Mapping the landscape of managed entry agreements: a systematic review of global frameworks, system-level components, and implementation challenges.

BACKGROUND

Managed Entry Agreements (MEAs) are pivotal for enabling access to innovative pharmaceuticals while mitigating financial risk and addressing evidence uncertainty. Despite conceptual acceptance, the essential requirements for their design and implementation are poorly documented, posing a challenge for evolving health systems. This study aimed to systematically review and map global evidence published in the literature on the existence and characterization of countries' MEA policies, focusing on the core system-level components, governance, and operational frameworks for successful implementation, and their associated development and implementation challenges.

METHODS

A systematic review was conducted following PRISMA guidelines. MEDLINE and EMBASE were searched from inception to March 2025. Studies discussing governance, frameworks, legislation, or implementation of pharmaceutical MEAs were included. Data were extracted and synthesized narratively.

RESULTS

Of 96 included studies, most focused on European (43%) and North American (28%) systems, with a significant evidence gap for the Middle East and low-income countries. While situational analysis was the most common theme (63%), the literature predominantly catalogued barriers rather than providing operational solutions. Key barriers were inefficient regulatory frameworks (identified in 42% of studies), data infrastructure limitations (41%), and high administrative burden (38%). Stakeholder analysis highlighted underrepresentation of academia and civil society. A minority of studies (15%) focused on Advanced Therapy Medicinal Products (ATMPs).

CONCLUSION

This review identifies a critical "how-to" gap in the MEA literature. While the value of MEAs is acknowledged, there is a stark deficit of actionable, system-level guidance on the regulatory, governance, and operational prerequisites for implementation. For health systems seeking to adopt MEAs, future efforts must shift from describing barriers to developing concrete implementation toolkits, legislative roadmaps, and fit-for-purpose payment models.