MDR Clinical Evaluation Plan

[Reg1000]

Hello,

MDR Annex XIV requires a clinical evaluation plan. One of the aspects it says should be included is:

— an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;

Any ideas on what to write to cover this?

Thanks!

 

[EmiliaBedelia]

This depends 100% on what type of device you have. To rephrase it, this is asking you to define "What are the key criteria that you will use to define whether your device is performing well or not?" In the same way that you need a protocol before executing verification testing, you need acceptance criteria before you do a clinical evaluation.

You need to figure out what the "benchmark" is for acceptable performance for the type of device. For example, in orthopaedic implants the revision rate is a common performance benchmark. If you have an amazing device with a revision rate of 30%, but all your competitors with similar devices have a revision rate of 5%, that would raise questions of whether your device is "state of the art".
The calculus of whether a risk is acceptable or not also depends on the indications/intended use of the device. In orthopaedics, a pediatric patient with bone cancer is basically guaranteed to need a revision surgery later in life. The alternative treatment is amputation. The benefit to the patient is that they keep their leg. A higher revision rate is acceptable because the benefit to the patient outweighs the risk.
For a 70 year old with osteoarthritis, however, revision surgery is an additional risk to the patient. The benefit to the patient is increased quality of life. There are other non invasive therapies that can help. Therefore the benchmark revision rate is lower.

Your clinical evaluation should align with your risk documentation and your intended use/indications for use, so I would start there to identify risks, benefits, and the different use cases for your device. You should also consider what data is generally available, as it would do you no good to identify a benchmark you can't collect.

 

[Reg1000]

This is very helpful, thank you.

My devices have no direct clinical benefits, their clinical benefits will be in part related to either the performance of other devices that they are used with or how the information they generate is acted upon.

I would therefore also welcome any other examples available for devices where the benefits may not be quite so straightforward.

 

[EmiliaBedelia]

It is hard to say without knowing exactly what the devices are, but there has to be SOME level of performance that you expect from the device in order to provide some benefit to the user/patient. Some of the definitions from MDR might help to clarify what you need here.

- Article 61 (1) of MDR states "The manufacturer shall specify and justify the level of CLINICAL EVIDENCE necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of CLINICAL EVIDENCE shall be appropriate in view of the characteristics of the device and its intended purpose."

- Article 2 (52) MDR defines clinical performance as the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a CLINICAL BENEFIT for patients, when used as intended by the manufacturer

- Article 2 (53) MDR defines CLINICAL BENEFIT as the positive impact of a device on the health of an individual, expressed in the terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health

You as a manufacturer are responsible to ensure that the devices are performing as intended by conducting post market surveillance/post-market clinical followup. If your device does not have a clear benefit on its own, you may be able to justify that PMS data is sufficient clinical evidence to demonstrate that the device is meeting its intended purpose and thereby enabling a clinical benefit to be received by the patient.

Again, this is all really dependent on the specifics of your device. I think you need to be very clear on what exactly your device is intended to do. If your device is providing information or inputs to another device, you need to consider accuracy and risks associated with that interaction. Even if you don't see a clear "benefit", there could be a "harm" experienced if your device does not fulfill its purpose - which is part of what the clinical evaluation and risk/benefit analysis is intended to cover.

 

[Ronen E]

Very good advice up there from @EmiliaBedelia (finally, someone to help here!... haha).

2 more comments:

1. Welcome to the muddy swamp that is "Benefit-Risk <something>", where vagueness abounds, existing MDR definitions are only semi-helpful, and we (as well as NBs) shape things up as we go. I know it doesn't sound too professional but that's the truth (at least as I see it).

2. The exchange above demonstrates well the limitations of this forum (and others like it). To provide full, accurate and useful answers, we'd typically require information - and quite a lot of it - that can't (or can't practically) be shared on a public forum.

 

[Noha Ahmed]

This depends 100% on what type of device you have. To rephrase it, this is asking you to define "What are the key criteria that you will use to define whether your device is performing well or not?" In the same way that you need a protocol before executing verification testing, you need acceptance criteria before you do a clinical evaluation.

You need to figure out what the "benchmark" is for acceptable performance for the type of device. For example, in orthopaedic implants the revision rate is a common performance benchmark. If you have an amazing device with a revision rate of 30%, but all your competitors with similar devices have a revision rate of 5%, that would raise questions of whether your device is "state of the art".
The calculus of whether a risk is acceptable or not also depends on the indications/intended use of the device. In orthopaedics, a pediatric patient with bone cancer is basically guaranteed to need a revision surgery later in life. The alternative treatment is amputation. The benefit to the patient is that they keep their leg. A higher revision rate is acceptable because the benefit to the patient outweighs the risk.
For a 70 year old with osteoarthritis, however, revision surgery is an additional risk to the patient. The benefit to the patient is increased quality of life. There are other non invasive therapies that can help. Therefore the benchmark revision rate is lower.

Your clinical evaluation should align with your risk documentation and your intended use/indications for use, so I would start there to identify risks, benefits, and the different use cases for your device. You should also consider what data is generally available, as it would do you no good to identify a benchmark you can't collect.

could you please provide some tips on risk benefit ratio assesment , our devices is orthopeadic implants and i found your comment is very useful , so how should i conduct benefit risk ratio , what are the main steps ?

 

[EmiliaBedelia]

FWIW, my experience is entirely limited to regulatory - I am not a clinical expert, and I don't know anything about your specific product, so take this as a non specific general opinion from a stranger on the internet...

The process for orthopaedic implants is the same as for any other device.
You need to start with understanding all the risks of using the device and the therapies/treatments involved. This is not just limited to the device itself and potential failure modes, it would also include the therapeutic risks. Surgery in general has a lot of risks involved. No matter how perfect your device is, it cannot mitigate the risk of being under anesthesia, for example (unless you have an extremely innovative completely noninvasive implant... ). You also need to proactively gather information about device use in the field, including both your own post market surveillance data and competitive products/"state of the art" to ensure you are capturing all of the potential patient harms that may occur. This needs to be aligned with your PMS/risk management as well - anything you identify as part of the literature review should feed back into those processes.
Finally, you need to understand the actual benefits to the patient that they experience from using your device.

IMO, all this requires a very detailed understanding of your device and its actual clinical usage. This is why you need a clinician involved who is familiar with the therapy. There are many guidance documents and even a template available from MDCG... I would definitely recommend a read of these as a starting point. If you are totally lost, this is an aspect that you should really consider getting a dedicated consultant for. Especially for a Class III device, your notified body is going to be ALL over the clinical aspect, and it's something that they have been hammering hard in reviews.

 

[Lissa]

an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;
Could you please give an example for surgical glove. is there any source i can read to set the benchmark.

 

[VI Me]

an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;
Could you please give an example for surgical glove. is there any source i can read to set the benchmark.

Based on the intended purpose, materials and intended clinical benefits that you have defined for your surgical gloves, you would need to plan and conduct a review of the published literature and any applicable standards/guidelines relating to surgical gloves.

This is your State of the Art review.

Using the literature/standards you can then define what are the key/important performance characteristics of a surgical glove, which of these are applicable to your glove, and how are these typically measured.

Are there any generally accepted standards specifically relating to the manufacture of surgical gloves for example that might define the quality standards and specifications that manufacturers need to meet?

You would the use the information to feed into your CEP to outline your critical performance parameters, and plan how you might measure and validate those performance criteria based on the state of the art, using what is reported in the literature/standards as the benchmark that you would need to meet.

You can also use the sources you identify to determine any known risks/safety concerns and what safety outcomes might be measurable that feature in the literature concerning surgical gloves, and use this to help guide your risk criteria, establish 'acceptable' risk thresholds and plan your risk mitigation strategy for your risk file.

By defining your clinical performance benchmarks and safety thresholds, with reference to the state of the art literature/standards you have met the requirement.

For a glove I believe a lot of the critical performance of a glove would be based on how its material performance, durability, permeability, wear characteristics, barrier properties etc. are important for its intended clinical purpose, any risks related to material sensitivity etc. and additional considerations for whether there are any added coatings for antimicrobial purposes etc.

 

[Avril Chen]

Perhaps someone would like to share how an analysis of the clinical benefits and clinical outcome parameters of a diagnostic device such as a urodynamic system should be better phrased? Much appreciated!