I am very pleased to publish a guest blog by Annet Muestege, director and co-founder of Applied Clinical Services BV., which dives into the clinical aspects of the DRB report proposal in significant detail. Since I am only a lawyer, I am very happy with the clinical picture with respect to this proposal from someone as knowledgeable as Annet. Annet is also a blogger like me, and I recommend her blog Medical Devices Clinical. It does a great job of providing the clinical perspective in medical devices regulation. Are you a writer and interested in writing a guest blog like Annet and James did? Just let send me an email with a proposal.
So, take it away Annet:
ENHANCED PATIENT SAFETY?
Time and money, similar to pharma, that is what I think the changes to the proposed European Medical Device Directive will require when reading the Roth-Behrendt report. Looking at it from clinical research perspective:
Randomized Controlled Trials
The report seems to be driving towards a more medicinal product oriented approval process including randomized clinical trials. The phrase
“Clinical investigations for medical devices, where made compulsory in accordance with this Regulation, shall include randomized clinical investigations in the appropriate target population and well-controlled investigations”
to me suggests that a randomized clinical trial always is required as part of your pre-market clinical evaluation for the higher classes of medical devices. An activity that may be unnecessary or even inappropriate in certain situations – for example when an alternative treatment does not exist – and will demand a substantial larger clinical investment as compared to a single arm clinical trial.
Efficacy
The term efficacy is added throughout the report and at some points even seems to replace the term performance. The statement that
“Performance should notably be understood broadly so as to encompass efficacy and benefit to the patient, which shall be checked in cases where clinical investigations apply”
tells me the report is moving from the requirement to show clinical safety and performance before marketing authorization to clinical safety and efficacy. Proof of efficacy will require more and different clinical data and thereby will require a significant larger clinical investment in money and time.
Ethics Committee
The proposed amendment suggests adding a complete section regarding authorization of clinical investigations by independent Ethics Committees guarding the rights, safety and well-being of subjects participating in a clinical investigation. Nothing surprising there when you are used to following ISO 14155 for your clinical trials, but the explicit mentioning here does not leave room for any clinical investigations being conducted without Ethic Committee approval.
Postmarket surveillance
The report promotes a more pro-active attitude towards postmarket surveillance: requiring instead of suggesting the installment of registers for class IIb and III medical devices to collect experience related to the use of these devices. Together with the suggested independent scientific review of the PMCF evaluation report for class III medical devices, this will again add to the clinical administrative burden. When well handled though, this aspect of the report can also have a positive impact on patient safety for the higher class devices, and creates opportunities for the medical device industry for publications on long term product safety and effectiveness to drive market adoption as previously blogged.
Conclusion
Besides pushing towards a PMA like structure as Vollebregt and EUCOMED already mentioned, it seems the Roth-Behrendt report is moving towards a more medicinal product-like approval process. When implemented, the above elements will significantly add to the clinical evidence burden before market access and require a substantial investment in time and money, thereby delaying time-to-market. Also, I cannot help but wondering how these measures would contribute to enhance patient safety, which is the ultimate goal of the proposed changes to the European regulatory system. The only positive element in that respect I find is the enhanced attention to postmarket surveillance. To be continued…
medicaldeviceslegal 
Thanks for this. This gives me more insight on the proposal for clinical trials.
I am Regulatory affairs person managing Drug and Medical Devices products and we can see that Drug products are following a process for almost everything and this hasn’t avoided the issue with Mediator. On Medical Devices the Regulatory Affairs and Quality are really linked by the requirement of the Directive.
Usually we’re following the ISO 14155 for Clinical Trials, the 14971 for Risk Analysis, the ISO 13485 for Quality System, the ISO 10993 for Biocompatiblity tests and each time there is a concern we are trying to create a new standard to answer our questions.
Now with this PMA we will have to follow all this and then wait more than 200 days to obtain the approval of our product if Class III. Initially it was hard for Class III because the notified body was really reviewing every word of the dossier and sometime trying to find an issue where there is nothing because they are paid by us for that.
As I am not aware of everything, can you tell me if you had heard any issue on Medical Device product that were having a major issue on patient because there were not enough Clinical Trials or because the Clinical Trials were not made on the right way ?
Thanks for your efforts. Really appreciated.
Hi, I admit things are not getting better at all. I think you could find examples in the FDA document about insufficient (they say) EU clinical investigation of products, see my post https://medicaldeviceslegal.com/2012/04/27/eu-envi-parliamentary-committee-proposal-for-review-learn-the-lessons-of-this-fraud/