The Health Technology Assessment (HTA) of medicines is performed separately at the country level with some differences, but Italy, France, and Germany have implemented price and reimbursement systems strongly focused on the Added Therapeutic Value (ATV). This study investigates the level of agreement on ATV assessments by Agenzia Italiana del Farmaco (AIFA), Haute Autorité de Santé (HAS), and Gemeinsamer Bundesausschuss (G-BA).

A database was created collecting all information about drugs with innovativeness status requests in Italy from July 2017 to December 2022 and populated with the corresponding HAS and G-BA ATV assessments. The primary comparative analysis was conducted by grouping the ATV ratings into “higher added value” and “lower or no added value”, while a secondary analysis considered the Italian innovativeness status as a criterion to include the quality of evidence assessment. The concordance between ATV assessments was investigated through percentage agreement and unweighted Cohen k-value.

189 medicines/indications were included. The greatest agreement was found when comparing G-BA versus HAS (82 percent; k = 0.61, substantial agreement). Lower levels of agreements were observed for AIFA versus HAS and AIFA versus G-BA (respectively 52 percent; k = 0.17 and 57 percent; k = 0.25). The secondary analysis led to a reconciliation to moderate agreement for AIFA versus HAS (72 percent; k = 0.45) and AIFA versus G-BA (74 percent; k = 0.47).

A high degree of concordance between HTA organizations is reached when considering jointly ATV and quality of evidence, suggesting that the system is extensively mature to make a Joint Clinical Assessment, avoiding duplications and reducing access inequalities.

An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.

Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.

To facilitate more structured MEA negotiations, we propose a conceptual “value-based negotiation framework” with corresponding application tools.

The framework was developed based on an iterative process of scientific literature review and expert input.

The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden.

The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products.

Health technology assessments (HTA) for combination drug therapies in oncology are increasingly common. Companies face multiple challenges when determining their economic value due to their complexity and high cost, while payers must balance the need for these vital innovations with sensitivity to rising costs. The study objective was to evaluate the current HTA frameworks in Europe and identify the potential barriers/solutions to reimbursement of brand-on-brand (BoB) combination therapy.

A targeted literature review of HTA agency websites was undertaken to identify any literature/guidance relating to HTA decision-making for combination oncology therapies in France, Germany, Sweden, and the UK.

In France and the UK, BoB HTA decisions reflect clinical- and cost-effectiveness. Combination therapies have been accepted for use in France and the UK, for example, dabrafenib plus trametinib, are assessed through standard HTA processes, exemplifying that positive reimbursement is not unattainable where there is an unmet need and high clinical value. Despite this flexibility, many therapies will fail to prove their cost-effectiveness, resulting in delays or arbitrary pricing decisions. Potential solutions are the use of the ‘efficiency frontier’, as typified by the German HTA system, giving more ‘scope‘ to expensive innovations; or the Swedish HTA approach, which applies variable cost-effectiveness thresholds according to therapeutic area, disease severity, and social criteria. Other possibilities include indication-specific pricing, multiple-criteria decision analysis, and net monetary benefit with willingness-to-trade weights. One likely issue to arise is when different companies are involved, necessitating co-operation. In this scenario, a simplistic solution would be arbitration of the division of the combined price, circumventing the need for HTA agencies to make changes to decision-making criteria.

Constructive debates and collaboration between industry and decision-makers are vital to achieve a harmonized HTA process for high-cost combination therapies which offer advanced benefits and improved safety outcomes, whilst satisfying HTA bodies and providing better access for patients.

Health technology assessment (HTA) must adapt to support the changing health system landscapes and improve access to valuable innovation under budgetary constraints. This is exemplified by the pricing and reimbursement of high-cost combination therapies increasingly used in oncology. Variability exists in current HTA practices across different countries, resulting in discrepancies in reimbursement outcomes and patient access. Using Italy as a case study, the objective was to assess the challenges faced by HTA agencies in the negotiation of pricing and reimbursement of combination therapies.

A targeted literature review of Italian HTA agency websites was undertaken to identify any literature/guidance relating to HTA decision-making for combination oncology therapies.

In Italy, there is no fixed cost-effectiveness threshold and decisions are based on multiple criteria. Managed market entry agreements are extensively used; price-volume agreements and drug registries are common. While this framework allows flexibility and avoids the rigidity of incremental cost-effectiveness ratio thresholds, it has raised concerns about transparency and budget impact. Combination therapies are not given specific concessions; however, market access for a combination of a new high-cost drug with an existing one is complex, particularly if the drugs are manufactured by different companies. The added value provided by the new drug in the combination should be rewarded while the older product benefits from the increased volume of use. The price of the older drug cannot be lowered unless the pricing and reimbursement contract is expiring or a new indication/formulation is pending, presenting a challenge to both pharmaceutical companies and HTA agencies.

Combination therapies pose a challenge for HTA agencies. In the Italian system this is partially mitigated by the use of multiple criteria for decision-making and managed access agreements. However, these approaches have also led to concerns about a lack of transparency in decision-making.

Re-purposing of established products (EPs) – defined as marketed for 8 years or more – may represent a high value for patients and society. It has been recognized by the European Commission as an important factor contributing to greater access to new therapies. Due to a lower development cost, it could also represent a cost-effective alternative and help to reduce pressure on healthcare budgets. However, it is perceived that no financial incentives exist for the pharmaceutical industry to invest in new indications for EPs. The objective of this research was to review current European regulations and propose strategies stimulating development in this field.

We performed a targeted literature review and held two international expert panel workshops to discuss current policies and their implications, and issue recommendations for changes.

Within the current regulatory framework EPs face price cuts due to generic competition, reference pricing (RP), price re-negotiations or systematic price cuts, after a period of marketing presence. Extension of indications does not permit to increase or maintain the price. Generic substitution regardless of indication poses another challenge. Limited incentives in the form of an additional year of market protection exists only for new indication(s) registered within the first 8 years following initial approval. The expert panel proposed several strategies to stimulate development in this field, including: (i) extending the period in which registering a new indication results in additional market protection beyond 8 years and extending the duration of additional market protection; (ii) delaying inclusion in RP for EPs with a new value adding indication; (iii) establishing a differential pricing by indication; (iv) preventing temporarily generic substitution when an EP is prescribed for a new indication.

Current regulations represent a serious disincentive to develop new indications for EPs. Regulatory and pricing policy changes are needed to stimulate development in this important field.

Objective – The objectives of the paper are the following: i) to describe the activities and the costs of care for patients with severe mental disorders; ii) to evaluate the association between costs, clients' characteristics and outcome measures. Methods – Patients were administered the following instruments twice a year: BPRS, GAF, HoNOS, DAS II, VSSS-54, QPF. Use of psychiatric services and other resources were collected for each patient over a two-year period. Results – The average yearly cost per patient is Euro 3,300. First-contact patients cost twice as much as patients already in treatment. Service costs are associated to patients' age, marital status and working condition. Annual costs are also associated with the initial score of BPRS, GAF, DAS and HoNOS. In multiple regression analysis age, initial BPRS and DAS scores, as well as being a first-contact patient, are strongly positively associated to annual costs. Conclusions – These results highlight the importance of monitoring routine activities of psychiatric services and the flow of funds for psychiatric care in the Italian public health system.

Declaration of Interest: the research project was funded by a grant from the Lombardy Region Health Authority.