European Medicines Agency Under Attack

If you missed International Clinical Trials Day this year, you are certainly not alone. It took place, apparently, on May 20, and is celebrated every year on or around that date, in commemoration of the day that James Lind started his trial comparing treatments for scurvy, back in 1747.

With some small embarrassment, given that I have been writing about clinical trials for more than 15 years, I am obliged to admit that I had never heard of International Clinical Trials Day until this year. And I would probably still be ignorant of it were it not for a press release from the European Medicines Agency in London.

Peter O’Donnell

The agency "supports International Clinical Trials Day," it announces. And it goes on to explain that the aim of the day is to "enhance communication and coordination of clinical trials between countries, resulting in better clinical research that is relevant to the needs of patients everywhere." That is certainly a noble goal. But I can think of an even better one—and one that the EMA may also share right now.

EMA troubles

In early May, the EMA suffered a new reverse in its fortunes, when the European Parliament voted against clearing the agency's accounts, because of concerns over its management. This decisive thumbs-down from the European Union's watchdog on spending was just the latest setback in an annus horribilis (an annus and a half, really) for the beleaguered agency.

As reported in this column (and in many other channels), trouble started for the hitherto spotless institution when its former Executive Director, Thomas Lonngren, jumped ship to work for the drug industry at the beginning of last year.

Management board complicity in the move generated additional anxieties over how secure the agency was against conflicts of interest. Only weeks after that imbroglio, the Mediator circus came to town, when suggestions were made that the agency had somehow been negligent in pushing for re-assessment of the antidiabetic from Servier.

A delay of almost a year before filling the vacant post of executive director didn't help improve the agency's image in the outside world. And by the time the new boss started work late last year, the agency was facing another major challenge—threats by the European Parliament's health committee to refuse to accept the agency's accounts pending adequate assurances that management was fully in charge and doing its job, particularly over averting conflicts of interest among experts, staff, and management.

Until recently, the agency had been hopeful of averting humiliation. It had supplied numerous details of new methods put in place to meet MEPs' concerns. But in the end, the health committee remained adamant that not enough evidence had been provided of a new broom making a clean sweep. And it persuaded a majority of the Parliament to refuse approval of the accounts.

The new boss (no longer really new) is left casting about for ideas as to how to prove his agency is now whiter than white.

Damaged reputation

In the meantime, the damage done to the agency's reputation is huge, and persists. From being a world-renowned paragon of virtue in international regulatory circles, it has fallen to the level of a suspect. Public perception too has been negatively affected by the repeated attention to its alleged deficiencies. So it is little surprise that the agency has seized on the opportunity of International Clinical Trials Day to offer a reminder of what its core purpose really is—and to point out how it is fulfilling those responsibilities.

In what looks like a clear rebuttal of the Parliament's suggestions that the agency is no good because of some oversights in largely administrative matters, the press release states clearly that "the majority of the agency's scientific work is centred on the review, coordination, and supervision of clinical trials."

It then sets out at some length to explain how it goes about discharging these tasks in easy-to-grasp layman's terms. It describes its scientific evaluation work as involving "the review of clinical trial data that are included in the application information from a pharmaceutical company when seeking marketing authorization." It underlines its role in providing scientific advice on the design of clinical trials conducted as part of medicine development, and decisions on clinical trial design in pediatric investigations. And it notes its provision of scientific guidance on the design and conduct of clinical trials in specific therapeutic areas.

The agency also flags up its "central role" in ensuring application of good clinical practice at the European Union level, and its activities as host of the EU clinical trials register on behalf of EU Member States and as developer and coordinator of the EudraCT database used by national medicine regulatory authorities to enter clinical trial data from clinical trial sponsors. Its recent guidance on how clinical trials outside the European Union should be conducted also gets a mention.

In other words, the agency is basically doing a good job, it would have us believe. It highlights the very concrete and positive benefits of its activities, implicitly relegating to a secondary level of importance the areas where it still stands accused of inadequacy. It is an understandable and indeed even a sensible way to proceed. While it is not for this column to presume to pass judgement on any of these weighty matters, it is plain to anyone with eyes to see that a certain disproportion risks creeping into discussions of the EMA—and, indeed, of other institutions, some of them closely linked to the European Union.

Unwanted spotlight

Accusations naturally attract attention—and not just in the media. The accusations against the EMA have attracted wide attention. They have also colored perception of the agency, because in nearly two decades of existence the agency has remained almost anonymous, unknown to the world outside medicines regulation. Its first public appearance is in the defendants' box, and the first public discussion of its activities has taken place against a febrile background of claims of gross misconduct.

In consequence, the risk exists that the general perception of the agency is deeply negative—irrespective of the validity or relevance of the accusations it faces.

That is bad news for the agency. But it is also bad news for the clinical trials community. Because if the agency's credibility suffers, so too does the credibility of everyone subject to its regulation. And no one in the world of medicines development needs any reminders of the perils of lost credibility—whether it be among patients, physicians, regulators, or investors.

So it is a smart move by the agency to try to redress the balance by invoking the merits of clinical trials in general, and the merits of its own involvement in ensuring high standards in their conduct.

And just for the record, this is a brief list of the changes that the agency has introduced over recent months in a bid to demonstrate that it is managing its affairs well.

The agency has a policy on the handling of conflicts of interests for its scientific experts, including committee members, which was last updated and endorsed in March 2012. It says it takes a proactive approach to identifying potential conflicts of interest and searching for alternative experts where necessary, and to help achieve this, all experts must complete a declaration of interests form every year.

The agency screens each expert's declaration of interests to decide whether or not to include him or her as a member of a committee, working party or other group. It assigns each expert a risk level based on whether the expert has any interests, and whether these are direct or indirect. To assure transparency, completed declarations of interests and risk levels for all experts are available in the European expert list on the agency's website. After assigning a risk level, it uses the information provided to determine if an expert's involvement should be restricted or excluded in specific activities, such as the evaluation of a particular medicine. It bases these decisions on the nature of the interests declared, the time since the interest occurred, and the type of activity that the expert will be undertaking. Experts can only be involved if they have signed a declaration of interests form and the agency has assessed those interests. All proposed members for its scientific committees have their declarations of interests screened before their formal nomination.

In March 2012, the agency endorsed a breach-of-trust procedure setting out how it deals with incorrect or incomplete declarations of interests by experts and committee members. Similar rules have been introduced governing agency staff and members of the agency's management board.

The coming weeks will determine how far and how fast the agency can clear its name fully, and how soon it—and the wider clinical trials community—can get on with some real work, free from suspicion.

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