Danger: EMA Reputation at Risk

January 25, 2018
Peter O'Donnell

Applied Clinical Trials

As the EMA celebrates its 2017 highlights, the new year brings deeper challenges for the agency-including preserving the credibility of its patient-first mission.

The European Medicines Agency (EMA) started the new year with a pat on the back-from itself-for its performance in 2017.    It highlighted the 92 medicines the agency had recommended for approval, including 35 with a new active substance not previously authorized in the European Union (EU). Two of them were advanced therapy medicines, and 19 were orphan drugs, the EMA boasted.   As testimony to its agility, the agency pointed out that seven recommendations came after accelerated assessments, three were for conditional marketing authorizations, and two were for approval under exceptional circumstances. At the same time, it recommended 51 extensions of indication for existing medicines. And just in case anyone thought that these figures meant the EMA is a pushover, the agency added that it had issued six negative opinions, and 14 applications were withdrawn during the year.    Its 2017 “highlights” publication offers further demonstrations of this “good cop-bad cop” character. The EMA lists a dozen examples of the safety advice the agency had issued during the year, ranging from information about increased drug-related risks to recommendations to restrict usage or even suspend marketing authorization. And it notes that two centralized marketing authorization applications were withdrawn as a result of noncompliance with EU good manufacturing practice, and one as a result of good clinical practice (GCP) non-compliance. GCP inspections also resulted in rejections of applications and batch recalls of products already on the market. In addition, the agency gives high profile to the public hearing it held on valproate in September, as part of its ongoing review of safety in pregnancy.   All very laudable, no doubt. But 2018 already bristles with further challenges to the agency-and preparing for the transfer of its headquarters from London to Amsterdam is just one of them.    Image hit?   What is going to be even more of a challenge is safeguarding the reputation, the very credibility of the EMA, in a world which is changing faster than the agency is always able to respond to. For nearly two decades, the EMA has been the paragon of agencies, federating, coordinating, supporting, and pioneering in an ever-expanding Europe and an ever-more connected world. From its promotion for smaller firms to its key role in international harmonization, and from its management of the orphan drugs scheme to its leading thinking on adaptive pathways, EMA has been at the forefront of global and local drug regulation. But the context is changing, and the respect, even reverence, the agency has enjoyed, is changing too.   The signs can be seen in growing impatience among drug companies at the relatively slow pace of EU authorizations compared to the FDA. The disappointing performance of the scheme for advanced therapies authorization is another sore point with industry. Now Brexit is going to leave the EMA with severe transition problems and a gulf in regulatory skills once the UK splits away. And the cooperation that had been built up with the FDA is suddenly under question because the Trump presidency is transforming the policies and personalities of the administration in the US.   Even though few of these difficulties are directly attributable to the EMA-which is a creature of the EU and a victim of history-the net result is that the agency is no longer seen within the drug industry as quite the safe pair of hands and white hope for the future that it has represented until now.    If admiration for the EMA is diminished among those it might legitimately regard as its friends, the challenge is all the more acute in links with those who traditionally take a skeptical view of medicines and medicines regulators. January witnessed not just one but two set-piece debates in the European Parliament in Brussels where the merits of the agency were explicitly questioned.    Drugmakers' influence reaches too far into the agency's decisions, alleged a succession of civil society organizations and healthcare campaigners in a parliamentary debate in the first week of the new year. They demanded that the EMA accept more of the wider responsibilities that its prestige conferred on it, by accepting a role in discussions on limiting the proliferation of “me-too” products, on affordability of medicines, and on the merits of innovation. Veteran critic Silvio Garattini, the head of Milan's Mario Negri Institute, has been arguing since the 1980s in favor of a European requirement for relative efficacy criteria in drug approval, and claimed the EMA was still favoring industry by restricting its assessment to quality, safety, and efficacy without any obligation for evaluating comparative efficacy or any independent pivotal trial.   The agency should be "more proactive in ensuring trust and transparency" in its decision-making, by considering patients' interest above industry interests. It stood accused of being "dogmatic" in its response to queries about its judgments and about its "over-optimistic" views on research and real-world data. And the EMA should be doing more to police its links with the industry to eliminate conflicts of interest and to allay suspicions that its reliance on fees from industry had turned it into industry's lapdog.   Only a week later, the parliament's committee for overseeing spending took the EMA to task for being too close to the industry that it is supposed to regulate. A formidable list of more than 30 questions inquired into suspicions of "dependence on fees from the pharmaceutical industry," pro-industry bias in clinical trial data, "imbalance" resulting from industry's tendency to publish only positive trial results, patient-safety risks in adaptive pathways, and counterproductive secrecy over safety reporting.   Message reset    Most readers of this column will be more familiar than many critics with the EMA, and, hence, with the checks and balances the agency has put in place on its operations-and for those who are not, and wish to learn more, the EMA website has plenty of information. But it is not EMA's reputation among clinical trial professionals that is the only issue here. In a rapidly-changing world, the voices of those without specialist knowledge are coming to count just as much, if not more. And there is no shortage of compelling examples where vox populi has had a big impact. In EU policy terms, the fate of GM technology has been decided not on evidence, but on emotion. The ambitious anti-counterfeiting trade agreement the EU aimed to sign up to fell into an abyss in the face of public opposition. And in recent history, the election of Donald Trump and the result of the UK referendum on EU withdrawal have demonstrated-and are continuing to demonstrate-the power of rhetoric over reason.      That is why the agency will have to do more than assume that the views of men of goodwill are a guarantee of its future. The EMA’s website may be full of the most eloquent justifications of its actions. But that is not enough. A left-wing MEP deeply hostile to the EMA remarked-with almost grudging admiration-after hearing the arguments at one of the recent debates, "I'm not sure members of my committee know enough about the agency." The admission showed how even in what might be considered the seats of power for EMA, messages have not been getting through. If the agency is still battling to persuade members of the European Parliament that it is acting in the interests of society rather than of medicine manufacturers, it has not yet done its job in defending its territory. And that task is not going to be achieved by self-congratulation.      Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium  

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