Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

Peter O'Donnell

There is some powerful support for personalized and precision medicine in the 'Porto declaration on cancer research' that was opened for signature on May 3

 in the Portuguese city famed for its more traditional approaches to a sensation of well-being. The occasion was the EU Cancer Research Summit, where the accent was on developing a network of well-distributed and interconnected high-quality infrastructures for translational research, clinical and prevention trials, and outcomes research.

In particular, it recommends action across three specific areas of research: translational, clinical, and outcomes. European-wide deployment of high-quality infrastructure could achieve a 10-year cancer-specific survival for 75% of patients diagnosed in EU member states by 2030—a literally vital contribution in the face of an expected increase of cases in EU from the current 3.5 million to more than 4.3 million by 2035.

With successful proof of principle clinical/prevention trials, translation will continue by means of clinical research to achieve effective healthcare system implementation, at the same time reducing the timespan from scientific discovery to patient benefit, says the declaration. But complex and advanced infrastructures are required to make the bridge to healthcare from basic/preclinical research and clinical and prevention research, building on inventions and innovations from basic/preclinical research to directly impact therapeutic and prevention research. The use of molecular and digital pathology for stratifying patients for systemic treatment with anticancer agents is increasing and liquid biopsies are being implemented as a complementary diagnostic/monitoring tool, and infrastructure support is also increasing in complexity for radiation and surgical therapy, imaging, and immunotherapy. But consortia of advanced cancer care centres are required to make the necessary links.

Infrastructures for clinical and prevention trials can take 'proof-of-concept’ studies as a starting point for further clinical and prevention research, with a practice-changing aim, including the assessment of its utility in healthcare or prevention, patients and individuals at risk, cure and survival, and health-related quality of life. But it will require well-developed clinical trial structures, and advanced diagnostic methods such as state-of-the-art molecular pathology, omics technologies, and pharmacology, as well as innovative imaging, to stratify patients are crucial.

Prevention will depend on infrastructures that include strong epidemiology closely connected to basic research, data acquisition capacity, and advanced computational capabilities, Appropriate funding mechanisms are needed to stimulate these activities and guarantee sustainability, including for proof-of-concept trials initiated by academic investigators, says the declaration.

Infrastructures for outcomes research will make it possible to deliver on the assessment of clinical utility, cost-effectiveness, accessibility, sustainability, and prioritization. Outcomes research in therapeutics must address all aspects of the clinical pathway, including treatment optimization, side effects of treatments, long-term follow-up with assessment of health-related quality of life, rehabilitation, and survivorship, as well as attention to social and economic aspects, and should be a collaborative effort between clinicians, researchers, and epidemiologists.

"Precision oncology isn't only about what is new. It's also about making better use of what we already have," Denis Lacombe, director general of the European Organisation for Research into and Treatment of Cancer, told the Porto conference to launch the declaration. He cited EORTC's SPECTA infrastructure for access to personalized medicine clinical research programs as an example of a successful quality assured clinical trial’s structure, arguing in favour of harmonisation of technical requirements to support multinational collaborations in next-generation clinical trials. "Current regulatory and research approaches leave many areas of treatment knowledge under addressed," he said, pointing to issues of dosage, sequence, combination, or possibilities of de-escalation.

He insisted that society will have to develop the means to generate datasets aiming at documenting the optimal treatment for cancer patients though the integration of clinical research, free of commercial interest in the process of access to treatments, and to inform healthcare systems. This means that for optimized treatments in healthcare, society must re-engineer new models of partnership between commercial and non-commercial research in the continuum of clinical science, regulatory science, and into health technology assessment. Public health priorities will need to command upstream research, to focus innovation where needed, and avoid multiplication of redundant agents of the same class.

While the needs were great, not everything needed creating de novo, he argued, "Europe should build on existing solutions and infrastructures which deliver, optimizing competences and avoiding duplication."

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The EU Cancer Research Summit sparked powerful support for personalized and precision medicine across three specific areas of research: translational, clinical, and outcomes.

Exploiting Research Infrastructures for Personalized Medicine in Europe

Pressure is mounting in Brussels for the creation of new structures to debate pharmaceutical policy—with the drug industry making most of the running. It's a critical moment in Europe for policy formation on healthcare (although COVID has made that observation true for practically everywhere in the world). The drivers in Europe are not just COVID, but a growing sense among many actors in the healthcare world that longstanding divisions amongst them are inhibiting the sort of improvements that European citizens are entitled to expect.

At official level, the European Union has already acknowledged the need for some closer alignment between its distinct but overlapping institutions, with the emergence of declarations of intent to create a European Health Union and promises of a radical review of EU rules on pharmaceuticals—all predating the arrival of COVID's additional impact of concentrating minds. In concrete terms, the most visible new official moves so far are the structures created for joint procurement of supplies of COVID vaccines, and new links between the European Medicines Agency and the European Centre for Disease Control for combating drug shortages. But there is support within the European Parliament and the European Commission for more ambitious official EU engagement in health policy and a corresponding extension of EU competences into traditionally national government territory—although as a telling demonstration of the sort of divisions that dominate Europe, this is viewed by many of the member states in the EU's Council with extreme caution and has even provoked some downright resistance.

But the pressures come from other actors too. A broad-based grouping, the self-styled EU Health Coalition, has entered the fray with a call for "a permanent multi-stakeholder forum for better access to health innovation." This is needed, it says, to "contribute to guaranteeing more equitable access to health innovations for all European citizens and patients." The group's make-up is an interesting mix: medical specialty organizations, rare disease support groups, patient federations, biobanks, the Wellcome Trust - and a phalanx of industry associations representing manufacturers and wholesalers of medicines and medical devices.

The agenda of this impressive line-up is also an interesting mix. According to its just-released manifesto, collaboration is needed between European policymakers, member states, and all other actors across the health community—and even more so in the wake of COVID. But the aims range from leveraging the latest scientific advances and positioning Europe "as a hub for innovation in health" with "a well-functioning research ecosystem" to recognizing "the right of everyone to timely access" to affordable care, tackling health inequalities, and responding to the widely differing health status of citizens across the economic divides of west and east Europe.

These goals are not, of course, mutually exclusive, or even—in principle, at any rate—antithetical. But their enunciation slides somewhat glibly over the underlying tensions that condition these issues in Europe. There is a suggestion among all the rhetoric that somehow all the problems will be solved if only new drugs and devices get faster market access. The distinctively pro-industry tone—"access to medical innovation and new digital technologies is very patchy across EU countries", with the blame laid largely at the door of "reimbursement processes whether national or regional"—is an odd match with the references to low life expectancy in Bulgaria or challenges in providing care to populations discriminated against by gender or ethnicity.

The strongly pro-industry messaging was reinforced when the head of the main European drug industry federation praised the manifesto during a multi-stakeholder conference on access to medicines at the end of April. "As an industry we have no doubt that it is only through jointly analyzing and addressing barriers to access, availability and affordability of medicines that we will reach successful and sustainable solutions for today and tomorrow’s patients," said Nathalie Moll, the director general of EFPIA—and a prime mover in the formation of the coalition. "This is why we strongly support the call of the EU Health Coalition to the Portuguese Presidency ahead of today’s event for the set-up of an EU Forum for Better Access to Health Innovation, a paramount steppingstone towards the achievement of the shared goal of equal access to innovation across the EU," she added.

Other healthcare actors in Europe who are not members of the EU Health Coalition have taken a different view—ranging from the most radical, who accuse the drug industry of ruthlessly exploiting powerful monopoly positions to lobby for profit, to respected politicians and officials who urge a healthcare approach that focuses more on prevention and health promotion than on treatment. Healthcare payers such as the mutual insurance association AIM, with a focus on patients rather than on healthcare providers, are actively seeking to build coalitions of other like-minded players, while groupings of national healthcare agencies—often incorporating patients and consumers in their deliberations on healthcare strategy—have refused to admit industry representatives.

This is not to argue against the principle of seeking better understanding between groups with—often—diametrically opposed interests. No-one would deny that Europe's healthcare provision is perfectible—to say the least. And the better solutions to the complex problems of healthcare are always going to come from seeing the bigger picture together rather than from trench warfare among hostile groups. But the process will be more constructive if it is based on precision and clarity and candor in forming groups and setting agendas—without which the prospects for better understanding are reduced rather than increased.

Pressure mounts in Brussels as calls for new ways to debate pharma policies come from all directions

New Structures to Tackle New Challenges in European Healthcare

The European Parliament's health committee is hammering home some of the lessons from the COVID pandemic, which demonstrated so clearly that Europe, both at EU level and among its 27 member countries, "was not ready to deal with public health emergencies." In an April 15 debate, MEPs restated—yet again—the need for changes to the way the EU operates in terms of health policy. Not the first such demand, but the latest in what is becoming a tidal wave of calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

"Despite having experienced previous threats, health structures were not geared towards this possibility," said Spanish socialist Nicolas González Casares, who is leading the parliament's examination of EU plans for upgrading the role of the European Medicines Agency in the wake of the devastation wrought by the pandemic. He attributed the inadequacy to budget cuts that have "diminished the adaptive capacities of our health systems," and pointed to the desperate attempts to cope over the last year as the European Commission and EMA "have had to act by setting up ad hoc structures to achieve a better and more coordinated response."

He told his fellow MEPs that "there is a need for the Union to equip itself with an appropriate institutional framework to deal with emergencies such as the one we are experiencing, without having to improvise, with a clear mandate, and by providing a legal framework for EU institutions to play a more active role." And first up is the proposal for a strengthened mandate of EMA. However, the principal objective of his plea is not to arrange for faster authorization of new medicines to tackle pandemics, not to offer incentives to innovate. Instead, this proposal is limited to bolting additional tasks onto EMA in relation to the specific issue of drug supplies. His draft recommendation is designed to avert the sort of penury in medicines that have hit health services since the crisis began, and he urges developing an institutional framework that defines who does what at any given moment, provides for monitoring and controlling the medicines supply chain, and an agreed definition of drug shortages. He wants to see steering groups set up to overview the production and supply chain for medicines and medical devices. He spoke at length on the need to coordinate and share the knowledge among the member states, the EU institutions and the pharmaceutical industry, and on the merits of creating a European medicines supply database.

"Had a regulation of this nature been in force before the pandemic, some issues such as shortages or the approval of new treatments would probably have been dealt with more deftly during the pandemic," remarked González Casares. He may be right. But readers of ACT will be relieved to be reassured that the EU response to COVID goes further than merely turning EMA into a pill-counting institution. As González Casares acknowledges in the document, he presented to the health committee, there are other EU initiatives underway of a more strategic nature. Another of these was debated and voted through by the committee on April 16: a new procedure to accelerate the EU-wide approval of vaccines adapted to COVID variants. This takes the form of a rapidly-created legal provision to ease the passage of vital new medicines through the EMA's authorization system. It will provide a simplified procedure for vaccines that have already received EU authorization but which are being adapted to be effective against variants of the virus.

Their vote—which now needs to be endorsed by the parliament as a whole at a future plenary session—comes after the release of an EMA reflection paper in February, and discussions in recent weeks with senior members of EMA, including Marco Cavaleri, head of its office on biological health threats and vaccine strategy. They received assurances on the criteria and operation of the new mechanism—including requirements that variant vaccines must be based on already approved/in use vaccines, and justification for the relevance of the variants included, based on disease surveillance and characterization of strains circulating at the time of selecting the variants. The efficacy of a monovalent or a multivalent variant vaccine against the variant strains may be inferred from provision of immunogenicity data after primary vaccination with the variant vaccine; and after a single dose of the variant vaccine when given to subjects who previously received primary vaccination with the parent vaccine. And as soon as a global forum is established to support SARS-CoV-2 strain selection for vaccines (such as has been discussed at the World Health Organization), the recommendations made should be consulted when selecting the variant strains.

This may prove a more effective measure to bring the pandemic under control—but it also underlines the growing conviction among many Europeans—and their politicians—that there is a need for more Europe in the field of health, and for progress towards a health union to match the EU's other major achievements such as its monetary union that created the Euro and its customs union that permits free trade across the internal borders between its member states.

Parliament's health committee is answering calls for a firmer grip on policies affecting the well-being of its 450 million citizens.

Dragging the EU into a More Health-Conscious Post-COVID Dynamic 

Precaution continues to dominate EU thinking on science and technology–with politics intervening to offer some intriguing impacts on human health. Amid the heated COVID-driven controversies over vaccination that are ruffling Europe, a specialized European advisory group on ethics has just issued a cautious opinion on the use of gene editing–including a call for a global guarantee that heritable human genome editing is not prematurely clinically applied. In addition to the intrinsic interest of the subject and of the opinion the group presents, the views it expresses offer an interesting comparison to–or contrast with–the apparently haphazard decisions by EU countries over recent weeks in respect of the AstraZeneca vaccine against COVID.

The European Group on Ethics in Science and New Technologies (EGE) is tasked with advising the European Commission with “high quality, independent advice on all aspects of EU legislation and policies, where ethical, societal and fundamental rights issues intersect with the development of science and new technologies.” In a 

new and broad-ranging opinion on genome editing

, the group urges a degree of caution–notably that this technology should not be applied “for purposes other than against serious diseases that cannot be prevented or treated otherwise.” And it stresses the need for safeguards against enhancement or de-enhancement of traits, and to ensure that investments in research on germline genome editing have the purpose of protecting health. But at the same time, the opinion acknowledges that somatic genome editing has the potential to alleviate suffering from diseases that could not be treated effectively before, and recommends pursuing its use, along with providing access to clinical studies and clinical application in healthcare.

Particularly striking is the treatment of expertise in the opinion. This, it says, is vital to “ensure adequate competencies in expert bodies.” As it observes, genome editing technologies are evolving quickly and expertise to assess research and application has to keep pace with new developments, so it is important to widen the basis of expertise and broaden what counts as relevant knowledge at the level of expert committees, fora and other bodies established to examine and set guidelines and standards for research and application of genome editing technologies. It extends the advice to providing due guidance for ethics committees charged with approving and supervising clinical trials involving genome editing, covering safety assessments and risk/benefit determinations of clinical trials are developed, along with training modules for research ethics committees and other involved bodies “to ensure high-standing and consistent application of ethical standards.”

With a view to promoting broad alignment, the group has asked the European Commission to engage in global discussions on regulation of this emerging field with the World Health Organization and the World Medical Association, covering universal adoption of standards on the ethical use of genome editing in human beings. And within Europe it wants to see the creation of a specifically European platform to exchange information and promote “a broad and open public debate” on the ethical and social implications of germline genome editing in human beings. It stresses that this will require a “basis of sound and evidence-based information,” and a heightened awareness of the implications of widely used terminologies and distinctions such as somatic and germline editing, or prevention, therapy and enhancement.

What might the group have said if it had been asked to give an opinion on the EU’s recent performance in the use of vaccines–and specifically, the AstraZeneca vaccine? Not the squabbles between the UK and the EU (and even within the EU!) on delivery, which are almost too unseemly to merit attention here, but on the more sensitive area of efficacy and safety judgments concerning innovations. From the outset, there was disunity among the member states about whether, in the absence of trial data from the elderly, the vaccine should be given to older people–with France, notably, withholding it from those over 75 years of age. But then anecdotal reports of blood abnormalities among a handful of recipients sent national authorities in the EU into paroxysms of incoherent indecision, destroying any semblance of EU alignment on evidence-based decision-making, as some countries suspended use of the product pending the outcome of a European Medicines Agency (EMA) review of the case reports, others imposed some limitations relating to age, and others carried on with administration regardless. And when EMA delivered an interim clearance of the product, many countries still refused to use it.

The picture was of politics replacing evidence-based decision-making, as governments responded to public (and often ill-informed) anxiety rather than to scientific evaluation. The summit of incoherence was reached when member states subsequently reverted to following expert advice: governments that had ignored the advice of the EMA and suspended the use of the AstraZeneca vaccine then reinstated its use–in line with the advice from the same institution. It was another example of action driven by a European tendency to bow to uninformed public opinion, playing safe politically rather than scientifically. It epitomized a question that has assumed growing importance over the last 50 years: how to take account of public sentiment while science itself evolves. The exploitation of gene technology in food and agriculture from the 1980s has manifestly been impaired in Europe by public concerns, not always on the basis of a good understanding of the subject. A similar cloud already hangs over the development of nanotechnology. The debates have often not been edifying, since they have frequently relied on acute emotion rather than on accurate information. And the risks from widespread misinformation and even from conspiracy-driven dis-information are currently crystallizing conspicuously in vaccine hesitancy and frank anti-vaccination movements, frequently linked to the relative novelty of
mRNA vaccines.

The disarray among national governments in Europe will have done nothing to inspire confidence either in science in general, or in Europe’s regulatory institutions–and least of all, confidence in vaccines. Governments’ knee-jerk responses to lurid headlines, with the principal aim of avoiding blame if things go wrong, do not constitute a noble strategy in times of crisis. Defensive appeals to that “precautionary principle” beloved of many European policymakers are not necessarily the right approach to public debate on the relative risks and benefits of alternative courses of action. The advice of the EGE about ensuring “a broad and open public debate” on the “basis of sound and evidence-based information” might be a better guide. And above all, for those utterly obsessed with the precautionary principle, it should have been evident that seeking to protect the public from a minimal risk of vaccine side effects would in any case expose people to an even greater risk–of contracting a serious disease that has already killed hundreds of thousands across Europe.

 is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium

European Group on Ethics in Science and New Technologies issues cautious opinion on the use of gene editing amidst COVID vaccination controversy.

Peter O'Donnell

Articles

Exploiting Research Infrastructures for Personalized Medicine in Europe

New Structures to Tackle New Challenges in European Healthcare

Dragging the EU into a More Health-Conscious Post-COVID Dynamic

Europe's Eternal Struggle with Safety and Innovation