Pharmacovigilance in the EU and under the Clinical Trials Directive

All is not well in the world of drug safety, it seems. Speakers and delegates expressed serious concerns about the European Union's new pharmacovigilance system. It is creating a huge bureaucratic burden for ethics committees and investigators, important differences exist between each country's interpretation and implementation of the regulations, and uncertainty surrounds the precise responsibilities of each partner in the clinical trial process.

A central aim of the EU clinical trials Directive is to bring a harmonized approach to reporting to improve patient safety, but judging by the comments of speakers at the seminar, much work still needs to be done.

Under the new system, investigators must report to the sponsor, and no longer to ethics committees (ECs). ECs only receive SUSARs (suspected unexpected serious adverse reactions) on a regular basis. Other safety information is sent to them only once a year.

An overall lack of clarity exists, said Dr. Mary O'Hare, a U.K.-based drug safety expert with AstraZeneca. It is unclear whether submission of annual safety reports (ASRs) should start in May 2004 or May 2005, whether ASRs should contain periodic or cumulative data, and whether the Common Technical Document applies to new products or to all products with ongoing studies in the EU.

AstraZeneca has sent SUSARs and quarterly line listings (QLLs) to hundreds of ECs and investigators. By the end of September 2005, it had sent 9 ASRs to competent authorities and ECs, but received no response or feedback. She fears some members states have not yet decided what they want industry to deliver. For instance, some authorities want all SUSARs, not just domestic ones, sent in a blinded manner to investigators and ECs. Also, there is an urgent need for ECs to become more experienced and better organized, she added.

Prof. Ernst Singer, chairman of Vienna Medical University's ethics committee, explained that ECs do not have the adequate expertise, support, and resources to cope with the new system.

"The directive is a valiant attempt to harmonize clinical research, but with regard to pharmacovigilance, it is tailored to a company environment, and to large Phase III studies in particular. It too often lacks clear definitions and guidance, allows too much room for interpretation, and thus self-obstructs its goals," he commented. More efforts are necessary to address the highly prevalent issue of under-reporting of adverse events, according to Dr. Michael Wolzt, a clinical pharmacologist at the University Hospital of Vienna. There are insufficient incentives for investigators to report adverse events, the reporting process creates a substantial extra administrative burden for already overworked staff, and many doctors are unaware of the importance, nomenclature, and procedural aspects, he said.

"We have to develop a policy to increase safety by improving monitoring, reporting, and prevention of adverse drug reactions. The support of industry is required to achieve preventable medication problems. The Thalidomide lessons need to be learned," he concluded.