International reference pricing has been a talking point for elected officials and Department of Health and Human Services leaders in the U.S. for nearly a decade, but President Donald Trump’s May 2025 executive order pushed for broader and faster adoption than many industry experts anticipated.

By the end of 2025, 14 of the 17 large drugmakers addressed by the White House had signed voluntary agreements to offer newly launched medicines in the U.S. at prices comparable to those in other high-income countries and make existing drugs available to Medicaid patients at most-favored-nation (MFN) prices. The three remaining manufacturers soon followed, along with nine other companies, bringing participation up to approximately 89% of the branded market in just over a year of the executive order’s publication. An early signal of MFN’s impact is an apparent decrease in new drug launches in EU markets, with one source estimating that launches declined roughly 35% year over year during that time period.

The introduction of MFN pricing represents one of the most consequential changes to pricing and access policies the U.S. pharmaceutical market has seen in years, but it is by no means the only major shift across the commercialization landscape. The EU’s Joint Clinical Assessment (JCA) process is raising the bar for comparative evidence standards, while national Health Technology Assessment (HTA) bodies such as NICE and Germany’s G-BA are scrutinizing evidence more closely and making greater use of real-world evidence (RWE) to supplement clinical trial data. Around the globe, market forces and supply chains are becoming increasingly volatile and interdependent. As they do, pharmaceutical decision-makers must navigate increasingly complex trade-offs with significant downside risk.

“Today’s complexity means that pharmaceutical leaders can no longer think in terms of sequential steps when they’re planning a launch strategy,” said Michael Day, Ph.D., senior director of regulatory strategy and CMC at Cencora. “You can’t optimize your regulatory path and then product safety and then market access and commercialization and expect the best possible global outcome. Sometimes the best regulatory path is not the best path to the market. In this world, all the different disciplines need to work together for a common cause.”

Scenario modeling — the practice of building and testing multiple forecasts based on a variety of assumptions about policies, competition and global markets — is an essential tool for decision-makers tasked with charting a course through these kinds of uncertainties. But most pharmaceutical companies still model scenarios using a single-threaded approach — that is, one function at a time — with each department working in isolation, using its own model and assumptions.

What’s needed for success is an integrated approach to scenario modeling and analysis, one that incorporates data gathered across the entire organization, breaks down the silos between departments and disciplines, and leverages newer technologies such as AI to manage the additional complexity.

Planning for commercialization in a borderless global market

JCA provides a joint scientific assessment of the relative clinical effectiveness and safety of a medicine compared with alternatives, but it does not determine pricing, reimbursement or overall value. National HTA bodies are required to give the JCA due consideration during their own country-specific assessments, alongside economic, healthcare-system and other concerns. A JCA report showing uncertainty about comparators, endpoints or generalizability can make payers more cautious and weaken your value story. Manufacturers need to consider this interdependency from the earliest phases of development.

They should also design an evidence plan that will satisfy both national payers and regulators. A clinical development program may be sufficient to support regulatory approval but still leave gaps for JCA or national HTA if it does not generate the comparative evidence needed against relevant standards of care. And because JCA is now conducted in parallel with EMA review, that evidence must be ready at the time of submission.

“In the past, manufacturers could choose which countries to make HTA submissions in, and they could base this decision on what kinds of data they had available,” explained Casper Paardekooper, vice president for health policy and strategy at Cencora. “Now, when they take part in the European clinical assessment process, as many as 27 different countries can have input into the PICOs (Population, Intervention, Comparator and Outcome) that serve as evidence in the JCA. To be successful in this process, you have to plan to include an array of comparators, endpoints and subpopulations in your research, and you need to have the evidence ready early on.”

In the current climate, European national pricing outcomes can not only sway other EU countries’ HTA bodies but also influence negotiations elsewhere, including the U.S. Prices in other parts of the world are interconnected, too. Several countries in Southeast Asia use reference pricing based on prices in European countries, while Australia is a major reference input for Canada.

“MFN and international reference pricing mean that what we do in one local market no longer only has local consequences,” Day said.

Reimagining scenario modeling for this new era

Many drugmakers still maintain separate U.S. and European launch teams, with each conducting its own pricing research and payer intelligence. In today’s world, the potential trade-offs involved in launch sequencing make this traditional approach untenable.

In integrated scenario modeling, policy, regulatory and CMC, market access, medical, clinical, and pharmacovigilance teams all provide input, making it possible to test scenarios that no single function could evaluate on its own:

• If you launch first in the U.S., should you still launch in Europe, Japan and Canada?

• 如果是这样，应按什么顺序？
• 为了在欧洲获得更大销量，你能接受多大的美国定价风险？

AI 支持的分析可以通过综合大量数据和证据，帮助使集成情景建模更具可扩展性，使团队能够考察比人工操作更广泛的情景。随着假设、证据和市场状况变化，它还可以帮助团队更高效地更新这些情景。

不过，AI 并不能取代专家判断。“AI 可以生成大量不同的情景，但人类专家仍然需要理解这些情景意味着什么，”Day 说。“不确定性越大，所需的思维多样性就越大。制药公司将需要变得越来越敏捷，并能够在监管要求或市场发生变化时迅速转向。”

“战略前瞻正日益成为制药公司内部最关键的能力，”Paardekooper 补充道。

尽早开始

集成规划最好在产品开发的最早阶段启动。到上市时，再对终点选择或临床数据策略作出关键更改已为时过晚。要最大化研发投资回报，需要尽快将新疗法带给患者。如果没有跨学科、相互连通的策略，就存在延迟风险——甚至患者可能完全无法获得新疗法。

“你越早考虑这些事情并将它们整合起来，就越能在开发项目中建立灵活性，”Day 补充道。“这种灵活性使制药商能够在更清楚地了解下游后果的情况下作出关键决策。这是成功的基础。”

在 Cencora 的最新报告中进一步了解正在重塑全球上市策略的市场力量。