The European Commission says it accepts that the implementation of the directive has been deeply flawed and will legislate to fix the problems by October 2011.
The Commission's health directorate – which was handed control of EU pharmaceutical policy earlier this year (EurActiv 30/11/09) – describes the Clinical Trials Directive as "arguably the most criticised piece of legislation" the EU has ever produced on medicines.
Officials are weighing up whether to simply clarify elements of the existing directive or to introduce a new regulation which would oblige national authorities to implement a streamlined version of the rules on medical research.
This would go some way to overcoming the inconsistencies that have arisen in how member states apply the directive.
However, there is some concern that MEPs could add additional levels of bureaucracy to any regulation proposed by the Commission – an argument in favour of examining other ways to tidy up research laws.
Directive adds costs and red tape
The scientific community's main criticism of the current rules is the increased costs and red tape that it has foisted on them.
The pharmaceutical industry is generally seen as having fared better, albeit at considerable cost. Nimble companies have adjusted to the new regulatory environment by adding staff and adapting their procedures.
But academics and doctors involved in research are not coping so well. This, according to Dr Ingrid Klingmann of the European Forum for Good Clinical Practice (EFGCP), is partly because academic researchers were not tuned in when the original directive was being drafted.
She says doctors with an interest in research failed to foresee the impact it would have on their work and now struggle with increased insurance costs and administrative responsibility.
"The clinical trials they were once able to do with a very low budget now face major cost factors. This means a lot of trials simply cannot be performed any more because it has become so expensive," Klingmann told EurActiv in an interview.
Efforts to ease burden 'backfires'
The European Commission has sponsored an FP7-funded project – the Impact on Clinical Research of European Legislation (ICREL) – to measure the effect of the directive on the pharmaceutical industry, academics, research ethics committees and medicines regulators.
"The outcome was very obvious: all stakeholders had to massively increase their staff to cope with the new requirements and the costs of clinical trials have gone up two-fold or three-fold," says Klingmann.
Some of the measures in the directive which were designed to cut red tape have backfired spectacularly. In an effort to reduce the number of reports which researchers have to make to the authorities, the Commission reinvented the criteria for reporting side-effects that arise during research studies.
The directive says that rather than reporting "serious adverse events" (SAEs), EU researchers would only have to report "suspected unexpected serious adverse reactions" (SUSARs). This effectively means authorities need not be notified of side-effects that are not directly relevant to medicine used in the trial.
However, with the rest of the world sticking with the more onerous SAE requirement, companies and academics conducting international trials were forced to comply with parallel reporting systems – thus doubling their workload.
Multinational trials within the EU have also suffered due to differences in how member states interpret the directive. Researchers seeking the green light from regulators and ethics committees in several member states have to work through different systems in each country before they begin their work.
This has been especially challenging for research on rare diseases which often requires multinational trials because the patient population in any given country is simply too small. For these kinds of studies, red tape tends to grow to unsustainable proportions.
"Originally, the hope was that there would be less reporting required under the current directive. In fact, we have much, much more," says Klingmann.
Ironing out these inconsistencies is one of the chief attractions of drafting a regulation on clinical trials – something the Commission's commits to looking at in its work programme.
No benefit for industry, researchers or patients
With rising economies in the BRIC countries – Brazil, Russia, India and China – rapidly developing their clinical trials infrastructure, attracting industry and researchers to Europe carries even more urgency than when the directive was first proposed back in 2001.
"Ultimately, what we can say is that if the aim was to make clinical research more attractive and to bring researchers into Europe, it has clearly not happened. In that respect, the directive has failed," says Kingmann, who note that some degree of harmonisation between authorities has developed since the new rules came into force.
India, in particular, has invested heavily in research and its pharmaceutical sector is rising rapidly and the government is actively working to attractive clinical trials.
Nonetheless, the impact has been felt differently across Europe. The UK, where the directive was enforced to the letter, has been hit hardest. In other countries, such as Italy, innovative ways of improving the research environment have paid dividends and the number of new studies has actually increased.
Companies conducting clinical trials in Italy must pay 5% of their marketing budgets into a public pot from which clinical trials are funded. Similarly, in France, a slice of authorisation fee paid by pharma companies goes to supporting clinical trials infrastructure in hospitals.
Meanwhile, patients have seen little benefit from the extra investment in staff and paperwork, according to Klingmann. Having access to innovative medicines at an early stage is something that benefits cancer patients, for example, so large teaching hospitals are often attractive because they are at the cutting edge of medical advances.
"We now have higher costs, more people involved and longer preparation time for applications without seeing any increase in the number of patients taking part in clinical trials. So we have made all that effort without having much impact on participation rates," she said.
Back to the drawing board
As consensus emerges on what the problems are, Brussels is now looking for common ground on potential solutions. The European Commission has published a "roadmap" outlining its commitment to addressing the shortcomings in the directive.
The Commission's most important task will be to decide whether to tweak the existing directive or draw up a regulation to harmonise research rules across the 27-member bloc.
Either way, the original 2001 proposal will be ten years old before new legislation is published to undo the damage.