Will Europe's Regulatory Watchdog Come Of Age In 2014?

TheEuropeanMedicines Agency (EMA) is 20 years old this year — and it confronts many of the problems familiar to anyone at that age. After the vigorous growth and boundless optimism of its early adolescence, the agency now must make up its mind about what it wants to be. This is not just a matter of defining its personality. It also means taking on greater responsibility obtaining the resources it will need, and asserting its mission isuccessfully in the face of the often harsh realities of the outside world.

The agency's own sharpened awareness of the complex conditions beyond Canary Wharf is its programme for 2014, which identifies half a dozen new priorities. As EMA's executive director, Guido Rasi, publicly observed at the end of last year, "The environment in which we are operating is ever-changing, continuously presenting us with new challenges."

Clinical trials dust up

Perhaps the biggest challenge is the agency's intention to publish clinical trial data from marketing authorization applications. This has provoked criticism from industry that the EMA is going too far, while health cacpaigners contend it is not going far enough. Resolution may take longer than anticipated. Late last year the agency deferred its decision on precisely how it would disclose rtrial data as recently as December. As recently as December. Rasi was speaking of how "we will continue to discuss our approach to achieve this goal with our stakeholders so that we finalise a policy that is carried by a broad consensus." The cautious wording recognizes how contentious the debate has become — intensified by legal action that AbbVie and InterMune are taking against the agency's current, and much more limited, data-release policy, and by conflicting demands from the European Parliament that no clinical trial data should be regarded automatically as confidential.

Accelerating authorization

The other really tough issue the agency must confront is the longstanding disconnect between marketing authorization and drug reimbursement. For industry, the resulting delays in market access are seen as a disincentive for innovation, while the expanding demands of national health technology assessment agencies hold a threat of inefficient duplication. For patient groups, the concerns focus on inequalities of treatment and lack of access. And now even regulatory agencies are recognising the intrinsic risk of wasted effort and overlap that will please no one.

2014 will see EMA addressing "the evolving nature of our interaction with health technology assessment bodies." He sees the agency as moving towards running the processes of regulatory licensing and HTA assessments in parallel, "with the aim of accelerating and facilitating access to authorized medicines for patients".

His officials point out that the agency has been conducteding a growing number of parallel scientific advice procedures since 2010, and the aim is to build on that experience. The agency is planning for imminent release of draft guidance on how applicants can seek simultaneous feedback from regulators and HTA bodies on their product development plans. This work will also tie into the ongoing policy reflection exercise on the design of clinical trials that would allow for the development of more targeted medicines.

Regaining trust

One of EMA's big battles of 2014 will be to regain public trust in an era when the credibility of all authority has been called into question.

Hence major efforts will continue this year to boost agency transparency, and counter concerns over possible conflicts of interest. The work plan envisages publication of the agendas and minutes of EMA's committees, further increases in communication outreach, and yet more new rules about disclosure of interests to bolster the independence of dossier approved experts. The agenda of the agency's leading scientific body, the Committee on Human Medicinal Products, was published for the first time during the December 2013 meeting; minutes of the meeting will be published in January. It will then become standard practice to publish the agenda at the start of each meeting; and the minutes after their adoption the following month.

In December, the agency's management board endorsed a number of principles for revising the policy on conflicts of interests for scientific-committee members and experts. This latest rule-change aims at getting the balance right between maintaining a pool of high-quality scientific experts and ensuring that experts are free from undue financial or other interests. The principles, which are still to be turned into detailed rules, include concepts such as timing (how long before a past interest ceases to be a bar) and differentiation (experts involved in decision-making versus experts involved only in advice). There's the need, too, to recruit experts: to make involvement with EMA more attractive to scientists and physcians.

But many NGOs believe the rules are not being made sufficiently strict. Pierre Chirac of Prescrire and the Medicines in Europe Forum says EMA should strengthen its policy to protect decision-making from undue influence. He warns against what he calls the "unconscious link" between people who have worked together or have common interests.

Similarly, on the hot topic of access to clinical trial information, he insists that raw data should be made available to independent researchers. But he is not optimistic that EMA "will resist huge pressure from the industry". It has, he says, stopped providing Prescrire even with documents that contain no raw data.

By contrast, Richard Bergström, director general of the European industry association, EFPIA, is more optimistic about the data access debate. He believes that industry's concerns over protecting commercially confidential material are being taken into account as EMA finalizes its policy. He is more worried about how EMA plans to link drug authorization more closely to drug reimbursement.

Bergström is also concerned about ensuring that EMA opinions and decisions are led by top-quality science, and over the best allocation of regulatory resources in the face of tighter healthcare budgets and ever-greater workloads. The issue is complex, he suggests, since it cannot be solved merely by concentrating available talent centrally: national authorities will also have to remain adequate and credible if they are to ensure national buy-in to decisions taken at the centre.

Weighty pharmacovigilance

As if all this were not enough, the agency is determined to boost international cooperation, particularly on inspection of clinical trial sites outside the EU, and to contribute to the combat to the search for new anti-infective treatments.

The implementation of the pharmacovigilance legislation that came into effect in July 2012 will continue to impose new workloads in 2014, as will implementation of the falsified medicines legislation. At the same time, the agency is also introducing modifications to its fee structure, and undergoing a major internal reorganisation this year, with redesigned processes and rearranged departments. And its work will be further disrupted by a physical move, relocating its 1000 staff members to new premises just down the road in London docklands, along with 500 items of loose furniture, 3000 personal crates, 5000 linear meters of filing, and 260 plants.

If the agency plays its cards well, it could dispel the memories of those unfortunate blemishes that marred its adolescence, and look forward to resuming its evolution as a world-leading centre of regulatory excellence. If it doesn't, the agency could find itself, rather like the European Union of which it is a part, losing its way in a world changing faster than it can keep up with.

Reflector is Pharmaceutical Executive's correspondent in Brussels.