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Patient safety, orphan medicines featured in EU's six-year research support budget.
It could be a happy new year for clinical trials in Europe. The European Union agreed—just in time—on its research support program for 2007–2013. The agreement, reached only in December and which came into effect on 1 January 2007, allocates more than €54 billion ($64 billion) to European research over the program's seven-year life.1
It isn't all scheduled for clinical trials, however. The money is to be shared among a wide range of European research priorities. But the program does make substantial provision for life sciences. There will be more than €6 billion specifically for health, with further allocations for biotechnology, nanosciences, and nanotechnologies.
It will also provide support for initiatives such as European networks of advanced clinical research centers; bio-banks and genomic resources; high security laboratories for emerging diseases and threats to public health; and model testing facilities for biomedical research.
The European Parliament, which had a hand in the preparation of the program and has many members with sharp sensitivities over ethical considerations, did oblige the EU member states to accept some limits on medical research. But the compromise reached imposes conditions that are less severe than had been feared by many researchers earlier in the year. And Parliament also insisted on boosting the focus on research into children's health, respiratory diseases (particularly those induced by allergies), and neglected diseases.
EUÃÂ´s Compromise on Research Ethics
Among the last-minute modifications to the provisions on health research, the Parliament insisted on support for:
"Translating the results of clinical research into clinical practice including better use of medicines (e.g., with a view to avoiding the development of antibiotic resistance), and appropriate use of behavioural, organisational and public health system interventions and health therapies and technologies. Special attention will be given to patient safety, including the side-effects of medicines; to identify the best clinical practice; to understand decision making in clinical settings in primary and specialised care; and to foster applications of evidence-based medicine and patient empowerment with a view to enhancing patients' personal and social autonomy. Focus will be on the benchmarking of strategies; investigating outcomes of different interventions including medicines and new health technologies, taking into consideration pharmacovigilance evidence, specificities of the patient (e.g., genetic susceptibility, age, gender and adherence) and cost benefits in terms of health, quality of life and good practice."
Some of the program's broader aims will also offer potential backing for different aspects of clinical trials and drug development. These include support for cooperation between universities, industry, research centers, and public authorities, and training and career development of researchers. The program will also set up an autonomous European Research Council to support investigator-driven "frontier research," and it will promote coordination and development of research infrastructure, regional research clusters, and smaller firms.
This isn't the EU's first multi-annual research support program. There have been six since 1984, and they have each helped produce some results in clinical trials. But they have in the past been heavily criticized by researchers for their procedural complexity. Many laboratories and firms have stopped applying for grants under the programs because they found the gains didn't justify the pains.
This new version of the program aims to avoid the same trap.
The new year brings another change to the European Union: it has grown to 27 member states—with Bulgaria and Romania taking their place alongside the 10 other new members that joined in 2004. This may make the European medicines market bigger, but it brings new complications with it too. And in preparation for this new expansion, the European Medicines Agency felt it appropriate to issue new enlargement-related guidance for sponsors of orphan medicines.
The EU's legislation on orphan medicines, with its procedure for designating medicines as orphans and its incentives for their development and launch, has been in force since 2000. But the rules apply only if the sponsor is "established" in the EU. From 1 January 2007, the EMEA has made it clear that individuals or companies from the two new member states will be considered as meeting that eligibility requirement.
That's fairly straightforward. But because one of the qualifying criteria for orphan status is limited European prevalence of a condition, the calculations of prevalence have to be adapted to the new situation, too.
Bulgaria and Romania between them bring some 30 million new citizens into the EU—almost a 10% increase. The calculation inevitably changes for the number of persons affected by the condition in the EU at the time the application for designation is submitted. The new rule is that for applications submitted from 1 January 2007 onward, prevalence calculations must be based on the population of the enlarged European Union—and that means 27 member states (as well as Iceland, Liechtenstein, and Norway, which are not EU members but who years ago chose to throw in their lot with the EU on these questions).
The same enlarged EU will be the reference base for another of the eligibility criteria for orphan status—the nonavailability of methods for diagnosing, preventing or treating the condition targeted by an application. It is the responsibility of the sponsor to establish that no satisfactory method of diagnosis, prevention or treatment of the condition has been authorized in the EU (or that, if a method exists, the medicinal product will be of significant benefit to those affected by the condition). So from the start of 2007, sponsors will be required to include and review existing methods in the new 30-country market.
For translations, life also becomes a little bit more complicated, since Bulgarian and Romanian have become official EU languages with the accession of these two countries. At the time an application for designation is made, the agency requests translations into all the official languages of the European Union for not just the international nonproprietary name of the substance but also the proposed orphan indication.
That means the information must appear in all the following languages: English, Bulgarian, Czech, Danish, Dutch, Estonian, Finnish, French, German, Greek, Hungarian, Italian, Latvian, Lithuanian, Maltese, Polish, Portuguese, Slovak, Slovenian, Spanish, Swedish, Romanian, Norwegian, and Icelandic.
And there's no easy escape for applications submitted before the latest enlargement became a fact. Decisions on orphan designations granted after the start of 2007 will have to be translated into all the official languages, including those of the new member states, plus Icelandic and Norwegian.
The only relief is that decisions on orphan designations granted prior to January 2007 have been automatically extended to Bulgaria and Romania on the day they became member states. Similarly, EU marketing authorizations for orphans automatically extend to the new member states from their date of accession. And the EU-wide market exclusivity granted to an orphan extends automatically to Bulgaria and Romania.
The European Union faces a huge problem in adapting its own operating mechanisms in its enlarged form. And so far, it has come up with very few sustainable ideas about how to do this. The attempt to win agreement on a new constitutional treaty for the enlarged EU was severely wounded by public rejections in referendums in France and The Netherlands in 2005.
Germany, which took over the rotating presidency of the EU at the beginning of 2007, has promised to do what it can to find consensus on new operating rules—but warns no one should expect miracles. The complexities in conducting trials in Europe are therefore likely to persist until resolution is found on broader and deeper political questions in Europe.
Watch this space. You will be the first to be told when the skies start to clear. Meanwhile, Happy New Year!
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.
1. European Union Seventh Research Framework Programme; details on: http://cordis.europa.eu/fp7/.