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Experts Question Impact of EU Directive on Research

Lewis Rowett

The European Union (EU) Directive on Good Clinical Practice is set to be implemented in May 2003 and fully applied by May 2004. But there is some concern in the cancer community that the directive may actually hold back important clinical research.

The goal of the directive is to establish a single, harmonized legal framework for drug trials in EU member states. But Francoise Meunier, M.D., Ph.D., director general of the European Organization for Research and Treatment of Cancer (EORTC), warned that, for the directive to succeed, its implementation into national laws must take pan-European research into account as well as independent academic clinical trials not focused on drug approval. The directive will apply the same rules—in terms of good manufacturing practice, good clinical practice, and labeling—to trials of new regimens of already approved drugs and to clinical trials of investigational drugs, adding an additional administrative burden to the system.



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Dr. Francoise Meunier

 
"It would be extremely detrimental if the implementation of the directive within national legislation is not taking into account the network of investigators conducting ... trials with registered drugs," Meunier said in November. "At a time when the European Commission and the European Parliament wish to boost cancer research, to maintain existing expertise in Europe, and to promote our international visibility, any serious drawbacks and threats to the competitiveness of European research should be avoided at all costs."

The directive was first proposed to the European Parliament in 1997, and the final version was approved in April 2001.

Meunier expressed concern that there were too many key topics in the directive that are open to too broad an interpretation by national authorities. Issues covered in the directive include ethical approval and protocol amendment procedures, regulations for serious adverse event reporting and informed consent documentation, requirements for drug labeling, costs of non-sponsored trials, translational research issues such as exchange of tumor materials and tissue research, and insurance requirements by ethics committees.

The directive establishes a legal basis for ethics committees and outlines standards for the manufacture, import, and labeling of investigational medical products while providing for quality assurance of clinical trials. Compliance with these standards will require the EU member states to set up inspection systems for good manufacturing practices as well as for good clinical practices. The directive does not, however, distinguish between commercial and noncommercial clinical trials.

"Nonpharmaceutical research plays a vital role," said Meunier. "It is often best positioned to detect medically relevant differences in diagnostic and therapeutic interventions that could translate into major public health advances. There is a real risk that European public health policy-makers and national authorities may marginalize key areas of biomedical and health research by developing policies without fully taking into account the scientific environment and economic structure of independent research."

Criticism of the directive has come from researchers in many fields, including cardiology, neurology, and emergency medicine. Meunier, however, believes that cancer research is especially vulnerable. "Its complexity calls for multidisciplinary teams of scientists and clinicians to offer [multiple treatment modalities]. There is clearly an increasing need for the academic community to conduct more strategy trials not only involving new drugs but also combinations of registered drugs with surgery, irradiation, etc."

For Genevieve Decoster, head of good clinical practice training for Hoffman-La Roche in Basel and co-chair of the European Forum on Good Clinical Practice’s Clinical Trials Process Working Party, it is not clear that these problems will be unique to cancer research. "I worked for more than 20 years in academic cancer research before joining the pharmaceutical industry and I understand Francoise’s concerns. Very many cancer patients in Europe are treated within research protocols and oncologists will have to change their approach, but there is no reason to see cancer research as a special case. Or rather, there is no specific medical area that cannot be a special case."

She emphasized the implementation guidance documents for the directive are still in draft form. The guidance documents cover specific topics such as documentation to be submitted to ethics committees, registration of clinical trials with the European clinical trials database (EUDRACT database), inspection procedures, and suspected unexpected serious adverse reaction (SUSAR) reporting. "The directive is finalized and must now be enacted," she said, "but the guidelines are not finished, and I think they will be changed considerably before they are approved. The regulatory environment in Europe has changed because of drug safety issues and patient protection issues, and these changes are not to be resisted. At this stage I definitely would not panic."

The potential value of these implementation guidance documents is also stressed by the European Agency for the Evaluation of Medicinal Products (EMEA). Speaking for the EMEA, Martin Harvey said, "In drafting the directive, existing national legislation was taken into account. ... In pan-European legislation of this kind there is always the potential for interpretation problems. In this case, however, the directive allows specifically for the provision of interpretive guidelines. The guidelines are an opportunity for sectorial concerns like these to be addressed."

The extant draft guidelines were issued by the European Commission in July 2002, and this was followed by a formal 3-month consultation exercise. Although there had been some criticism that the draft guidelines had not been published alongside the directive, many people expected revised versions to be issued by the commission before the end of 2002, but these did not appear.

Meunier, however, remains unconvinced. "I have not changed my views since [November], and I am not encouraged by the guidance documentation so far produced," she said. "The EU Directive on Good Clinical Practice does not improve the quality of science and cancer care, nor does it protect patients’ safety. This directive was aiming at promoting high-quality Pan-European clinical trials and the end result may be the opposite."



             
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