BioWorld Today Correspondent

LONDON - Anger about problems created by the European Union's 2001 clinical trials directive boiled over at an expert meeting Wednesday, with Professor Rory Collins of Oxford University's clinical trials unit alleging that "The EU is committing a serious mistake that is killing and disabling many people." He accused the European authorities of "fiddling while Rome burns" by failing to reform the legislation.

To loud applause from many of the 250 participants at the meeting, he claimed that the directive's check-box approach was generating an obsession with formal compliance with rules, but was distorting the search for genuinely useful information from trials - particularly in advanced therapies.

"The preoccupation with good clinical practice is fundamentally flawed," he asserted, arguing that the new rules have doubled the costs of running non-commercial cancer trials in the UK, led to delays of up to 12 months in trial initiation and prejudiced larger trials.

Collins urged redrafting of the rules so that they would promote more trials, larger and randomized, rather than tie researchers down with masses of often pointless paperwork.

He sharply dismissed suggestions that allowing researchers more flexibility would lead to higher levels of fraud. Most misconduct targeted by the EU rules are "unlikely to affect study results," he said. Instead, he maintained, the rare instances of fraud in clinical trials are generally so inconsequential that the public is at greater risk from studies that are poorly designed, wrongly analyzed and inappropriately reported.

Many other criticisms of the legislation were expressed by industry executives and academia at the meeting. Speaking for the European Biopharmaceutical Enterprises, Mats Ericson of Wyeth also spoke of its "fundamental flaws." Allowing each of the 30 countries covered by the directive to conduct their own assessment of a request for clinical trial approval was "a waste of resources," and led to "a motley of divergent national decisions," he said.

Alan Morrison, vice president of international regulatory and safety at Amgen, said that despite earlier hopes that the directive would make Europe more attractive for clinical trials, "the potential benefits have not yet been realized. There is an urgent need to address fundamental issues."

He highlighted the extra work and uncertainty created by loose definitions, notably over reporting requirements for adverse reactions, by slow and often contradictory processes for obtaining regulatory and ethics committee approval for trials and by divergent requirements for investigational products.

Speaking on behalf of the European biotech industry association, EuropaBio, he complained that the already heavy administrative burden of the EU rule was increased by the frequent imposition by individual member states of additional - and "unreasonable" - requirements. Efficient development of biopharmaceuticals demands greater harmonization, transparency and consistency in approach across the EU, he urged.

Currently, the provisions are open to misinterpretation and misapplication of the law by member states, said Aisling Burnand, chief executive of the UK's BioIndustry Association, in a statement released during the meeting. "Differences in the implementation of the directive by member states have adversely impacted on the ability of companies to carry out multinational trials across Europe. The impact on small and medium sized companies is particularly significant because they do not have sufficient financial and manpower resources to deal with the additional administrative burden and consequent delays."

"There is a need to find a way forward," admitted Thomas Lönngren, executive director of the European Medicines Agency, which hosted the meeting. He underlined the need for Europe to remain competitive in the international clinical trials market: "We want to keep high quality clinical research and drug development in the EU," he said, pointing to figures showing that of the quarter of a million patients worldwide taking part in trials in the two years to September 2006, a third were in Europe.

Europe's research spending is buoyant, too, with annual investment comfortably exceeding €2.5 billion (US$3.6 billion) for the last three years.

Alarmingly, on both counts, Europe significantly lags the U.S., warned Lönngren. The ability of pharmaceutical firms to choose the location for their operations is not playing in Europe's favor either, he added. In 2001-2006, 17 research sites in Europe were closed, and only two were opened, while the U.S. saw six openings and only five closures, and Asia saw 14 new ones and just one closed down.

Georgette Lalis, a senior EU official with specific responsibility for pharmaceuticals, acknowledged the problems, including the failure by many member states to follow the guidance the EU issued on how to assess and monitor trials. But she said there would be no instant solutions or major reforms, and offered only some prospect of better coordination among national authorities. The governments of the EU member states - who are the ultimate decision-makers on all EU rules - have no enthusiasm for changing legislation that has only recently been introduced, she said.

That view was endorsed by leading figures from national regulatory agencies in Germany, the Netherlands and the UK. Kent Woods, chief executive of the UK's regulatory authority, said the best that could be hoped for in the foreseeable future was "incremental improvements."