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

Abstract

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.

Keywords:

• Early access programs
• Off-label
• Medicines
• France
• Italy
• Spain
• UK

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s40545-023-00570-z.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s40545-023-00570-z.

Acknowledgements

We are grateful to all local experts for having supported us in integrating information retrieved from the literature.

Editorial assistance

The revision of the English text was provided by Helen Banks (Cergas Bocconi, Milano, Italy).

Author contributions

Concept and design: CJ and MHO. Acquisition of data: AT and MHO. Analysis and interpretation of data: CJ, AT, MHO, PA, FC, FM. Drafting of the manuscript: AT, CJ, MHO. Obtaining funding: CJ, and MHO. Administrative, technical, or logistic support: not needed. Supervision: CJ, MO. All authors read and approved the final manuscript.

Funding

The research was funded by an unrestricted grant from a pool of pharmaceutical companies supporting the research activities of the Pharmaceutical Observatory at Cergas Bocconi (Abbvie, AstraZeneca, Bayer, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Janssen Cilag, Lundbeck, Merck Sharp & Dohme, Novartis, Roche, Pfizer, Sanofi, Takeda, Teva).

Declarations

Competing interests

Claudio Jommi reported serving as an advisory board member and a paid speaker for Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, CSL Behring, Gilead, Incyte, Merck Sharp & Dohme, Roche, Sanofi, Takeda, outside the submitted work. All other authors have not any conflict of interest to declare.

Supplementary Information

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