Developer Engagement Misalignment: Challenges in Assessing Advanced Therapies
Advanced Therapy Medicinal Products (ATMPs) offer transformative options for rare and previously untreatable conditions, yet their high upfront costs, uncertain durability, and single-arm trial data create major reimbursement barriers. The 2026 pre-proof study by Greco et al. shows that developer engagement misalignment—especially among small and academic sponsors—systematically prevents evidence from matching payer needs, reducing the viability of outcome-based or hybrid Managed Entry Agreements (MEAs) and extending uncertainty.
Reimbursement Pathway Hurdles
The study maps adoption challenges across Health Technology Assessment (HTA), Appraisal and Decision Making, and Implementation. In HTA, experts in England, the Netherlands, and Spain cited difficulties defining endpoints for outcome-based agreements and extrapolating short-term data to long-term benefit. Late developer engagement worsens these gaps because comparative real-world data requirements are rarely built into EMA submissions. Appraisal negotiations drag on when response variability, logistics, and post-administration risks stay unresolved after marketing authorization. Implementation suffers from administrative load, fragmented data systems, and inflexible accounting rules that block spread payments or hybrid MEAs. These frictions hit small and academic developers hardest in rare-disease settings.
Capability Shortfalls in Small Developers
Participants stressed that small and academic developers frequently miss early dialogue windows, producing submissions that overlook key uncertainties or fail to propose measurable outcomes. In England, NICE horizon-scanning processes go unused when contact occurs too late. Similar delays appear in the Netherlands’ “lock” mechanism and Spain’s decentralized monitoring needs. The study’s prioritization exercise ranked administrative burden, outcome measurement, and data collection as top challenges across all three countries, showing that post-authorization MEAs alone cannot resolve evidence shortfalls.
Calls for Proactive Collaboration
Greco et al. urge evidence alignment ideally 18 months before CHMP recommendation to enable upstream comparative real-world data planning and EMA-HTA standard alignment. Hybrid MEAs tied to pre-specified outcomes were seen as promising if accounting rules allow deferred payments and interoperable registries are created. Stronger pre-approval collaboration among HTA bodies, manufacturers, clinicians, and patient groups was viewed as essential to cut negotiation delays and ensure ethical oversight of long-term risks. Despite the EU HTA Regulation, persistent fragmentation requires coordinated national and international action.
Broader Impacts on HEOR and Policy
These findings directly affect Health Economics and Outcomes Research practice and market-access strategies. Manufacturers—particularly smaller developers—must embed HTA perspectives into clinical programs much earlier. Payers can support this shift by publishing clearer evidence templates and expanding early scientific advice. Policymakers should invest in interoperable data systems and consider centralized negotiation platforms. Greco et al. conclude that sustainable ATMP access depends on aligning evidence generation with decision-maker needs before authorization rather than expanding post-hoc schemes. Coordinated early engagement remains the most credible path to feasible MEAs and health-system sustainability.
The Greco et al. 2026 study delivers a rare multi-jurisdiction view of decision-maker experience and positions developer engagement misalignment as a root cause that stakeholders can address through earlier, structured dialogue.
