The EU HTA Regulation, Regulation 2021/2282 in force since January 12, 2025 for new active substances in oncology and for all Advanced Therapy Medicinal Products, is the single most important change in the European pharma market access framework of the last decade. The phase-in foreseen by the regulation extends the scope over time: in 2026 some high-risk medical devices enter the scope, from January 2028 orphan medicines, from 2030 all centrally authorized medicines. The operational effect for pharmaceutical companies is the transformation of the Joint Clinical Assessment into a tool of scientific harmonization with significant national consequences.
The first six quarters of HTAR application have shown the real numbers of the new model. The PICO matrix that each dossier must cover — Population, Intervention, Comparator, Outcome — explodes as a function of the combinations that Member States require: the simulation on IMFINZI generated thirteen PICOs from seven populations and six comparators, but other products have reached thirty PICOs. Manufacturers have approximately ninety to one hundred days from PICO matrix consolidation to complete dossier submission, with fifteen days to respond to additional data requests. Real dossiers have reached thirty thousand pages. The sources of these findings — Trinity Life Sciences in 2025, Remap Consulting, DIA Global Forum in its August 2025 issue, ICON in March 2026 — converge on the same picture: the constraint is not scientific, it is documentary production at a sustainable speed.
ESMO-MCBS v2.0 as lingua franca
The ESMO Magnitude of Clinical Benefit Scale, in its version 2.0 published in Annals of Oncology in 2025, has become the shared reference for the assessment of oncology clinical benefit in the JCA context. The methodological revision redistributed scores in 13.6% of re-evaluated studies — 10.5% downgrades and 3.1% upgrades — and added toxicity annotations to 45.5% of studies in curative settings. A study published in Lancet Oncology in December 2024 documented the correlation between high MCBS scores and positive HTA outcomes, with shorter times to reimbursement. For oncology pharmaceutical companies the message is clear: the MCBS system is the shared language through which European payers converge on value assessment, and optimizing one's own evidence in an MCBS-coherent way is a choice that directly impacts access outcome.
The reverse message is equally relevant: products with low MCBS scores that manage to obtain a positive price in national systems are decreasing. The political pressure on the JCA, which some analysts have described as "PICO scope-creep" — the inclusion of comparators chosen to push the price downward — produces a further consequence: the difference in the quality-price ratio of products is assessed with standardized tools at the European level, while the final price negotiation remains national. It is a model that amplifies the value of companies with solid dossiers and penalizes those with marginal evidence.
AI in HTA dossiers: Cytel, Genesis, Cochrane RAISE
AI applied to HTA dossier preparation is one of the most dynamic segments of 2025-2026. Cytel has published ELEVATE-GenAI, a reporting guideline for the use of generative AI in Health Economics and Outcomes Research workflows. Genesis Research, after the 2024 acquisition of Market Access Transformation, which brought headcount from 145 to 215 people, has developed EVID AI, an evidence synthesis platform. Cochrane launched in 2025 the RAISE framework — Recommendations for AI in Evidence Synthesis — developed jointly with Campbell, Joanna Briggs Institute and Collaboration for Environmental Evidence, which endorses the use of AI in evidence synthesis with mandatory human oversight. The Cochrane platform study at the end of 2025 selected Laser AI and Nested Knowledge among the 48 candidate submissions.
The operational level at which these tools produce measurable value is that of systematic literature reviews. The SLR is the evidence base feeding the HTA dossier: in traditional processes it requires weeks of work by specialized abstractors for screening thousands of papers, endpoint extraction, quality assessment, and quantitative synthesis. AI-driven tools reduce the cycle to days while preserving, according to the benchmarks published in 2025, equivalent quality with human supervision. The cumulative gain on a JCA dossier of thirty thousand pages is not marginal: it changes the feasibility of meeting the ninety-day window from PICO consolidation.
AIFA Resolution 88/2025: Italy's April 1, 2026
AIFA approved on December 23, 2025 Resolution 88/2025, which modernizes the Italian HTA guidelines, with operational effect from April 1, 2026. The provision, which complements the Ministerial Decree of July 21, 2022 on simplified and fast-track procedures for generics and biosimilars, aligns the national framework with JCA dynamics by opening up to evidence beyond the randomized controlled trial — Real World Evidence first — and simultaneously raising the bar on the documentary quality of the dossier. The E-Dossier portal for pricing and reimbursement submissions is mandatory. The operational message for Italian pharmaceutical companies is twofold: greater acceptability of evidence other than trials, but more stringent documentary and traceability standards.
AIFA Resolution 88/2025 is the first structural evolution of the Italian P&R negotiation framework after the 2020 update and arrives at a time when the national health system manages EUR 26.8 billion in public pharma spending in 2024, grown 7.7% year on year according to OsMed. For Italian market access managers, 2026 is a year of transformation on two parallel tracks: alignment to the European JCA matrix for centrally authorized products and adaptation to the new national framework for final price negotiation. The deadlines converge in the same semester.
The two-speed risk
The picture that emerges from the first real JCA dossiers contains a strategic risk that analysts have started calling "two-speed market access". Large pharma with consolidated HEOR structures, enterprise documentary capacity, access to AI evidence synthesis platforms, and JCA-dedicated teams produce thirty-thousand-page dossiers in ninety days while maintaining competitive quality. Mid-market companies and European biotechs with leaner commercial structures face a fixed cost of documentary production that does not scale with the size of their portfolio, and that risks compromising the feasibility of their European registration roadmap.
The EU AI Act introduces a third constraint that intersects with market access in a non-trivial way. When an AI system is used to produce evidence submitted to an HTA authority with decision-making power over market access — Joint Clinical Assessment, AIFA, NICE, G-BA, HAS — the system potentially falls within the high-risk regime applicable from August 2, 2026. Technical documentation, model monitoring, human oversight, and audit trail become regulatory obligations, not just best practice. For the system integrator that supports an Italian pharmaceutical company on its HTA journey, 2026 is the year in which regulatory know-how on the AI Act becomes part of its value proposition. Not an add-on. A project specification.
