SYSTEMATIC LITERATURE REVIEW OF GLOBAL FRAMEWORKS FOR MANAGED ENTRY AGREEMENTS: IMPLEMENTATION REQUIREMENTS AND CHALLENGES
Author(s)
Hussain Abdulrahman Al-Omar, MSc, PhD1, Asma A. Al-Muhsin, II, MSc2, Lolwa Almudaiyan3, AMAL Hassan AL-NAJJAR, DPhil4, Laila Abu Esba5, Hind Almodaimegh6, Jehan Alamre7, Consuela Yousef8, MANSOOR KHAN9, Khalid AlYahya10, ESRAA ALTAWIL11, Abdualmajeed Binjumayah, MBA12, Faisal Alharbi, BSc12, Sultan Tawfiq AlShurbaji, Sr.13, Fatma Maraiki, MSc, PharmD, PhD, Other14, Jaime Espin, MSc, PhD15, Rosanna Tarricone, PhD16, Panos Kanavos, BSc, MSc, PhD17.
1College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, 2Ministry of Health Saudi Arabia, Riyadh, Saudi Arabia, 3Center for Health Technology Assessment, Riyadh, Saudi Arabia, Saudi Arabia, 4Health Technology Assessment Center, Riyadh, Saudi Arabia, 5KSA, Riyadh, Saudi Arabia, 6KAMC, Riyadh, Saudi Arabia, 7nDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi, Saudi Arabia, 8Ministry of National Guard – Health affairs, Saudi Arabia, 9National Guard Hospital, Jeddah, Saudi Arabia, 10Department of Pharmaceutical Service, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, Saudi Arabia, 11Riyadh, Saudi Arabia, 12Tawuniya Insurance Company, Riyadh, Saudi Arabia, 13University of York, York, United Kingdom, 14Alfaisal university, Riyadh, Saudi Arabia, 15EASP, Granada, Spain, 16Bocconi University, ROMA, Italy, 17London School of Economics and Political Science, London, United Kingdom.
1College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, 2Ministry of Health Saudi Arabia, Riyadh, Saudi Arabia, 3Center for Health Technology Assessment, Riyadh, Saudi Arabia, Saudi Arabia, 4Health Technology Assessment Center, Riyadh, Saudi Arabia, 5KSA, Riyadh, Saudi Arabia, 6KAMC, Riyadh, Saudi Arabia, 7nDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi, Saudi Arabia, 8Ministry of National Guard – Health affairs, Saudi Arabia, 9National Guard Hospital, Jeddah, Saudi Arabia, 10Department of Pharmaceutical Service, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, Saudi Arabia, 11Riyadh, Saudi Arabia, 12Tawuniya Insurance Company, Riyadh, Saudi Arabia, 13University of York, York, United Kingdom, 14Alfaisal university, Riyadh, Saudi Arabia, 15EASP, Granada, Spain, 16Bocconi University, ROMA, Italy, 17London School of Economics and Political Science, London, United Kingdom.
OBJECTIVES: Managed Entry Agreements (MEAs) are increasingly recognized globally as instruments that enable timely patient access to innovative pharmaceuticals while mitigating evidence uncertainties and/or financial risks. Nevertheless, the implementation of MEAs remains nascent in many settings, with no standardized frameworks and guiding principles, and a lack of standardized system-level requirements. This systematic review synthesizes published evidence on countries’ MEA policies, identifies the core system-level components, governance structures, and operational frameworks essential for successful implementation, and examines associated barriers and enablers, thereby informing MEA operationalization in evolving health systems.
METHODS: A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE and EMBASE were searched from inception to March 2025. Studies addressing the governance, frameworks, legislation, or implementation of pharmaceutical MEAs were included. Data were extracted and analyzed both thematically and descriptively.
RESULTS: Ninety-six studies were included. The majority represented European (43%) and North American (28%) contexts, with limited evidence from the Middle East and low-income settings. Most studies (63%) were situational analyses that emphasized barriers over structural solutions. Key implementation challenges identified were inadequate regulatory frameworks (42%), insufficient data infrastructure (41%), and high administrative burden (38%). Stakeholder analyses revealed limited involvement of academic institutions and civil society actors, and only 15% of studies addressed Advanced Therapy Medicinal Products.
CONCLUSIONS: This review highlights a significant evidence gap concerning the operational frameworks, regulatory mechanisms, and policy architecture required for MEA implementation, despite their widespread recognition. There is a pressing need for actionable, system-level guidance to ensure effective implementation, particularly in evolving health systems. Future research should prioritize closing this gap to support the concrete development and deployment of MEAs.
METHODS: A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE and EMBASE were searched from inception to March 2025. Studies addressing the governance, frameworks, legislation, or implementation of pharmaceutical MEAs were included. Data were extracted and analyzed both thematically and descriptively.
RESULTS: Ninety-six studies were included. The majority represented European (43%) and North American (28%) contexts, with limited evidence from the Middle East and low-income settings. Most studies (63%) were situational analyses that emphasized barriers over structural solutions. Key implementation challenges identified were inadequate regulatory frameworks (42%), insufficient data infrastructure (41%), and high administrative burden (38%). Stakeholder analyses revealed limited involvement of academic institutions and civil society actors, and only 15% of studies addressed Advanced Therapy Medicinal Products.
CONCLUSIONS: This review highlights a significant evidence gap concerning the operational frameworks, regulatory mechanisms, and policy architecture required for MEA implementation, despite their widespread recognition. There is a pressing need for actionable, system-level guidance to ensure effective implementation, particularly in evolving health systems. Future research should prioritize closing this gap to support the concrete development and deployment of MEAs.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HPR22
Topic
Health Policy & Regulatory, Health Technology Assessment, Medical Technologies
Topic Subcategory
Coverage with Evidence Development & Adaptive Pathways, Procurement Systems, Reimbursement & Access Policy, Risk-sharing Approaches
Disease
Biologics & Biosimilars, Genetic, Regenerative & Curative Therapies, Oncology, Rare & Orphan Diseases