Early access programs for medicines: comparative analysis among France, Italy, Spain, and UK and focus on the Italian case.

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk-benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy's approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs.

How to improve efficiency in cancer care: Dimensions, methods, and areas of evaluation.

Efficiency in healthcare is crucial since available resources are scarce, and the cost of inefficient allocation is measured in prior outcomes. This is particularly relevant for cancer. The aim of this paper is to gain a comprehensive overview of the areas and dimensions to improve efficiency, and establish the indicators, different methods, perspectives, and areas of evaluation, to provide recommendations for how to improve efficiency and measure gains in cancer care. METHODS: We conducted a two-phase design. First, a comprehensive scoping literature review was conducted, searching four databases. Studies published between 2000 and 2021 were included if they described experiences and cases of efficiency in cancer care or methods to evaluate efficiency. The results of the literature review were then discussed during two rounds of online consultation with a panel of 15 external experts invited to provide insight and comments to deliberate policy recommendations. RESULTS: 46 papers met the inclusion criteria. Based on the papers retrieved we identified six areas for achieving efficiency gains throughout the entire care pathway and, for each area of efficiency, we categorized the methods and outcomes used to measure efficiency gain. CONCLUSION: This is the first attempt to systemize a scattered body of literature on how to improve efficiency in cancer care and identify key areas of improvement. POLICY SUMMARY: There are many opportunities to improve efficiency in cancer care. We defined seven policy recommendations on how to improve efficiency in cancer care throughout the care pathway and how to improve the measurement of efficiency gains.

Implementation of Value-based Pricing for Medicines.

Value-based pricing (VBP) is well established in markets for common goods and services, but wide consensus on VBP for pharmaceuticals is lacking. In principle, VBP implies that prices are mainly driven by a drug's value (value for money) and that the impact on budget (sustainability) is a second-order driver of price regulation. Although the literature provides descriptive analyses on regulations governing medicine price negotiation, there are few insights on whether and how price negotiation regulations have been implemented. The goal of this article was to cover this information gap for 5 European countries and the United States. VBP has been applied according to two models: (1) direct models in which cost-effectiveness is a driver; and (2) indirect, multi-attribute models characterized by greater discretion on the integration between the different value domains and the evaluation of consistency between costs and value. In these models, cost-effectiveness is not a driver. In addition, it is hard to evaluate within these models the actual implementation of VBP. Identifying whether and how VBP is applied requires a clear predefined link between added value and the premium price, as well as transparency in the way added value is converted into a premium price. In general, for these countries, it remains difficult to determine whether pricing is mostly driven by value (value-for-money) or impact on budget (sustainability). In instances in which thresholds on the incremental cost-effectiveness ratio are used, it becomes easier to understand whether VBP has been implemented. If VBP relies on a multi-criteria approach, greater transparency on which criteria have been used to assess a new drug and how they have been converted into a reasonable price may help in understanding whether a value-based approach has been used.

Corrigendum: The Economic Impact of a Switch From Prescription-Only to Non-prescription Drugs in Italy.

[This corrects the article DOI: 10.3389/fphar.2018.01069.].

The Economic Impact of a Switch From Prescription-Only to Non-prescription Drugs in Italy.

The paper analyses the potential economic impact of switching drugs from prescription-only to over the counter status, using Italy as a case-study. The study assumes a societal perspective, investigating the effects of switches (and consequent delisting) on drugs spending, avoided visits by GPs (General Practitioners) and avoided time spent by patients for these visits. It overcomes the main pitfalls of previous studies, providing a rational for listing switchable products and applying both a static (no impact of switch on prices and volumes consumed) and a dynamic approach (impact on pricing policies and volumes depending on price-elasticity). Different scenarios were assumed including shorter/longer time spent for visits and inclusion/exclusion of the economic value of time of retiree patients. Results show that switching policy provides with societal savings ranging from 1 to 2.1 1 billion Euro. The economic impact on patients is less straightforward and depends on the scenarios used. If a longer time is spent on visits, the economic value of this time will compensate the cost of the switch to patients due to delisting. Despite the net economic benefit should be carefully interpreted, the results demonstrate how switching can contribute to the sustainability of the health care system in the middle-long run thanks to the more rational use of resources, combined with an increased awareness and responsibility of the involved stakeholders.

Variations in non-prescription drug consumption and expenditure: Determinants and policy implications.

This paper analyses the determinants of cross-regional variations in expenditure and consumption for non-prescription drugs using the Italian Health Care Service as a case study. This research question has never been posed in other literature contributions. Per capita income, the incidence of elderly people, the presence of distribution points alternative to community pharmacies (para-pharmacies and drug corners in supermarkets), and the disease prevalence were included as possible explanatory variables. A trade-off between consumption of non-prescription and prescription-only drugs was also investigated. Correlation was tested through linear regression models with regional fixed-effects. Demand-driven variables, including the prevalence of the target diseases and income, were found to be more influential than supply-side variables, such as the presence of alternative distribution points. Hence, the consumption of non-prescription drugs appears to respond to needs and is not induced by the supply. The expected trade-off between consumption for prescription-only and non-prescription drugs was not empirically found: increasing the use of non-prescription drugs did not automatically imply savings on prescription-only drugs covered by third payers. Despite some caveats (the short period of time covered by the longitudinal data and some missing monthly data), the regression model revealed a high explanatory power of the variability and a strong predictive ability of future values.

The simultaneous effects of pharmaceutical policies from payers' and patients' perspectives: Italy as a case study.

OBJECTIVES: This paper aims at covering a literature gap on the effects of copayments, prescription quotas and therapeutic reference pricing on public and private expenditures and volumes (1) When these policies are implemented in different areas at different times, (2) estimating their impact in the short and long run, (3) assessing the extent to which these impacts are interdependent, (4) scrutinising the extent to which the effects are mediated by prescribers' and patients' behaviours. METHODS: Monthly regional data on pharmaceutical expenditures, volumes and policies in Italy from 2000 to 2014 are analysed using a difference-in-differences model enriched to capture short- versus long-term effects and simultaneous and interactive effects. Sobel-Goodman test and bootstrap analyses were used to test for mediation. RESULTS: The three policies have different short- and long-run effects. Interactions support the hypothesis of reinforcing effects. Behavioural reactions to policies such as reducing the demand or total per capita expenditures mediate the impact of policies, thus explaining the different effects between the short and long term. CONCLUSIONS: Evidence on the impact over time of regional policies diversely introduced in different times have important policy implications. First, pharmaceutical policies interact with each other, and the combined effect may be different from what we would expect from the sum of each single policy. Hence, policymakers should be very careful in designing mixed policies for their unexpected combined effects. Second, the impact of policies tends to reduce over time. If longer-term impact is desired, it would be appropriate to introduce some adjustments over time. Third, policies have multiple effects, and this should be considered when they are designed. Finally, pharmaceutical policies may have an unintended impact on health and health care.