Originally Published MDDI November 2004

EDITOR'S PAGE

No place in the world has more-stringent requirements for medical device clinical trials than the United States. It is a mistake, however, for firms to consider European clinical trials a comparative walk in the park.

EU nations are now expecting trial sponsors to follow ISO 14155, “Clinical Investigation of Medical Devices for Human Subjects.” It has more requirements and a higher level of standardization than the document it replaced, EN 540, “Clinical Investigation of Medical Devices for Humans.” In particular, there is more guidance on document and data control, patient tracking, and informed-consent procedures. Also, there is more clarity in the division of responsibilities between the investigators and the sponsors of European clinical trials.

“There is now more of an emphasis on quality assurance and quality control for clinical investigations,” Danielle Giroud, president of d-Target (Yverdon, Switzerland), told attendees at September's MEDTEC conference held in Galway, Ireland.

The information that must be contained in a clinical investigation plan (CIP) includes:

• The objective of the study and the supporting rationale.
• The design of the clinical investigation. What is the product being compared to, and why?
• The statistical considerations expected to be taken into account.
• The methods for reporting any adverse events experienced in the trial.
• The conditions for early termination of the investigation.

Another new development is that careful accounting of all patients who withdraw from a clinical study is now demanded. “You must document them very clearly,” Giroud said. “Otherwise, authorities might ask if you are trying to hide something.”

Of course, some EU nations have their own requirements that go beyond those in the harmonized documents. It is essential that firms learn what these requirements are, Giroud said.

She noted that the ISO document outlines all the elements of what should be on the informed-consent forms, “but in terms of confidentiality needs, you should go farther than what ISO says. In most cases, you just have to explain what information is being collected and where it will go. But some countries, including Sweden, France, Norway, and Denmark, have additional procedures. The EU's Data Protection Directive says that what you do in one country is OK for all the others. That is not always true.”

Indeed, a goal for future revisions is to match the International Council on Harmonization's good clinical practice documents. However, those contain a lot of pharmaceutical terminology, so don't expect a convergence anytime soon. Diligent research into device-specific requirements of individual European nations will remain a necessity for some time.

Format counts for almost as much as content. It's important to the competent authorities that the information be presented clearly, said another MEDTEC speaker, Barbara Tucker, who is the medical assessor for medical devices at the Irish Medicines Board. She also emphasized that the product design should be frozen once the CIP has been submitted to the competent authority. “There is no time for the competent authority to revisit amendments,” she said.

There will be more refinements to the document before it becomes the catchall envisioned by its authors. For example, Giroud said, more specifics about auditing are needed, as is a consensus on how ethics committees should be constituted.

However, the incompleteness of some aspects should be no excuse for device companies to underestimate the document's importance. Europe is often the first frontier for testing a new medical device. Failing to follow proper procedure for a European clinical trial can set back a product's entire development timetable. There is now even less margin for error.

The Editors

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