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

Peter O'Donnell

The European Union is still beating itself up for its failings in countering COVID, and the latest initiative to emerge in its bid to remedy the deficiencies is destined to make some early changes to the rules on medicines marketing, and to bring in some longer-term changes to clinical development too. The project, known as HERA—a classic EU non-abbreviation, this time for the European Health Emergency Preparedness and Response Authority—is now taking shape, with multiple objectives that will overall, according to the European Commission proposal, be a systematic response to "revealed vulnerabilities in global supply chains, and insufficient oversight of manufacturing capacities and research priorities in the EU."

EU leaders have been calling for urgent action, ranging from better epidemiological data to mobilizing research funds, and for regulatory flexibilities to accelerate the development of vaccines and therapies, as well as more joint procurement programs for critical supplies. They have openly acknowledged their admiration for the example shown by the US Biomedical Advanced Research and Development Authority in accelerating the development of countermeasures and boosting manufacturing capacities when needed.

So, HERA is going to come into being, as a complement to the European Center for Disease Prevention and Control and the European Medicines Agency. And in the meantime, a series of immediate actions "will test a number of solutions that could serve as a blueprint"—looking particularly at emerging biological threats to human health and antimicrobial resistance. One of these is the 'HERA incubator', presented as a concept in mid-February. This will provide new money for genomic testing, more agile approval procedures, and pressure for industry to boost production capacity. Sourcing vaccines from beyond the EU and support for transfer of technology are also entertained as options.

One of the first changes likely to take effect will be faster regulatory processing of vaccines adapted to tackle COVID variants. Based on current EU procedures for approving annual influenza vaccines, it will permit release on a smaller set of additional data submitted to the European Medicines Agency on a rolling basis, with early guidance for developers on data requirements. Central to this approach is a "new category of emergency authorization of vaccines at EU level with shared liability among member states". The real novelty is the sharing of liability. At present, member states can give deliver national-level emergency approvals on the basis of only limited data—as Hungary has done for the Russian Sputnik vaccine—but each country that chooses this route must cover any liabilities that arise from the product's use. By giving such approvals formal EU status, the liability would be borne by all member states—which would, it is calculated, allow more rapid EU-wide response. To further ease supply, certification of new or repurposed manufacturing sites for vaccines will be pushed through faster, with early involvement of regulatory authorities.

Early responses to the EU thinking have been broadly favorable from stakeholders directly involved in drug development or regulation. The European affairs department of the French government has lent its support to the project, and the Danish government gave its backing, although with a warning against uncertainties arising from overlapping tasks—a view echoed by the German Medicines Manufacturers‘ Association, BAH.

Johnson & Johnson rapidly welcomed the proposal, urging large-scale investments in research and development for new vaccines, therapeutics, diagnostics and devices. "HERA should be equipped to collaborate throughout the entire process for the discovery, development, production, and deployment of effective countermeasures for future health crises, including pre-clinical and clinical development, manufacturing scale-up and validation, regulatory interactions and submissions, procurement and potential stockpiling," it said. GSK said it was ready to cooperate, via its network of 14 manufacturing and four R&D facilities across the EU and applauded the concept of a streamlined approach to development. It recommended funding HERA to carry out R&D and clinical development projects with appropriate research, industry and regulatory experts on its staff. EUCOPE, the lobby for Europe's smaller research-based drug firms, threw its weight behind closer coordination and cooperation, particularly for greater regulatory flexibility, and for the development and manufacturing of specialized medicines and vaccines for that are not viable without financial securities and regulatory collaboration.

In a detailed response, the main European drug industry association, EFPIA—together with its specialist Vaccines Europe section–endorsed the need for "a robust, resilient and agile ecosystem to anticipate and effectively manage pandemics and their consequences," and welcomed the ambition to create HERA. "What is needed most for effective emergency preparedness and response is a system that is connected, responsive and collaborative, as innovation and opportunities to address health threats may come from unexpected areas," it said. HERA could be both a central actor and a systems designer, working with health authorities and the private sector, it suggested. That will need "clear structures to address the existing gaps in supporting late-stage development and manufacturing." But it warns of the risk that such a complex structure "implies hurdles, which might reduce the speed of decision-making," so tools will be required "to eliminate redundant bureaucratic procedures and guarantee the necessary flexibility and speed to act." At the same time, the new authority should have strong ties with international agencies such as WHO or BARDA, to avoiding unnecessary competition and overlaps.

The process of creating this new agency is not going to run rapidly, since the EU has its own lengthy consultative and legislative machinery that must be satisfied. But just at the end of February, EU leaders gave a renewed jolt to the reflections, devoting an entire day of one of their summit meetings to beefing up Europe's response to COVID. EU Council President Charles Michel's invitation letter to the heads of state and government of the 27 member countries was unambiguous about the urgency: the situation "remains challenging due to the emergence of new variants," but "our priority continues to be to speed up vaccinations across the EU." Central to the discussions, he insisted, would be the issues around "accelerating the authorization process of vaccines, as well as their production and delivery," and "solutions to bring manufacturers across supply chains together in order to scale-up production in the EU."

It won't be the first time that EU leaders have been asked to act rapidly on an issue of crucial importance for Europe and its citizens—and their record has not always been perfect in coming up with the required responses. But this is the first time they have been asked to move fast against the background of a mounting toll of death and disease that their actions could prove to be literally vital in arresting.

Articles

The latest initiative against COVID, the European Health Emergency Preparedness and Response Authority, is taking shape with intentions of revealing the vulnerabilities in global supply chains and more.

Europe's Leaders Still Discussing How to Respond to the COVID Pandemic

The pressure is on for decisions over health technology assessment in Europe. After three years, the 27 member states of the European Union have still made no real progress on legislation that would coordinate their clinical assessments more closely, and meanwhile the two-decade-long trial of EU-funded voluntary cooperation among health technology bodies across Europe is on the brink of running out of time to demonstrate technical fixes to the duplication that some 80 independent national and regional HTA agencies are currently responsible for.

There is no timetable for member states to agree on the European Commission's 2018 proposal for working more closely together, and the arguments between them over whether it should be obligatory are still paralyzing progress. Eventually, if no compromise is reached, the draft law may just wither and die. And if the compromise reached does not satisfy the Commission as sufficiently robust in reducing duplication, the Commission may just kill the proposal off itself.

As for EUnetHTA, running on borrowed time since last year (it was due to finish its work in 2020, and the Commission extended its mandate and funding for one last year in the hope of progress), it still has a lot of work to complete. A cursory glance at its own programming demonstrates just how much.

One of EUnetHTA's objectives is to support the implementation of a HTA cooperation mechanism, and so far, there is no mechanism to support. It is also supposed to promote re-use of jointly-produced HTA reports—which is just what member states are currently squabbling over. Another is to "refine the production processes of joint assessment reports" and "facilitate the implementation of the joint assessment in national and regional practice." And yet another is to provide input on final processes and recommendations for a sustainable model of European collaboration on joint assessments after 2020—precisely what is not yet agreed by member states. Other aims are to provide manuals and methodological guidelines and fee structures and data requirements for the new system—which doesn't yet exist and doesn't look like it is going to anytime soon.

The recorded achievements of EUNetHTA consist mainly of winning approval for reports on some of the challenges encountered in tackling these issues or issuing recommendations for a system that has yet to be agreed on, much less built, or organizing meetings among "stakeholders"—many of whom appear unwilling to make any progress.

At least one positive step has however been made towards a common approach on HTA—a definition of HTA itself has been agreed. But this step has been taken at global rather than European level, with EUnetHTA just one of the participants. An international task force of the major HTA organizations has reached consensus after a three-year consultation. The definition is short but represents a lot of long discussion.

"HTA is a multidisciplinary process," it says, "that uses explicit methods to determine the value of a health technology at different points in its lifecycle. The purpose is to inform decision-making in order to promote an equitable, efficient, and high-quality health system." It is accompanied by four short notes, one of which defines terms: "A health technology is an intervention developed to prevent, diagnose or treat medical conditions; promote health; provide rehabilitation; or organize healthcare delivery. The intervention can be a test, device, medicine, vaccine, procedure, program, or system." Another describes the process: "The process is formal, systematic, and transparent, and uses state-of-the-art methods to consider the best available evidence." Another considers methodologies: "The dimensions of value for a health technology may be assessed by examining the intended and unintended consequences of using a health technology compared to existing alternatives." These dimensions, it adds, "often include clinical effectiveness, safety, costs and economic implications, ethical, social, cultural and legal issues, organizational and environmental aspects, as well as wider implications for the patient, relatives, caregivers, and the population. "The overall value may vary depending on the perspective taken, the stakeholders involved, and the decision context." A fourth note makes clear that HTA "can be applied at different points in the lifecycle of a health technology, that is, pre-market, during market approval, post-market, through to the disinvestment of a health technology."

The process involved wide consultation with the broad HTA community. It was co-led by the International Network of Agencies for Health Technology Assessment and Health Technology Assessment International, with active participation from the regional HTA networks in Asia (HTAsiaLink) and the Americas (RedETSA), along with EUnetHTA. The International Society for Pharmacoeconomics and Outcomes Research and the World Health Organization took part as observers, and the final version has also been approved by the EuroScan International Network. For all the discussions of HTA over the last half-century, and all the guidelines and procedural manuals developed at national and regional level, there has not been a global consensus on the definition until now. For the instigators of this initiative, the success is a "historic achievement" that reflects "the maturity of the international HTA community to come together for a common purpose."

After three years, member states of the EU have yet to make any real progress on legislation that would coordinate their clinical assessments more closely.

HTA—Easier to Reach Global Consensus Than an Agreement in Europe

While Europe and its citizens, like much of the rest of the world, continue to reel under the assault of COVID-19, the focus of many health authorities is understandably on vaccines, and the related research, development and–particularly as 2021 gets underway–production issues. But work is nonetheless continuing on planning for the health challenges that will still be there even when COVID-19 is under control. Late January saw Emer Cooke, the new executive director of the European Medicines Agency, fresh from a tough debate on vaccines in the European Parliament’s health committee, switch her attention to cancer, with an appearance at another of the parliament’s specialized committees.

Cooke was speaking at the parliament’s temporary committee on cancer, which has been set up specially in response to Europe’s Beating Cancer Plan–one of a number of health initiatives now emerging from the EU. Establishing her credential with the committee, she pointed out that EMA had approved 116 new cancer medicines over the 26 years of its existence, and in 2020 alone this included 11 products with new active substances–about a quarter of the 39 cancer medicines approved during the year.

The many challenges she identified in cancer medicine development are matched, she said, by “many solutions that we can see from our perspective.” And at the top of her list was improving clinical trials collaboration with downstream decision makers, as well as providing support to innovation. And she had some clear ideas on how this should be done, with a powerful emphasis on patient benefit as a priority.

In her view, “when talking about supporting innovation, we need to make sure that clinical trials are designed to answer the right questions.” For her, this means appropriately designed trials that not only promote innovation, but that also address the needs of cancer patients. “It’s only in this way that will be able to meet the evidence needs of regulatory authorities and downstream decision makers such as health technology assessment bodies, insurers, healthcare professionals and patients.” Cooperation is needed with those decision makers, and to ensure transparency of processes, and that requires better communication of information.

The focus must be on “trials fit for purpose from a patient perspective, and that ensure that patient views are systematically considered through the development process.” This is all the more true when research is confronting the particular challenges of rare and pediatric medicines, she underlined. But she saw this could be an opportunity, a chance for the EU to optimize the research effort by ensuring access to clinical trials and facilitating participation in them.

While remaining diplomatic, Cooke left no ambiguity in her estimation of the current degree of coordination at European level. “To do this we need to leverage the resources for conducting high quality research in Europe.” There is insufficient access to clinical trials—“and if we don’t facilitate access these trials just take too long to conduct.” At present, she pointed out, the majority of trials are conducted in only a handful of EU countries, and often only in a few centers. “There really are opportunities to bring trials closer to EU patients by promoting and enlarging the development of competences and trial readiness across Europe,” she said.

She also favors encouraging collaborative clinical trials by leveraging interaction between academia and scientists linked to regulatory bodies. This, she said, is necessary to address rapidly emerging regulatory science research questions, and to make a reality out of the concept of treatment optimization. “The EU needs to support clinical research into cancer treatment optimization with respect to all important clinical outcomes, real world effectiveness and safety. This will help to identify the population that is most likely to benefit. The continuation of data generation is necessary to inform the optimal use of medicines and the choices of patients and doctors,” she argued.

As she emphasized, clinical trials and drug development do not stop when a product is approved or reimbursed. “Evidence generation is a continuum which helps us to refine the understanding of what is the optimal use of new cancer medicines in clinical practice.” This she sees as a major opportunity for the EU to develop a learning healthcare system, which can maximize data generation in the real world by federating data from different sources–such as electronic health records and cancer registries. Regulators have a particular role in this, by identifying the open issues and helping to design the research questions that are needed.

But, she acknowledged, this needs the right infrastructure for systematically collecting, federating and sharing key data from different sources–and at present that is something lacking in Europe. That is why EMA is collaborating with the European Commission in the creation of the European health data space–another of the EU’s new initiatives.

It is also time to “refocus on designing quality into clinical trials.” For her, this includes applying risk proportionate approaches that systematically involve patients and a wide range of stakeholders in trial design. She said that EMA, along with other international regulators in the International Council of Harmonization, are making progress on this through updating of the fundamental good clinical practice guidelines for clinical trials.

Better communication could also decrease time lags and differences of view between approval decisions by regulators and access decisions by health technology assessment bodies. That in turn will benefit from progress on the EU’s now long-delayed HTA regulation, which should widen the scope for EMA to engage with HTA bodies. The right changes to pharmaceutical legislation–also up for EU review in 2022–and smarter regulatory practices can provide tools to help incentivize innovation. It should be possible to shorten review times, to make more use of priority schemes for innovative medicines, and targeted support through orphan designation.

“We are fully committed to delivering on the ambition of creating an enabling environment for the development, evaluation and access to new and re-purposed cancer medicines in the EU, and we stand ready to support the implementation of the European Beating Cancer Plan,” she concluded.

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

Cancer still a primary focus of EMA in light of COVID and vaccine development.

EMA’s Cooke Reviews European Cancer Prospects

One of the elements in the European Union's new plan for tackling cancer, launched at the start of February, takes the idea of patient care a step beyond treatment and into the issues that confront those who have survived cancer. Geared to take advantage of new technologies, research and innovation "as the starting point," this $4bn program will also embrace the entire disease pathway, from prevention to quality of life of cancer patients and survivors. So, in addition to promoting early detection through wider access to quality screening and launching a 'treatment for all' initiative for improved diagnosis and treatment, it will also devote attention—and funds—to rehabilitation, potential tumor recurrence, metastatic disease, and measures to support social integration and re-integration in the workplace. This extends beyond the natural domain of clinical trials professionals—but is part of a continuum that brings some additional light into those corners of patients' lives that can often remain somber even after the work of the clinical trials community has worked its own magic.

This novel attempt to bring some system into the post-treatment phase of cancer patients' lives is the result of a movement that has been gathering force in Europe over the last five years or so. It is a thoughtful response to the improved survival rates that advances in oncology have permitted—with an estimated 12 million survivors now in Europe. It is a conscious decision to shift the focus from ‘how long’ people live after diagnosis to ‘how well and how long’ they live.

Concrete plans include a ‘Cancer Survivor Smart-Card’ that will, from 2022, summarize clinical history and help in monitoring follow-up care, connecting the patient with health professionals to improve communication and coordination. A virtual ‘European Cancer Patient Digital Centre’ will help standardize the voluntary exchange of patients’ data and monitoring of survivors’ health conditions by 2023. The plan will also confront some of those practical obstacles that survivors often face, including in resuming their employment and in unfair treatment for patients in accessing financial services, even after long remission. So, re-skilling and upskilling programs will help cancer survivors re-join the labor market, and practices in the grant of loans or insurance cover will come under scrutiny. A specific chapter of this plan will look at the business practices of financial service providers "to ensure that only necessary and proportionate information is used when assessing the eligibility of applicants for financial products," with a particular emphasis on what is known as "the right to be forgotten."

The inclusion of these concerns in the EU's cancer plan—and in the parallel Cancer Mission the EU is also developing—is in part the result of a determined campaign driven over recent years by Doctor Françoise Meunier, a distinguished oncologist in her own right, and the widely-respected former head of the European Organization for Research and Treatment of Cancer. The challenges implicit in survivorship have preoccupied her since she retired from EORTC in 2015, and the plan has given formal status to these issues. Now, with those who are cured as the victims of unjustified discrimination, Meunier is concentrating on protecting them from being unfairly judged on the basis of a past which effective treatment has relegated to irrelevancy.

She told ACT that the way ahead is being shown by the adoption in four European countries of a legal framework outlawing such discrimination. "Today, the vast majority of cancer survivors across Europe are confronted with daily discrimination which sees them blocked from being able to secure the loans and mortgages they need to pursue their lives," she says. "Given the growing number of cancer survivors in Europe, we now have over 14 million reasons to discuss not only the need for an EU approach to the Right to be Forgotten but also the implementation of a right which has now been widely recognized by European policymakers." On February 19, she is organizing an event—

'14 Million Reasons to Discuss Life after Cancer'

—that will highlight progress and continuing challenges in implementing the right to be forgotten across Europe. It's a bit of a step away from the core interests of ACT readers—but it's an issue that affects a lot of people who ACT readers have helped to get where they are.

The $4 billion program will embrace the disease's entire pathway, from prevention to quality of life of patients and survivors.

Peter O'Donnell

Articles

Europe's Leaders Still Discussing How to Respond to the COVID Pandemic

HTA—Easier to Reach Global Consensus Than an Agreement in Europe

EMA’s Cooke Reviews European Cancer Prospects

Beating Cancer in Europe—And Beating Some of The Discrimination That Cancer Generates