In Europe the second quarter of 2016 is characterized by several big steps from clinical perspective: In April the General Data Protection Regulation (GDPR) entered into force, in June consensus was reached on the new Medical Device Regulation (MDR), and also in June, the MEDDEV 2.7/1 revision 4 was published. Although the latter concerns a medical device guideline and is not legally binding, I am sure it will impact the clinical evidence needs for medical devices in Europe. In this post I wanted to share a couple of aspects that struck my attention on the new version of the MEDDEV:
Reading the new version of the MEDDEV, I cannot get away from the impression it anticipates the new MDR: For example the conformity assessment with requirement on performance (Appendix A7.3) describes 1:1 the MDR definition of clinical performance:
“the ability of a device to achieve its intended purpose as claimed by the manufacturer, including any direct or indirect medical effects on humans as well as the clinical benefit on patients resulting from the technical or functional, including diagnostic characteristics of a device, when used as intended by the manufacturer”.
Similarly the instructions to update the clinical evaluation throughout the product life cycle with clinical data along with its frequency (see below), is as described in the MDR. So to me it seems the new MEDDEV more or less enforces compliance with a regulation yet to be.
Clinical Evaluation scope
The requirements on content of the clinical evaluation report concerning claims on safety, performance, and risk/ benefit weighing seem comparable to the previous version, but the scope of the clinical evaluation has broadened. The clinical evaluation, for example, should start during the product development phase, and in addition to the clinical data should include review of all information materials. Where information material
“refers to the labelling, instructions for use and the manufacturer’s promotional materials for the device under evaluation”,
so goes beyond the IFU and product labelling, and includes marketing materials.
Product Life Cycle
The clinical evaluation is also much more an ongoing process throughout the full product life cycle, beginning at the start of the product development and continuing after CE mark. The revision 4 includes an indication as to when the clinical evaluation report should be actively updated: at least annually in case of high risk devices, and every 2-5 years in case the device does not carry significant risk.
Post Market Clinical Follow Up (PMCF)
Post Market Surveillance (PMS) has become much more a fixed part of the clinical evaluation. For CE-marking the purpose as specified in revision 4 is two-fold:
“document that there is sufficient clinical evidence to demonstrate conformity”,
“identify aspects that need to be addressed systematically during post-market surveillance”,
and one of the tasks of the clinical evaluator is to determine the needs for PMCF. Besides any residual risks, (s)he should also take into account any uncertainties or unanswered questions, such as for example on long-term performance and wide-spread use, to assess the needs for PMCF studies. Especially in case of implantable devices, I am pretty sure this will lead to more post-market studies as it will be challenging to address all of that in pre-market studies, a topic I will address in my next post on clinical evidence dilemmas.
Clinical Investigation requirements
The revised MEDDEV is rather explicit as to when clinical investigations are needed and what clinical data should look like to support safety:
“For compliance with Annex X section 1.1.a MDD and Annex 7 AIMDD, clinical investigations with the device under evaluation are required for implantable and class III devices unless it can be duly justified to rely on existing clinical data alone.”,
“the clinical data should contain an adequate number of observations (e.g. from clinical investigations or PMS) to guarantee the scientific validity of the conclusions relating to undesirable side-effects and the performance of the device”.
With respect to safety the new MEDDEV even includes a table with sample size thresholds as to what would be considered an adequate sample size depending on the estimated probability of observing an undesirable event. In other words, the new MEDDEV 2.7.1 will demand more and larger clinical studies to substantiate safety and performance.
In anticipation of the new MDR, the tasks of the clinical evaluator have been extended, and the demands with respect to clinical evidence tightened under the new MEDDEV 2.7/1. With more attention to detail including the total product package, the full product life cycle, and higher demands for pre- and post-market clinical studies.
Obviously there is more to be said about the revised MEDDEV than addressed in this blog: For example what to think about the qualifications of the evaluator, and the requirements for a device to be assumed equivalent? Feel free to contact me in case you want to discuss, you will find my contact information in the upper right corner of my blog.