The Medical Device sector concerns a wide variety of products and the proposed European Medical Device Regulation attempts to regulate the pre- and postmarket clinical evidence base under one umbrella. Driven by scandals such as with the hip and PIP implants the regulatory bar on clinical evidence requirements will be raised, and with the EU Parliament adopted amendments to Medical Devices Regulation proposal being out and the EU Council debate on it in December, it is interesting to see what we are heading for.
Previously, I blogged regarding the Postmarket Surveillance and Postmarket Clinical Follow-up, and an updated presentation you can download here. A presentation summarizing the main elements with respect to the Premarket Clinical Evaluation you can download here, and reviewing the consolidated text for the MDR from AXON lawyers on the clinical evidence needs for the Clinical Evaluation, one can identify the following five drivers:
Next to safety and performance, the definition of Clinical Evaluation includes the term clinical benefit:
“‘clinical evaluation’ means the assessment and analysis of clinical data pertaining to a device in order to verify the safety and, performance and clinical benefits of the device when used as intended by the manufacturer.”
and it defines benefit as:
“the positive health impact of a medical device based on clinical and non-clinical data”
So, regardless the class of the device, the clinical evaluation should include evidence showing a positive health impact of the concerning device in addition to demonstrating safety and performance. This becomes kind of interesting for some of the lower class of devices, and one may wonder who will pay the bill in the end.
Medical Device Classification
The scope of the Medical Device Directive has been extended and more devices will be classified as Class IIb or III. Class IIb and III devices will require clinical evidence collected via a clinical trial, notably a Randomised Controlled Trial (RCT):
“In the case of devices falling within Article 43a(1), with the exception of those used for a short term, clinical investigations shall be performed”
“As randomised controlled investigations usually generate a higher level of evidence for clinical efficacy and safety, the use of any other design or study has to be justified.”
Basically the current version of the of the MDR says a RCT is needed for Class IIb and Class III devices, and one will have a hard time arguing when not considering it necessary to go through such costly and time consuming effort.
Existing Clinical Evidence
Similar to the current medical device directive, existing clinical evidence can be used for the clinical evaluation, provided product equivalence can be proven. The proposed MDR, however, is much more outspoken on what equivalence means:
“Equivalence can only be demonstrated when the device that is subject to clinical evaluation and the device to which the existing clinical data relates have the same intended purpose and when the technical and biological characteristics of the devices and the medical procedures applied are similar to such an extent that there would be not a clinically significant difference in the safety and performance of the devices.”
and the need to check independent sources:
“Data from independent scientific institutions or medical societies based on their own collections of clinical data shall also be taken into account.”
To me this is indicative for a much stricter policy with respect to the use of existing clinical evidence than is the case under the current MDD.
Medical Device Claims
When no existing clinical evidence is there to demonstrate safety and performance, a clinical trial is needed, and here the term efficacy is introduced:
“Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the technical performance of the device, the clinical safety and efficacy of the device when used for the intended purpose in the target population and in accordance with the instructions of use, and the manufacturer’s claims for the device …”
As previously blogged, demonstrating efficacy will require more and different clinical data than performance, and thereby will require a significant larger investment in time and money.
Another interesting element with respect to clinical investigations is that the proposed MDR specifically references the control therapy and the involvement of independent experts in relation to the RCT:
“Also the choice of the control intervention shall be justified. Both justifications shall be provided by independent experts with the necessary qualifications and expertise.”
Indeed, defining the control arm is one of the most critical, but also challenging elements when designing a RCT: Standard of Care and therefore the control arm therapy unfortunately is not identical and changing in different countries and for different health care experts. When designing your Premarket RCT it is therefore key to define your primary market first.
Under the proposed MDR clinical evidence requirements for the Premarket Clinical Evaluation will be more stringent than before, and there will be more attention for clinical benefit and efficacy as compared to the current MDD. I sincerely hope that this effort is outweighed by an improved patient safety & health benefit as intended.
Although the EU MDR is not finalised, and it is hard to predict when that is going to happen with the EU Parliament elections coming up, we get a pretty good picture as to what it is we are heading for. I will keep you posted.