New Year Challenges and Promises in Europe

The European Medicines Agency is at battle stations as the new year unfolds—and don't be surprised if you get a slightly grumpy response from them. It said at the end of 2012 that it expected about 100 applications for human medicines during 2013, including more than 50 applications for new medicines. This does not include designated orphan medicines, of which it is expecting about 20 new applications. Alongside, some 20 generic applications are expected. The figures are broadly similar to 2012, and the agency's predictions are in some respects a measure of optimism against a rather somber background.

Peter O'Donnell

At the most local level, the agency itself is strapped for cash and resources, while its responsibilities are increasing. It foresees "a difficult economic environment." It will be operating on a budget of €231.6 million ($307 million), slightly up from 2012, assuming fee revenue from services provided to companies reaches the planned level of €179.8 million ($238 million). At the same time, as a faithful servant of the European Union, it will have to put new legislation into effect.

The EU pharmacovigilance rules in force since mid-2012 are the most evident example. In 2013 the agency has to collect key information on medicines; prepare guidance for patient reporting; ensure better analysis and understanding of data and information; take regulatory action, particularly coordination of pharmacovigilance inspections; and widen its communications. But, as the agency points out, the fees that companies will have to pay for pharmacovigilance services are not expected before 2015. And on top of the pharmacovigilance rules, new EU legislation to prevent falsified medicines getting into the legal supply chain also comes into force in 2013. This will require the agency to become involved in developing an EU database of certificates of good manufacturing practice and good distribution practice from the 27 member states.

The strains are compounded by the obligation to conduct a constantly growing range of activities which generate no fee revenue (such as greater support to the scientific committees, monitoring conflicts of interests more sharply, or early-stage consultation and advice to applicants), and which have to be funded through cross-subsidisation from fee-generating activities. An internal program aimed at increasing efficiency of operations will continue, including bringing in a new information and communication technology strategy.

And above all, the agency is still going to be under close scrutiny from the European Parliament on many of the issues that plagued it in the preceding two years—not just the high-profile issues of avoiding conflicts of interest, but also financial and human resources management, and transparency. Guido Rasi, the Executive Director, has made big changes since he took over, but he now has to make a success of one of his flagship exercises in transparency—widening access to clinical trial data. Following a workshop on the subject in late 2012, the plan is to start a consultation process at the beginning of 2013, with a view to publishing a policy in early 2014 on the release of data from clinical trials.

Other clouds

There are other clouds on the agency's horizon. Not only the European Parliament has been examining the agency's operations. The Court of Auditors—the European Union's main watchdog—released a critical report on the agency's management practices in October 2012. The criticism was partly out of date because the report itself was nearly a year old when it was published, but the auditors are not going to let the agency out of their sights now that they have entered the fray.

Even more significantly, the European Commission has committed itself to a root-and-branch review of all its specialized agencies—there are more than 30 of them, dealing with subjects as diverse as trademarks and occupational health and safety, but the medicines agency is one of the most prominent. There is a growing feeling within the commission that these agencies are getting out of control—and control is one of the commission's principal roles within the European Union. So nothing can be excluded as the commission tries to bring new coherence to a plethora of these subsidiary operations set up more or less at random over the last 20 years: the result could be changes in their constitution, their mission, their scope of operations, their funding, or their supervision. The only thing it is almost certainly not going to result in is greater autonomy and independence.

So treat the agency gently if you want it to treat you gently over the coming months.

EU clinical trials rules

One subject that the agency's 2013 planning does not make any specific mention of is the ongoing attempt to update the EU's rules on clinical trials. In fact mild disappointment has on occasions been perceptible within the agency at the limited degree of engagement that it has been offered by the European Commission in this exercise: it was not formally consulted by the commission during the preparation of the draft regulation that appeared in July.

The discussion of this proposal is going ahead at several levels in Europe as 2012 ends and 2013 begins—and is being described by people close to it as "a very lively and hard debate." This column has already reported on some of the difficulties identified by ethics committees in the commission's proposal. Recent discussions have not eased their concerns, and many of them remain without any idea as to how they could handle the requirements, especially the tight new timelines envisioned, and the links that will have to be built by each member state between ethics committee assessment and regulatory review so as to obtain a single national decision.

The feeling is growing that a mention of "ethics committee" will have to be reinstated somewhere in the legal text (the term does not appear even once in the current draft of the regulation), both to match state-of-the-art regulation of clinical research, and also to provide reassurance that ethics committees will have a mandate to negotiate with their national health authorities about their role. For the timelines, on which ethics committee members are particularly concerned because they fear that tighter deadlines could jeopardize the quality of the existing review mechanisms, some leading European figures, such as Ingrid Klingmann of EFGCP, believe that compromise is possible, and some ways can be found to achieve shorter timelines without reducing the quality of reviews. She believes it will be necessary to give a lot of support to ethics committees in some countries, and that greater precision is needed in subjects like informed consent in vulnerable populations, definitions of concepts such as "low-intervention-trial," and arrangements for safety reporting or indemnity.

But many supporters of improved regulation—and there are many of them across Europe—are dismayed at what looks like almost total inaction by national authorities in trying to find ways of rising to the challenge posed by the draft regulation of developing a reliable and effective system for evaluating clinical trial authorization applications. Some observers put the member states' inactivity down to pique—because many suggestions from the national authorities in Europe were largely ignored by the commission as the draft was finalized. So far there is little evidence of national authorities coming together in any sort of formal (or even informal) task force to look at how they could fill in the blanks that the commission proposal leaves open for them.

Within the European Parliament, the discussion is still in a preparatory stage. The member who has chief responsibility for guiding the debates through the tortuous legislative procedure is a British socialist, Glenis Wilmot, who is leader of the European Parliamentary Labor Party and spokesperson for UK socialist MEPs on health. "I'm delighted to be steering this crucial piece of legislation through the European Parliament, and to be negotiating the final text with EU governments," she said in a statement when she was appointed to the task.

"There couldn't be a better time to be changing these rules. If we get them right they could create many skilled jobs in the United Kingdom and Europe, as well as leading to new life-saving treatments and drugs." She said she was aware that Europe's traditional dominance in medical research was at stake, and that the decline in clinical trials in the European Union in the last few years is "partly due to failures in the existing rules" as well as to competition from emerging markets.

"Simplifying the rules will encourage more European trials, not just by pharmaceutical companies but also by medical research charities and academic institutions," she said. Wilmott says the core issue for her will be trying to cut the administrative burden of carrying out a trial in several countries—"one of the most pressing problems with the current rules," she said. However, as this edition of Applied Clinical Trials went to press in late December, she had still not produced a draft report on the proposal, and formal discussions will therefore not start until January.

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