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 ((sic) 81.2 million in 2021; average cost per patient (sic) 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.

Automated summary

This study compares early access programs (EAPs) in four European countries (France, Italy, Spain, UK) and provides empirical evidence on EAPs in Italy. Although EAPs differ across countries, they share some common features such as eligibility criteria, budget allocation, and unknown total spending. France has the most structured EAPs, funded through social insurance, covering pre-marketing, post-marketing, and pre-reimbursement phases, and collecting data. Italy has diverse EAP approaches, with programs covered by different payers, including the cohort-based 648 List, the nominal-based 5% Fund, and Compassionate Use. Harmonizing these programs based on the French model could help reduce inequalities in access to medicines in Europe.