Thirty-six million Europeans — including more than one million in the Nordics[1] — live with a rare disease.[2] For patients and their families, this is not just a medical challenge; it is a human rights issue. Diagnostic delays mean years of worsening health and needless suffering. Where treatments exist, access is far from guaranteed. Meanwhile, breakthroughs in genomics, AI and targeted therapies are transforming what is possible in health care. But without streamlined systems, innovations risk piling up at the gates of regulators, leaving patients waiting. Even the Nordics, which have some of the strongest health systems in the world, struggle to provide fair and consistent access for rare-disease patients. Expectations should be higher. THE BURDEN OF DELAY The toll of rare diseases is profound. People living with them report health-related quality-of-life scores 32 percent lower than those without. Economically, the annual cost per patient in Europe — including caregivers — is around €121,900.[3] > Across Europe, the average time for diagnosis is six to eight years, and > patients continue to face long waits and uneven access to medications. In Sweden, the figure is slightly lower at €118,000, but this is still six times higher than for patients without a rare disease. Most of this burden (65 percent) is direct medical costs, although non-medical expenses and lost productivity also weigh heavily. Caregivers, for instance, lose almost 10 times more work hours than peers supporting patients without a rare disease.[4] This burden can be reduced. European patients with access to an approved medicine face average annual costs of €107,000.[5] Yet delays remain the norm. Across Europe, the average time for diagnosis is six to eight years, and patients continue to face long waits and uneven access to medications. With health innovation accelerating, each new therapy risks compounding inequity unless access pathways are modernized. PROGRESS AND REMAINING BARRIERS Patients today have a better chance than ever of receiving a diagnosis — and in some cases, life-changing therapies. The Nordics in particular are leaders in integrated research and clinical models, building world-class diagnostics and centers of excellence. > Without reform, patients risk being left behind. But advances are not reaching everyone who needs them. Systemic barriers persist: * Disparities across Europe: Less than 10 percent of rare-disease patients have access to an approved treatment.[6] According to the Patients W.A.I.T. Indicator (2025), there are stark differences in access to new orphan medicines (or drugs that target rare diseases).[7] Of the 66 orphan medicines approved between 2020 and 2023, the average number available across Europe was 28. Among the Nordics, only Denmark exceeded this with 34. * Fragmented decision-making: Lengthy health technology assessments, regional variation and shifting political priorities often delay or restrict access. Across Europe, patients wait a median of 531 days from marketing authorization to actual availability. For many orphan drugs, the wait is even longer. In some countries, such as Norway and Poland, reimbursement decisions take more than two years, leaving patients without treatment while the burden of disease grows.[8] * Funding gaps: Despite more therapies on the market and greater technology to develop them, orphan medicines account for just 6.6 percent of pharmaceutical budgets and 1.2 percent of health budgets in Europe. Nordic countries — Sweden, Norway and Finland — spend a smaller share than peers such as France or Belgium. This reflects policy choices, not financial capacity.[9] If Europe struggles with access today, it risks being overwhelmed tomorrow. Rare-disease patients — already facing some of the longest delays — cannot afford for systems to fall farther behind. EASING THE BOTTLENECKS Policymakers, clinicians and patient advocates across the Nordics agree: the science is moving faster than the systems built to deliver it. Without reform, patients risk being left behind just as innovation is finally catching up to their needs. So what’s required? * Governance and reforms: Across the Nordics, rare-disease policy remains fragmented and time-limited. National strategies often expire before implementation, and responsibilities are divided among ministries, agencies and regional authorities. Experts stress that governments must move beyond pilot projects to create permanent frameworks — with ring-fenced funding, transparent accountability and clear leadership within ministries of health — to ensure sustained progress. * Patient organizations: Patient groups remain a driving force behind awareness, diagnosis and access, yet most operate on short-term or volunteer-based funding. Advocates argue that stable, structural support — including inclusion in formal policy processes and predictable financing — is critical to ensure patient perspectives shape decision-making on access, research and care pathways. * Health care pathways: Ann Nordgren, chair of the Rare Disease Fund and professor at Karolinska Institutet, notes that although Sweden has built a strong foundation — including Centers for Rare Diseases, Advanced Therapy (ATMP) and Precision Medicine Centers, and membership in all European Reference Networks — front-line capacity remains underfunded. “Government and hospital managements are not providing  resources to enable health care professionals to work hands-on with diagnostics, care and education,” she explains. “This is a big problem.” She adds that comprehensive rare-disease centers, where paid patient representatives collaborate directly with clinicians and researchers, would help bridge the gap between care and lived experience. * Research and diagnostics: Nordgren also points to the need for better long-term investment in genomic medicine and data infrastructure. Sweden is a leader in diagnostics through Genomic Medicine Sweden and SciLifeLab, but funding for advanced genomic testing, especially for adults, remains limited. “Many rare diseases still lack sufficient funding for basic and translational research,” she says, leading to delays in identifying genetic causes and developing targeted therapies. She argues for a national health care data platform integrating electronic records, omics (biological) data and patient-reported outcomes — built with semantic standards such as openEHR and SNOMED CT — to enable secure sharing, AI-driven discovery and patient access to their own data DELIVERING BREAKTHROUGHS Breakthroughs are coming. The question is whether Europe will be ready to deliver them equitably and at speed, or whether patients will continue to wait while therapies sit on the shelf. There is reason for optimism. The Nordic region has the talent, infrastructure and tradition of fairness to set the European benchmark on rare-disease care. But leadership requires urgency, and collaboration across the EU will be essential to ensure solutions are shared and implemented across borders. The need for action is clear: * Establish long-term governance and funding for rare-disease infrastructure. * Provide stable, structural support for patient organizations. * Create clearer, better-coordinated care pathways. * Invest more in research, diagnostics and equitable access to innovative treatments. Early access is not only fair — it is cost-saving. Patients treated earlier incur lower indirect and non-medical costs over time.[10] Inaction, by contrast, compounds the burden for patients, families and health systems alike. Science will forge ahead. The task now is to sustain momentum and reform systems so that no rare-disease patient in the Nordics, or anywhere in Europe, is left waiting. -------------------------------------------------------------------------------- [1] https://nordicrarediseasesummit.org/wp-content/uploads/2025/02/25.02-Nordic-Roadmap-for-Rare-Diseases.pdf [2] https://nordicrarediseasesummit.org/wp-content/uploads/2025/02/25.02-Nordic-Roadmap-for-Rare-Diseases.pdf [3] https://media.crai.com/wp-content/uploads/2024/10/28114611/CRA-Alexion-Quantifying-the-Burden-of-RD-in-Europe-Full-report-October2024.pdf [4] https://media.crai.com/wp-content/uploads/2024/10/28114611/CRA-Alexion-Quantifying-the-Burden-of-RD-in-Europe-Full-report-October2024.pdf [5] https://media.crai.com/wp-content/uploads/2024/10/28114611/CRA-Alexion-Quantifying-the-Burden-of-RD-in-Europe-Full-report-October2024.pdf [6] https://www.theparliamentmagazine.eu/partner/article/a-competitive-and-innovationled-europe-starts-with-rare-diseases? [7] https://www.iqvia.com/-/media/iqvia/pdfs/library/publications/efpia-patients-wait-indicator-2024.pdf [8] https://www.iqvia.com/-/media/iqvia/pdfs/library/publications/efpia-patients-wait-indicator-2024.pdf [9] https://copenhageneconomics.com/wp-content/uploads/2025/09/Copenhagen-Economics_Spending-on-OMPs-across-Europe.pdf [10] https://media.crai.com/wp-content/uploads/2024/10/28114611/CRA-Alexion-Quantifying-the-Burden-of-RD-in-Europe-Full-report-October2024.pdf Disclaimer POLITICAL ADVERTISEMENT * The sponsor is Alexion Pharmaceuticals * The entity ultimately controlling the sponsor: AstraZeneca plc * The political advertisement is linked to policy advocacy around rare disease governance, funding, and equitable access to diagnosis and treatment across Europe More information here.

Donald Trump is trying to purge United States research institutions of scholars who study purportedly progressive issues.  The European Union is tripping over itself to take them in.  From universities to cities, regions, countries and now the European Commission, the message is loud and clear — Europe welcomes U.S.-based talent and is pulling out all the stops to attract America’s best and brightest. “This global landscape is an opportunity to show the world that Europe will remain a safe space for science and research,” European Commissioner for Startups, Research and Innovation Ekaterina Zaharieva told EU lawmakers on Monday evening. “Europe can and should be the best place to do science … a place that attracts and retains researchers, both international and European.” Citing significant cuts to federal research spending in the U.S., as well as coercive measures targeting specific universities and researchers investigating climate science, vaccines and minority and gender issues, the commissioner said the bloc was in a unique position to serve as a refuge for top scientists. She also set out a trove of enticements for researchers hit by Trump’s moves. To enhance Europe’s “pull factor” for top-level talent, Zaharieva said the Commission would enshrine freedom of scientific research within EU law and immediately increase the financial support offered by the European Research Council (ERC), the bloc’s public body for scientific and technological enquiry. Most of the applicants to the Safe Space for Science scheme are researching subjects like climate change, immunology and infectious diseases, or social sciences involving gender, diversity and migration. | Scott Olson/Getty Images Currently, researchers based in the U.S. who relocate to Europe can apply for €1 million beyond the usual maximum grant amount, which will be increased to €2 million. That means, in total, these researchers could be eligible for grants of up to €4.5 million. ERC President Maria Leptin told POLITICO the body wants to maintain “Europe’s tradition of openness and support for independent, investigator-driven research, regardless of the nationality or the current location of grant applicants.”  Leptin insisted the ERC isn’t purposely trying to poach U.S. talent, “but we want to help our colleagues over there if we can.”  Citing a letter from 13 member countries urging Brussels to devise a strategy to nab U.S. researchers, Zaharieva said the Commission is working on a special visa for top talent, as well as a system to help governments and universities in the bloc pool resources to attract American scholars. A meeting will also be held to coordinate those actions with EU countries. “Europe has a historical responsibility to defend academic freedom,” the commissioner added, alluding to the persecution of scholars under Nazi and fascist regimes on the continent during the 1930s and 1940s. “Without freedom, knowledge cannot truly grow.”  OPEN DOORS, OPEN LABS Some universities have been quick to spot the opportunity, launching targeted recruitment schemes for U.S. talent. Last month, Provence’s Aix Marseille University (AMU) made headlines on both sides of the Atlantic by unveiling the Safe Space for Science scheme, a $16 million initiative to recruit up to 15 U.S. scientists whose research is being “threatened or hindered” by the new administration.  AMU President Eric Berton told POLITICO that the program — which was “born of indignation at what is happening to our American colleagues” — had been inundated with applications from nearly 150 researchers hailing from top universities including Yale, Colombia and Stanford, as well as from U.S. government agencies like the National Institutes of Health, the National Oceanic and Atmospheric Administration, and NASA.  Most of the applicants are researching subjects like climate change, immunology and infectious diseases, or social sciences involving gender, diversity and migration — fields targeted by the Trump administration’s war on science and diversity, equity and inclusion (DEI) issues. Berton added that even historians had applied to the program.  In recent weeks, similar schemes have been rolled out at other universities. Belgium’s Vrije Universiteit Brussel (VUB) has allocated funds and launched a dedicated welcome center with visa information for postdoctoral scholars who are “victims of political and ideological interference” in the United States. In Sweden, the prestigious Karolinska Institute, famous for its work on medicines and infectious diseases, said it was increasing its ability to respond to queries on relocating to Sweden for opportunities — “which have already started to come in” — and was liaising with other universities about how best to support academic emigrés from the U.S. INTELLECTUAL GOLD RUSH European cities and regional and national governments are also scrambling to attract top talent that has, until now, usually flocked to prominent and better-financed research institutions on the other side of the Atlantic. Citing figures like physicists Albert Einstein and Lise Meitner, scientists wrote in an op-ed in Der Spiegel that Germany and Europe now have the opportunity to “reverse the brain drain.” | Keystone/Getty Images In a bid to reinforce Berlin’s status as “a location for international cutting-edge research in the fields of medicine and social sciences,” the city is setting up a special fund to attract researchers from the U.S. Meanwhile, Catalan President Salvador Illa this week unveiled a €30 million Catalonian Talent Bridge regional recruitment scheme, which will finance posts for 78 American researchers in local universities and high-tech research institutions like the Barcelona Supercomputing Center and the National Centre for Genome Analysis.  Prominent scholars are demanding that national governments mobilize funds as well. Eight senior scientists and professors in Germany published an op-ed in Der Spiegel this week urging the country’s leaders to target “100 bright minds for Germany” in a concerted recruitment drive. Citing figures like physicists Albert Einstein and Lise Meitner — both of whom emigrated to escape Nazi persecution during the Third Reich — the scientists wrote that Germany and Europe now have the opportunity to “reverse the brain drain” of the past and “not only strengthen our own innovation and research power, but also cushion the global loss of knowledge progress.” Despite steep budget cuts in the Netherlands, Minister of Education, Culture and Science Eppo Bruins recently told lawmakers the country would prioritize allocating funds to recruit international scientists that are “worth gold to Europe and the Netherlands.” Spain is already using Atrae, a scheme originally launched to help repatriate high-level Spanish scientists who had emigrated for economic reasons, to court American scholars. Similarly, Belgium’s established Brains for Brussels program — which finances foreign scholars researching artificial intelligence, IVF and other fields that are financially relevant for Belgium’s capital region — is expected to be used to attract U.S. applicants this year. AMU President Berton said European academic institutions like his own would have “preferred not to have to launch” these initiatives, but that the talent they attract will help the bloc’s universities “develop new research and strengthen their activities.” Most importantly, he added, their presence on campuses on the continent will represent “a response from the Europe of knowledge to a form of obscurantism gaining ground in the United States.” Mari Eccles contributed reporting.

Greg Rossi, Senior VP, Head of Oncology Europe and Canada at AstraZeneca Despite many pioneering innovations in cancer in recent decades, across Europe, cancer-related deaths are still rising and health outcomes vary significantly. Politico Studios sat down with Greg Rossi, Senior VP, Head of Oncology Europe and Canada at AstraZeneca, to discuss the key issues and his vision for transforming cancer care. This is a critical point in European cancer care. What are the greatest challenges and how can they be overcome? First, we should recognize that there have been remarkable transformations in scientific understanding and cancer treatment in recent years. Many people with cancer around the world are living healthier, longer lives. > We can start to imagine a future where for many patients, cancer is no longer > a cause of death. However, the situation is far from where it needs to be to make this a reality, especially in Europe. Today, one in two people will be diagnosed with cancer in their lifetime, and roughly one in five people still die from it.1,2 In 2022, there were 1.3 million cancer-related deaths in Europe, which is projected to increase to 1.7 million by 2040.3 This burden is not felt equally. Five-year survival rates vary significantly between countries, for example, the rate is around 10% in Lithuania and over 20% in neighboring Latvia.4 Inequalities are also apparent within countries: an estimated 32% of cancer deaths are attributable to educational inequality,5 in addition to ethnic and gender disparities.6 We must celebrate that Europe is one of the world’s leading innovation hubs.7 Yet the crux of the issue is that patients wait too long to access potentially life-saving drugs; pressures are growing on already stretched healthcare systems and significant inequalities persist in cancer outcomes. As things stand, cancer will be the leading cause of death in the EU by 2035.8 This trajectory is not inevitable. The fundamental changes we need can only be achieved by working in partnership – research, technology or policies created in silo will not work. Health professionals, scientists, advocates, governments and patients must align and coalesce towards a bold but, I believe, achievable, mission for change. What are your priority areas? > We need a future-focused approach to defining optimal cancer care for the > coming decades while taking immediate, concrete steps to achieve change. I see four immediate pillars of opportunity to build on, underpinned by leveraging data and technology. Earlier detection and screening An essential first step is to detect cancers earlier. A 20-year follow up of the International Early Lung Cancer Action plan found that when lung cancer is detected at an early stage, up to approximately 80% of people live for ten years or more;9 the five-year survival rate drops to a mere 10% if the cancer is detected at a late stage.10 This pattern is mirrored in other cancers.11 Many European countries have already seen promising results from pilot screening programs for lung cancer – for example, the proportion of lung cancers found early has expanded from 29% to 76% in areas where a community-based lung cancer screening program was initiated in England.12 Currently, widespread implementation of lung cancer screening across Europe is slow and inconsistent. While many European countries have seen promising results from pilot programs, few are implementing them nationally. There is an opportunity for all national governments to fully implement the European Council Recommendation on Cancer Screening, offering national screening for breast, cervical, colorectal and lung cancer for everyone at high cancer risk.13 Timely and equitable access to diagnostics and treatment Pioneering advances in genomics and imaging have made it possible to characterize cancer based on genetic markers or individual risk profiles, making effective, personalized cancer care a reality for some patients. Tailored treatments can offer improved survival and quality of life while reducing exposure to potential side effects from more standard treatments. However, access to the diagnostic tools needed for personalized cancer care is not uniform across Europe. Significant disparities persist in access. In 2020, approximately 15% of people with lung cancer received personalized treatment in Portugal, dropping to 4% in the UK and 2.5% in Poland – against the European Society for Medical Oncology’s advised benchmark of 10%.14 In 2021, the European Medicines Agency had a lower percentage of new active substances approved via expedited reviews compared with the U.S. Food and Drugs Administration, Canada and Japan (9% vs 71%, 26% and 45% respectively).15 Across Europe, 52% of innovative cancer medicines are not publicly funded, and time to funding has increased since 2022, reaching over 1.5 years.16 To address this challenge and prepare health systems for the future, we need policymakers to recognize the importance of investing in technologies as part of integrated science, healthcare and industrial policy. EU Health Technology Assessments should minimize procedural burdens for member states, to ensure efficient, equal access to treatment. We must also work together as a community, building a skilled workforce with the expertise to implement these new technologies effectively, while growing public trust and understanding in them. Equitable access to clinical trials Clinical trials are vital to advance innovation and develop new treatments. We must ensure that the European environment promotes research – as recognized in the 2021 ACT EU initiative.17 Slow approval processes and conflicting application requirements between countries risk stifling innovation and undermining our common goal, which should always be to make Europe a patient-centered innovation hub. Currently, participation in clinical trials is particularly low among people from underserved communities in Europe. Ensuring that clinical trial participants represent the entire population is therefore an essential goal. Sustainable healthcare systems A bold, forward-looking vision for cancer care must involve strengthening health systems in their entirety. Sustainable healthcare involves a spectrum of resources, including workforce, technology, infrastructure and adoption of wider innovation. Cancer diagnoses in Europe are expected to increase by 21% from 2020 to 2040, while the healthcare workforce is expected to grow only 5%, potentially leading to a shortage of 4.1 million healthcare workers in Europe by 2030.18,19,20 Actively using artificial intelligence and digital technologies can help support cancer care professionals to deliver faster, more accurate and resource-efficient care, with new technologies and ways of working embedded into training. Work is also required to better integrate new technologies into patient care pathways, building on Europe’s growing network of comprehensive cancer centers. Despite the scale of the task, should we be hopeful cancer care will improve? > At AstraZeneca, our goal is to redefine cancer care. We believe that, one day, > we will eliminate cancer as a cause of death. This vision is shared by multiple stakeholders who are all working to improve cancer outcomes. However, achieving a goal of this magnitude will require collaboration across governments, health systems, researchers, patient groups and industry. It’s the right thing to do, it’s our duty of care. We hope that, by working together, we can make a transformative impact on what cancer means to future generations. -------------------------------------------------------------------------------- References 1. European Commission. Cancer in Europe: 5 things the data tells us. 2022. Available at: https://joint-research-centre.ec.europa.eu/jrc-news-and-updates/cancer-europe-5-things-data-tells-us-2022-01-13_en (accessed September 2024). 2. EuroStat. Cancer Statistics. 2024. Available at: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Cancer_statistics (accessed September 2024). 3. European Commission. Impact of Population Ageing on the Burden of Cancer up to 2024 in EU/EFTA Countries. Available at: https://ecis.jrc.ec.europa.eu/sites/default/files/2024-09/2024_08_Factsheet_2040CancerEstimates.pdf (accessed September 2024). 4. The Swedish Institute of Health Economics. Tackling inequalities in cancer care in the European Union. Available at: https://efpia.eu/media/cnygfywo/tackling-inequalities-in-cancer-care-in-the-european-union.pdf (accessed September 2024).  5. Vaccarella S, et al. Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study. Lancet Regional Health 2023;25:100551. 6. Van Poppel H, et al. European Cancer Organisation’s Inequalities Network: Putting Cancer Inequalities on the European Policy Map. JCO Glob Oncol 2022;8:e2200233. 7. World Intellectual Property Organization. Global Innovation Index 2023. Available at: https://www.wipo.int/edocs/pubdocs/en/wipo-pub-2000-2023-en-main-report-global-innovation-index-2023-16th-edition.pdf (accessed September 2024). 8. European Commission. Europe’s Beating Cancer Plan. Available at: https://health.ec.europa.eu/system/files/2022-02/eu_cancer-plan_en_0.pdf (accessed September 2024). 9. Henschke CI, et al. A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP). Radiology 2023;309:2. 10. The Health Policy Partnership. Powering the future of cancer care with advanced diagnostics. 2024. Available at: https://www.healthpolicypartnership.com/app/uploads/Powering-the-future-of-cancer-care-with-advanced-diagnostics_report.pdf (accessed September 2024). 11. UK Office of National Statistics. Which cancers would benefit most from earlier diagnosis? 2021. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/whichcancerswouldbenefitmostfromearlierdiagnosis/2019-06-18 (accessed September 2024). 12. UK Government. New lung cancer screening roll out to detect cancer sooner. 2023. Available at: https://www.gov.uk/government/news/new-lung-cancer-screening-roll-out-to-detect-cancer-sooner (accessed September 2024). 13. European Commission. Cancer Screening Recommendation – update. 2022. Available at: https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/13155-Cancer-Screening-Recommendation-update_en (accessed September 2024). 14. Hofmarcher T, et al. Systemic anti-cancer therapy patterns in advanced non-small cell lung cancer in Europe. J Cancer Policy 2022;34:100362. 15. EFPIA. Why Europe must future-proof its pharma legislation. 2023. Available at: https://www.efpia.eu/news-events/the-efpia-view/blog-articles/why-europe-must-future-proof-its-pharma-regulation/ (accessed September 2024. 16. EFPIA. Patients W.A.I.T. Indicator survey 2022. Available at: https://efpia.eu/media/vtapbere/efpia-patient-wait-indicator-2024.pdf (Accessed September 2024). 17. European Medicines Agency. Accelerating Clinical Trials in the EU (ACT EU). Available at: https://www.ema.europa.eu/en/news/accelerating-clinical-trials-eu-act-eu-better-clinical-trials-address-patients-needs (accessed September 2024). 18. European Commission. European Cancer Information System: 21% increase in new cancer cases by 2040. 2022. Available at: https://joint-research-centre.ec.europa.eu/jrc-news-and-updates/european-cancer-information-system-21-increase-new-cancer-cases-2040-2022-03-16_en (accessed September 2024). 19. Vintura. Addressing urgent workforce shortages. 2023. Available at: https://www.efpia.eu/media/qdknvwve/addressing-urgent-workforce-shortages.pdf (accessed September 2024). 20. Michel J-P & Ecarnot F. The shortage of skilled workers in Europe: its impact on geriatric medicine. Eur Geriatric Med 2020;11:345–7. -------------------------------------------------------------------------------- Veeva ID: Z4-68574 Date of Preparation: September 2024

As the European Union embarks on a new political term, the importance of having robust capacity to respond to the needs of vulnerable populations and public health challenges cannot be overstated. Recently, the European Court of Auditors’ report underscored the need for improvements in internal organization, procedures, systems and publications within EU health agencies, including the European Centre for Disease Prevention and Control (ECDC). We, at Sanofi, experienced this first-hand with a recent ECDC assessment report that overlooked the scientific standards built over decades, lowering the bar for assessing the benefit/risk of vaccines and creating a precedent with damaging consequences for both public health and Europe’s thriving life sciences sector. We believe this example highlights some weaknesses and provides concrete opportunities for upholding transparency and modernizing our European health assessment system. A recent case study Regulatory agencies and public health agencies like the ECDC evaluate and document the benefit and risk of medicines and vaccines supporting their use. Although the systems are not fully harmonized across the globe, the strength of the evidence is graded because different types of trials offer different levels of certainty about benefit and risk. For decades, randomized controlled trials (RCTs) have been considered the gold standard in medicine. The robustness of RCTs comes from the i) random allocation of volunteers to the treatment or control arm and ii) strict adherence to pre-determined endpoints and statistical plan. These two characteristics, combined with the large size of phase 3 RCTs, considerably reduce the risk of bias and provide the best estimate of a vaccine’s or medicine’s performance. Observational studies, where case and matched controls are selected a posteriori or based on known facts, also offer a view on a product performance but with lower confidence than an RCT. The danger of concluding on the benefit of a product based on observational trials was exemplified during the Covid-19 pandemic, when initial observational studies suggested that ivermectin and hydroxychloroquine were effective in preventing Covid-19 until rigorous RCTs proved unequivocally that this was not the case.  > The danger of concluding on the benefit of a product based on observational > trials was exemplified during the Covid-19 pandemic, when initial > observational studies suggested that ivermectin and hydroxychloroquine were > effective in preventing Covid-19 until rigorous RCTs proved unequivocally that > this was not the case. In our example of a recent review on the efficacy of newer influenza vaccines, the ECDC considered that an opaquely reported 512 participant, observational study was of an equivalent strength of evidence as a transparently reported, 31,989 participant, gold standard randomized controlled trial (RCT) using the data of two flu seasons.1 The former 512 participant trial was based on a subset of a larger study and utilized a modified, statistical analysis that favored the treatment group over control. This resulted in lifting the negative unadjusted relative vaccine efficacy of -92% to an adjusted relative vaccine efficacy of +59%.2,3 This naturally raises questions about the validity of the study, and how the ECDC could equate this study to an RCT. We are not the only ones questioning the rigor and validity of this report, which sparked controversy within the scientific community. Physicians and scientific experts are questioning the quality and transparency of the evidence the ECDC used to underpin its recommendation. Public health and investment in medical innovation are at stake Flu does more damage than most people realize. It can lead to severe complications, increasing the risk of heart attack and pneumonia. Flu also puts a considerable strain on already stretched healthcare systems across Europe during the winter season. We believe that the ECDC equating the validity of observational and RCT trial findings at a time when we need to build trust in vaccines is a retrograde step that may place vulnerable people at greater risk of hospitalization.  Moreover, there is a possibility of a domino effect that destabilizes future investment in therapeutic innovations backed by the highest standards of scientific rigor and transparency. What incentive is there for the life sciences industry to keep investing in expensive RCTs if health agency recommendations signal that the gold standard is no longer necessary? Author: Pedro Castellano > What incentive is there for the life sciences industry to keep investing in > expensive RCTs if health agency recommendations signal that the gold standard > is no longer necessary?  A constructive call to action The ECDC’s advice is central to supporting European health systems. As sciences and technologies keep evolving at lightning speed, increasingly rigorous frameworks are required to support product assessment. Mistakes and judgment errors can happen even under the most robust processes. In our experience, appropriate checks and balances and a mechanism for appeal and revision of inaccurate assessment is lacking in the ECDC’s processes. Creating one would undoubtedly uphold transparency and ensure that the highest standards are applied when establishing recommendations for the benefit of EU citizens.   The upcoming hearings of designated Commissioners are an ideal time to advocate for a plan to enhance the scientific rigor of EU health assessments and better coordinate among EU health institutions. By upholding the principles of scientific integrity, we can protect the incentives to invest in innovative health solutions, strengthen public trust in vaccines and medicines, bolster public health system resilience, and ultimately save lives. -------------------------------------------------------------------------------- References [1] European Centre for Disease Prevention and Control. Systematic review of the efficacy, effectiveness and safety of newer and enhanced seasonal influenza vaccines for the prevention of laboratory confirmed influenza in individuals aged 18 years and over. Stockholm: ECDC; 2024. [2] Domnich A, Panatto D, Pariani E, Napoli C, Chironna M, Manini I, et al. Int J Infect Dis. 2022; 125 (Dec.): 164-169 DOI: 10.1016/j.ijid.2022.10.041. [3] Domnich A. Int J Infect Dis, 145 (2024), 107104 https://doi.org/10.1016/j.ijid.2024.107104