Nancy J. Stark is president of Clinical Device Group, a medical device clinical consultancy based in Chicago. Recently she has noticed an increase in requests for clinical evaluations and offers advice about how to write clinical evaluation reports to meet the requirements of notified bodies.
“Where you begin depends on where you are now,” says Stark. “Either you are writing a clinical evaluation for a new, pre-approval device or for a medical 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.”
How do you proceed with clinical evaluations if you are still designing the device?
Stark: If you’re still in the stage of designing your medical device, start by identifying its intended uses. Then evaluate the existing clinical data to determine if it is sufficient to support safety and performance per the Essential Requirements of the Medical Devices Directive or the Active Implantable Medical Devices Directive, or if you need additional clinical data. If additional 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.
What if you have a commercial medical device that is already on the market?
In this case the notified body has informed you that the clinical evaluation is overdue or needs updating. They may give you a grace period, but you are expected to get busy. Follow the same process of evaluating the existing data to determine if it is sufficient to support safety and performance for the intended uses. If the clinical evaluation report concludes the existing data are insufficient you are in a difficult situation—you’ll need to suspend sales until additional data are acquired.
What is the best approach for writing a clinical evaluation report?
You need a team of at least three individuals: a medical writer, an information specialist, and a statistician.
You will also 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 and is operated by the U.S. National Library of Medicine. It 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.
A typical clinical evaluation involves the following steps and durations:
- Identify key questions—1 week
- 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 and complaint file—2 weeks
- Write final evaluation—1 week
The first step of a clinical evaluation report is evaluating the existing literature data—what is the best way to do this?
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. A good approach is the following:
- 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 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. 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.
What’s next in meeting the requirements for medical device clinical evaluations?
Review any existing clinical investigations 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.
How do you handle any complaints that might be on file?
You must examine the complaint file against the risk management system. The notified body will 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 clinical evaluation report as an annex.
The medical writer then takes the literature review, sponsored study review, and risk management review altogether and reaches an overall conclusion of whether the existing data support the medical device’s safety and performance for the intended use, or if additional clinical data are needed newly. If new clinical data are needed, you know what happens.
If the data are sufficient, then 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.
Nancy J. Stark is president of Clinical Device Group (www.clinicaldevice.com). Contact her at 773-489-5706 or firstname.lastname@example.org
Pilgrim Software representatives will be at the 2012 RAPS Regulatory Conference October 26-30 in Seattle. Please stop by and visit us at Booth #216 to discuss your specific company challenges in a global regulatory environment.