Pricing for Multi-Indication Drugs in the Italian Regulatory Context.

Background: The authorization of new therapeutic indications for drugs already reimbursed by the Italian National Health Service (NHS) represents a matter of importance. This study aims to estimate the additional discount attributed to the extension of indications (EoIs) to explore the potential correlation between spending and negotiated discounts and to find specific factors (determinants) that impact on discount.

Methods: The study focused on drugs approved in Italy between 2003 and 2017 with at least four therapeutic indications, including the first approved and EoIs, with follow-up extended until 2021 to acquire all the information on the negotiation process that has been completed. Data were obtained from reimbursement and pricing dossiers, and negotiation assessments. Trends in the number of EoIs submitted and the additional discounts negotiated were analyzed, along with the relationship between the negotiated discount and subsequent drug expenditure. Determinants influencing the extent of the negotiated discount were assessed, including drug type, orphan drug designation, innovativeness status, number of EoIs, disease incidence and prevalence, estimated number of patients, revenue projections, availability of therapeutic alternatives, and efficacy outcomes. A Wilcoxon nonparametric test was used to evaluate the associations between determinants and the negotiated additional discount, with a significance level of 0.05.

Results: The study identified nine medicines: five of these were used in onco-hematologic therapeutic areas, while the remaining four were immunosuppressants for dermatologic and/or rheumatologic conditions. These nine active substances accounted for 65 approved therapeutic indications, of which 50 were reimbursed by the Italian NHS, including the first indication; the analysis focused only on 40 reimbursed EoIs. The additional discount obtained for EoIs averages approximately 12.5% (95% CI 9.4-16.6%), with a median value of approximately 11%. This latter value was used as the threshold in the analysis of the determinants potentially impacting the negotiated discount amount. Discounts greater than 11% were significantly associated with EoI beyond the fifth and oncology drugs. The additional discount seemed small when compared with the increased spending.

Conclusion: AML seems to incur substantial direct economic expenses. Reducing the days of hospitalization can significantly decrease the economic burden of AML in the European Union. Moreover, there is a necessity for studies that comprehensively evaluate the economic implications, particularly concerning total and indirect costs.

Registration: The study provides valuable insights into the negotiation outcomes for medicines with multiple therapeutic indications, particularly in onco-hematologic and immunosuppressive areas. The analysis revealed that additional discounts for EoIs averaged 12.5%, with a median of 11%, a value used to assess the impact of specific determinants. A discount higher than 11% was statistically correlated with drugs having more than five indications and oncology treatments, showing their influence in negotiations. However, the savings from discounts were modest relative to the increased drug spending as more indications were approved. This suggests an imbalance between the cost control achieved through discounts and the rising expenditure due to expanded drug use.