A Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products.

Purpose: Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims. Given their pivotal role in bridging Advanced Therapy Medicinal Products (ATMPs) to patients, their foreseeable future implementation calls for a specific investigation of their associated challenges and opportunities. Therefore, this work aims to identify challenges and opportunities in implementing MEAs specifically for ATMPs.

Methods: A systematic literature review was conducted on PubMed, MEDLINE, Scopus, and Google Scholar, based on the updated Preferred Reporting Items for Systematic Review and Meta-Analysis. This has been supplemented by a snowball search. Through the thematic content analysis, opportunities and challenges were identified and grouped into themes and subthemes. Afterward, the subgroup analysis was performed to investigate challenges and opportunities with outcome-based agreements (OBAs) versus financial-based agreements (FBAs), jurisdiction, and ATMP type.

Findings: Of the 787 peer-reviewed articles, 42 met the inclusion criteria. Challenges and opportunities were clustered into the mentioned themes: evidence generation and data management, financial and reimbursement, administration and resources, negotiation, and governance, law, and regulations. Of note, no specific challenges or opportunities were found to be cell- or gene-therapy-specific, but certain challenges seem amplified for ATMPs. Several differences emerged per MEA type and jurisdiction. OBAs are described to reward innovative and effective treatments and boost research and development (R&D) returns. FBAs improve cost-effectiveness ratios but can negatively affect curative ATMP's revenues. Still, their versatility facilitates payer engagement in MEA combinations (eg, OBA with spread payments). The US decentralized health care system reported additional implementation challenges to OBAs. Each payer internally decides on reimbursement, and coordination among private payers is hindered by antitrust law. Yet, a new Cell and Gene Therapy Access model has been proposed. This would allow manufacturers to negotiate OBAs directly with the Centers for Medicare & Medicaid Services avoiding individual negotiation with each state. In Europe, there is an evident interest in implementing spread payments, yet accounting rules currently hamper their implementation.

Implications: This work offers insights into challenges and opportunities in MEAs implementation for ATMPs by investigating differences in MEA types and jurisdictions. Our findings provide significant insights that may help move successful MEA implementation forward, improving patient access to ATMPs.