Clinical Evaluation Reports Now Required for All Medical Devices in Europe

There are changes sweeping European medical device regulations and these changes affect every company that markets devices in Europe. A 2007 amendment to the Medical Device Directive MDD 93/42/EEC will come into force in 2010. The bottom line of the amendment is that every medical device sold in Europe, regardless of its classification, must have a Clinical Evaluation Report in its technical file.

History & Background
How did such a sweeping change come about? In June 2002, the "Report on the Functioning of the Medical Device Directive (NBM/061/02)," concluded that most manufacturers didn't possess adequate clinical evidence for their medical devices and that most Notified Bodies didn't adequately verify the clinical evidence that was provided to them by manufacturers. The findings applied to Class I and Class IIa devices, as well as Class IIb and Class III devices.

In addition, the European Commission's Medical Device Experts Group (MDEG)--composed of representatives from EUCOMED, EDMA, CEN, CENELEC, NB-MED, EAAR, and each member-state's competent authority--cited clinical evaluations as a major area of concern. A sub-group of MDEG, the Clinical Evaluation Task Force (CETF) proposed the changes found in Directive 2007/47/EC which led to the amendments of MDD 93/42/EEC.

MDD 93/42/EEC as Amended by Directive 2007/47/EC
"Clinical data, even for Class I devices, will generally be required," states the preamble to the 2007 Directive (see Recital 8). Clinical data are the safety and performance information generated from the use of a device. Clinical data are sourced from: 1) new clinical investigations, 2) literature reviews of published clinical investigations, and 3) unpublished reports from the manufactureres biological safety files, bench testing files, complaint files, or other internal information.

Annex I of the amended MDD now states that "Demonstration of conformity with the Essential Requirements must include a clinical evaluation [i.e., the assessment and analysis of clinical data] in accordance with Annex X." Hence the conclusion, that every medical device sold in Europe must be supported with a Clinical Evaluation Report in its technical file.

Notified Bodies Call for Updated Clinical Evaluation Reports
One consequence of the new regulations is that European Notified Bodies are marching their way through medical devices and asking manufacturers to update their Clinical Evaluation Reports. Even devices that are already commercialized are being required to have updated Reports.

Clinical Evaluation Reports - A Three-Legged Stool
Think of a Clinical Evaluation Report as a three-legged stool. One leg is a report of any newly conducted clinical investigations on your device. Another leg is a report on your unpublished data, such as biological safety data, bench testing data, or complaint and experience records. The final leg is a literature review of clinical investigations published on other, similar devices.

Furthermore, for established devices, the literature review may serve as the primary source of clinical evidence to support commercialization and may justify not conducting clinical investigations newly.

Databases
A note to Americans, it isn't enough to search MedLine. While our free, online database from the National Library of Medicine includes over 19 million citations back to 1948, there are about 2000 global medical journals that aren't included here. EMBASE, owned by Elsevier Publishing, gives access to MedLine citations and to the other 2000 journals, using full-featured Boolean logic under the product name of EMBASE.com. Ovid and Dialog are simply alternate services with different front-ends to access the same data. To do a Europe-friendly literature search, you'll need to have access to EMBASE.

How to Do a Literature Review
Thorough Clinical Evaluation Reports :
[1] Identify the purpose of the review.
[2] Identify the sources from which you'll take your articles: e.g., Medline, Google, abstracts or full articles, reviewed scientific literature or unreviewed or unpublished data, etc.
[3] Decide on any filters or limitations, e.g., no articles before 1985, only articles on a well-defined topic, only articles that relate to your indication for use, etc.
[4] Gather the articles and list them in a table.
[5] Read the articles, some may be excluded--perhaps there are two articles about the same study, state the reason for exclusion in the table.
[6] Read the remaining articles again and exclude the articles that are redundant or irrelevant or unusable for other reasons, state the reason for exclusion in the table.
[7] Weight each article according to relevant criteria.
[8] Analyze the data with regard to the number of patients, success or failure of device, adverse events, etc.
[9] Draw conclusions based on original purpose of the review.
[10] Prepare a report. [Buy a CD webcast on this topic.]

Report Format
The report will have a predictable format.
[1] Purpose of the review.
[2] Description of the device.
[3] Intended use, indications for use, and claims. [Example]
[4] Selection criteria for literature articles.
[5] Summary and grading of clinical data.
[6] Data analysis and evaluation.
[7] Conclusions.

We Can Help
Clinical Evaluation Reports are even more important in Europe today than they ever were. If conducting a well-designed report seems daunting and time-consuming, especially with Notified Bodies demanding updates on commercial devices, let CDG help you. With trained professionals on both sides of both ponds (we have experts in Japan, EU, and the States), we have the capability to address all three legs of the Clinical Evaluation Report on your behalf. Email us with your request at cdginc@clinicaldevice.com.