a relevant therapeutic alternate in Italy. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-022-07972-w. Best Corrected Visual Acuity At baseline, in the HAWK & HARRIER studies (pooled analysis), 27.14% of patients experienced bilateral disease (Best Corrected Visual Acuity, Standard deviation Table ?Table22 shows the efficacy results (BCVA change from baseline) in the brolucizumab and aflibercept arms, regardless of baseline BCVA. Since total PT-2385 datapoints to simulate 12 months 2 were not available, clinical efficacy observed during the first 44?weeks of 12 months 2 (weeks 53C96) in the HAWK and HARRIER trials [10, 13, 14], intended as BCVA gain or loss (compared to BCVA at week 52), was scaled back to 52?weeks. To adjust 44-week trial data in 12 months 2 (96?weeks together) to the full year (i.e. 52?weeks), it was assumed that Lum this VA gain/loss would continue progress at the same rate for the remaining 8?weeks. Transition probabilities The transition matrices between health states of the Markov model were calculated using the BCVA switch (observed with brolucizumab and aflibercept in HAWK and HARRIER studies [10, 13, 14]), expressed as the number of letters gained or lost compared to baseline, by transforming these parametric data into transition probabilities. Transitioning is only possible up to two health says up or down in any given model cycle. To estimate the probability of gaining or losing a number of letters, the switch in BCVA was assumed to follow a normal distribution with the estimated mean and SD, accordingly to the approach proposed by Hodgson et al. 2017 [17]. Using the normal cumulative density function, it is possible to estimate, given the imply and VA letter change cut-offs, the probability of moving across these cut-offs. It was also assumed that BCVA switch cut-offs of 7.5 and 22.5 letters would correspond to transitions of one and two health states respectively (Table?3). Table 3 Mapping of the probabilities for the parametric estimation Adverse events, Standard error MortalityAt any time and health state, patients could move to the death health state. The progression to the Death state was estimated using the mortality rates of the general populace, using the.