What Do Notified Bodies Want?
A Clinical Device Whitepaper by Nancy J Stark
We've seen an uptick in requests for clinical evaluations recently, and I thought it would be worthwhile to review the requirements. Where you begin depends on where you are now: 1) writing a clinical evaluation for a new, pre-approval device, or 2) writing a clinical evaluation for a device that is already commercial. In the first case, you are asking the question, "Do I need new clinical data for certification?" In the second case, you are bringing your documentation up-to-date.
Clinical evaluation reports for pre-certification devices
If you're still in the stage of designing your device, you begin by identifying its intended uses. Then you evaluate the existing clinical data to determine if it is sufficient to support safety and performance per the Essential Requirements of the MDD [1 MDD] or AIMD [2 AIMD], or if you need additional clinical data. If additional clinical data are needed you have the choice of revising the intended use or performing a clinical investigation.
Once you believe the data are sufficient, you convince top management to grant a CE Mark and sign the Declaration of Conformity to your previously certified quality management system. Finally, you will discover the truth when the Notified Body comes to make an inspection call.
Clinical evaluation reports for commercial devices
The more common situation is that your device is already on the market in Europe, and the Notified Body has informed you that its clinical evaluation is overdue or needs updating. They may give you a grace period, but you are expected to get busy. You follow the same process of evaluating the existing data to determine if it is sufficient to support safety and performance for the intended uses. Should the report conclude that the existing data are insufficient you are in a difficult situation: you'll need to suspend sales until additional data are acquired.
Because the consequences of determining the data are not sufficient are so financially significant for your firm, and the consequences of determining the data are satisfactory are so financially favorable, it is wise if the report writers are as far removed from the device designers as possible.
To write the report you need a team of at least three individuals: 1) a medical writer, 2) an information specialist, and 3) a statistician.
In addition you need a written procedure for how to proceed, a report template (useful, but not required), and access to literature databases such as Medline. Medline is easy to use, it is operated by the US National Library of Medicine and is available to anyone with a browser. Medline provides access to 5400 worldwide journals in 39 languages dating from 1947 to the present. And it is free.
Date Wheels for Clinical Evaluation Planning
A typical clinical evaluation involves the following steps and durations:
 Identify key questions—1 weeks.
 Identify databases to search—overlaps.
 Identify search scope, keywords, search strings—1 week.
 Review abstracts, discard with reasons—1 week.
 Acquire articles—2 weeks.
 Read articles—1 week.
 Weight articles for relevance, discard with reasons—overlaps.
 Weight articles for statistical validity—1 week.
 Medical writer summarizes literature—2 weeks.
 Review sponsored clinical trials, if any—0-2 weeks.
 Review risk management system & complaint file—2 weeks.
 Write final evaluation—1 week.
Date Wheels are a handy, pocket-sized calendar used by project managers to quickly plan simple schedules. If the clinical evaluation work begins on March 1, you can hope for a final report about three or so months later, or about June 1. Buy them here.
A Three-Legged Stool
The first leg of a Clinical Evaluation Report is an evaluation of the existing literature data. The Global Harmonization Task Force (GHTF) Study Group 5 document "Clinical Evaluation" coupled with MEDDEV 2.7.1 Rev 3, which is slightly easier to read, are the guidances that tell us how to do the literature evaluation.
Here's what the medical writer—working together with you—will do:
 Define the key questions.
 Identify the databases to search (Medline, Embase, MAUDE, Cochrane).
 Define scope of search and search strategies using a qualified information specialist.
 Scan the abstracts to identify articles for review.
 Acquire full-texts of articles.
 Weight the articles for technical significance, discard anything with a low weight.
 Have a statistician weight the articles for statistical significance, discard anything with a low weight.
 Review only those articles with the highest weightings; see averages below. The literature data are evaluated to determine if they support safety and performance of the device for its intended use. I like to prepare a separate literature review and attach it to the main clinical evaluation as an annex. The literature review annex has several required elements including the search strings used by the information specialist, a list of abstracts scanned, the articles reviewed, their weights and justification for those weights, and full-text copies of the articles.
The second leg of the evaluation is a review any existing clinical investigations that your firm may have sponsored. These data are reviewed separately from the literature because you have closer access to the details. The writer asks questions such as: "Was the Declaration of Helsinki followed?" or "Were adverse events resolved?" If not, those facts are noted in the report but the data are not used.
Once the writer is satisfied that ethical and administrative requirements were correct, he/she reviews the study results to see if they support safety and performance of the device for its intended use. I like to prepare a separate sponsored study review and attach it to the main evaluation as an annex.
In the third leg, the medical writer comes to the most sensitive step of all; examining the complaint file against the risk management system. They review the file to see if complaint handling, as dictated by the risk management system, supports the safety and performance of the device for its intended use. I like to prepare a separate risk management review and attach it to the main evaluation as an annex.
The Clinical Evaluation
Finally, the medical writer takes the literature review, sponsored study review, and risk management review altogether and reaches an overall conclusion of whether the existing data support the device's safety and performance for the intended use, or if additional clinical data are needed newly. You know what happens if new clinical data are needed.
The Technical File
If the data are sufficient, the clinical evaluation is filed away in the Technical File, a written procedure describing the writer's strategy is incorporated into your quality management system, and you wait with baited breath until the Notified Body inspector comes.
How long, how much
There are only two questions in top management's mind: 1) how long will it take, and 2) how much will it cost. The answers are simple: "It depends." Let's say you have a very nice ultrasonic toothbrush and you intend to use it for cleaning roadside burns—the kind of burn you get when your motorcycle crashes and your skin scrapes against the pavement. The toothbrush is used to remove the dirt, grit, and tarmac from the wound. It's an unusual intended use and raises all kinds of questions about potential damage from the bristles, safety features to prevent over-brushing, effects of ultrasound on open wounds, comparing gum tissue to wound tissue, instructions for use, and so on. A clinical evaluation for cleaning wounds will take longer and cost more than a report for brushing teeth with the same device.
CDG can help
Clinical Device Group is poised and ready to help you with writing your evaluations. We have medical writers, information specialists, experienced statisticians, a written procedure, a standard template, and a proven process. Clinical evaluations written by our specialists have been reviewed by at least three different Notified Bodies and all have been accepted. We work collaboratively with a point-person on your side so that you are involved in the process every step of the way.
 Medical Device Directive 93/42/EEC.
 Active Implantable Medical Device Directive 90/385/EEC.
 Global Harmonization Task Force, Study Group 5, Clinical Evaluations. https://www.ghtf.org/sg5/sg5-final.html
 MEDDEV 2.7.1 rev 3. https://ec.europa.eu/enterprise/sectors/medical-devices/files/meddev/2_7_1rev_3_en.pdf
Nancy J Stark, PhD
President, Clinical Device Group Inc