EU directive ‘puts people’s lives at risk’

Europe is suffocating vital new medicines under a mass of paperwork - putting at risk both patient welfare and the industry’s prosperity. That was the alarm sounded last week by hundreds of leading researchers from across Europe.

Meeting at the EU’s Medicines Agency in London, they demanded radical changes to harmonise the rules on medicines testing.

"The EU is committing a serious mistake that is killing and disabling many people," said Professor Rory Collins of Oxford University’s clinical trials unit. Mats Ericson, a molecular biologist at Wyeth Research in France, spoke out against "fundamental flaws" and "waste of resources". Aisling Burnand of the UK’s BioIndustry Association said innovation was being blocked as smaller hi-tech firms become overwhelmed by the administrative costs and delays in the current system. For Stefan Bielack, a paediatric oncologist from the Olgahospital in Stuttgart, the current rules meant massive waste-paper production and "time spent on nonsense".

This uncharacteristic language from a community more comfortable in laboratories than lobbying has been provoked by a well-meaning piece of EU legislation that has gone badly wrong. The culprit, according to researchers, is the directive on clinical trials, which was intended to align the controls that each member state imposes when a medecine is tested on patients - that lengthy and decisive phase in the development of every new medicine.

In 2001, when EU member states adopted the directive, they flatly rejected the European Commission’s initial proposal for an EU-level system of authorisation and control of clinical trials. Sensitivity over medicines testing - which inevitably involves ethical as well as scientific judgements - resulted in imprecise legislation that virtually allowed each member state to retain its own system.

The price of this national sovereignty was persistent complexity. Researchers are still required to obtain separate approvals from regulatory authorities and ethics committees in every member state where any part of their trial takes place. Since modern medicines are increasingly developed in multi-centre cross-border trials, the consequence is more red tape, costs and delays - producing what Ericson called "a motley of divergent national decisions".

Collins claimed that the new rules had doubled the costs of running non-commercial cancer trials in the UK, caused delays of up to 12 months in trial initiation and prejudiced larger trials. Major research-based drug firms, too, say they face serious problems. Alan Morrison, vice-president at Amgen, highlighted the uncertainty created by loose definitions, national inconsistencies in reporting on trials, obtaining approval to start a trial and importing or labelling products under test. "Efficient development of biopharmaceuticals demands greater harmonisation, transparency and consistency in approach across the EU", he said.

But EU regulators do not want to change the legislation. Instead, they have tried, over the last five years to iron out flagrant national differences through dozens of guidelines and talk of some form of mutual recognition. Hartmut Krafft, Germany’s representative on a special clinical trials working group set up by the member states, insisted that many of the problems could be solved in the current legal framework, simply by ensuring greater coordination among member state authorities. Brian Davis, the UK representative on the group, acknowledged gaps in the current system, but was dismissive of the need for major legislative changes. Kent Woods, the UK agency’s chief executive, said the best that could be hoped for in the foreseeable future was "incremental improvements".

Researchers remain unsatisfied by this approach. They say that guidelines have merely made matters worse, cumulatively enshrining each member state’s individual concerns in an ever-growing body of EU requirements. Bielack said that the result was an obligation on researchers to supply "too much garbage to too many recipients". Worse, according to Morrison, the member states do not even comply with the guidelines themselves, "unreasonably continuing to expand the rules with their own additional requirements".

Even the senior Commission official attending last week’s meeting, Georgette Lalis, the director responsible for pharmaceuticals in DG Enterprise, accepted that criticism. "Guidelines do not lead to harmonisation," she said. "Some member states comply with them, but the great majority do not." But conscious of member states’ reluctance to revisit the legislation, she could promise no more than an extensive consultation exercise and a gradual search for solutions.

But trying to muddle through threatens both academic research and the international competitiveness of the European pharmaceutical industry, researchers maintain.

For Silvio Garattini, director of the Istituto Mario Negri in Italy, faced with red tape that quadruples the cost of trials, approval of international studies has become so complicated that, he said, independent trials were disappearing.

Christine-Lise Julou, of the European Federation of Pharmaceutical Industries and Associations, told European Voice that she was sceptical that mutual recognition and guidelines could provide the needed breakthrough. She said that she could only hope that the EU authorities would act now when they see that there is a real problem - "for the sake of the European research industry’s future".

• What do researchers want?

A procedure for a single European approval per study on the basis of a single scientific assessment, with a European body to arbitrate between conflicting national views, and clarification of the many imprecisions in the legislation.

• What are the chances of getting it?

An EU-level procedure was rejected in 2001 - and it is likely to be even more difficult to get the necessary legislative change through the Council of Ministers in an EU of 27 member states, according to Eamonn Corcoran of the Irish Medicines Board.

• What’s at stake?

Thomas Lönngren, a director of the European Medicines Agency, stressed the need to "keep high quality clinical research and drug development in the EU", which currently conducts about a third of all trials worldwide with research spending of more than €2.5 billion a year. But Lönngren warned that Europe is lagging behind the US, and research is moving away to other parts of the world. In 2001-06, 17 research sites in Europe were closed and only two were opened, while the US saw six openings and only five closures, and Asia saw 14 new ones and just one closed down. "Europe’s share of global expenditure on clinical trials is shrinking. This trend appears to be steady and there are few, if any, signs that the trend is bottoming out, let alone reversing itself," said Francis Crawley, executive director of the Good Clinical Practice Alliance-Europe.

• Peter O’Donnell is a freelance journalist based in Brussels.

Europe is suffocating vital new medicines under a mass of paperwork - putting at risk both patient welfare and the industry’s prosperity. That was the alarm sounded last week by hundreds of leading researchers from across Europe.

• Primary Source