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.
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?
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
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