There are a couple of guidances and a couple of documents that help in determining what clinical endpoints are, what counts as a valid endpoint and what type of endpoints can be considered.
Section c gives detailed information on how clinical benefits can be identified. It gives information on how these endpoints for these clinical benefits can be identified. What factors you should consider.
For example, it is essential to consider the duration of the clinical benefit experience by the patient. Is your device resulting in a short term benefit, is your device resulting in a benefit that extends over years? If there is an improvement in the quality of life, how long is that expected to last? These are some of the things that you are expected to identify and call out within your clinical evaluation plan, and then demonstrate via suitable data in your clinical evaluation report.
So oftentimes it’s that identifying these endpoints becomes a little bit of an issue. We’re not very sure what kind of endpoints we should consider for each benefit. Here is the guidance and consensus documents around the clinical condition of interest that your device either treats or diagnoses. Then there are industry standards, again, for that particular clinical condition or procedure that your device does.
State of the art (SoTA) – State of the art is also another very important source from where you can identify endpoints. Let’s take the example of state-of-the-art. Let’s go with the example of a catheter. You’re talking about a catheter that delivers a stent and therefore helps in revascularization. So, what type of endpoints should you consider and how do you make them measurable? So, for a catheter, let’s say it’s fairly simple to assume that one of the endpoints should be a safety endpoint and would be that there is limited mortality, morbidity, there’s limited dissections associated with the use of your device. So, when you say limited, that endpoint is valid, so having less dissections or having less mortality is an endpoint, but it is not measurable.
How do you make it measurable by quantifying it by saying my device has dissections in the range of say 2%, 3%, 4%. So, adding a value beside that makes that endpoint measurable and quantifiable. Something that you can demonstrate via your data. So how do you come up with these values and percentages? How do you determine if these values and percentages are acceptable? If you say 50%, your device will obviously have detections less than 50%, but is that a good claim to make? Is that something that is valid? How you can determine that is to check the state of the art. So, say you identify a benchmark device, you go through the literature for this benchmark device, and see what kind of data is available for your benchmark device. If your benchmark device has a dissection rate of 4% or 5%, you can set that as your limit for your own device. Then you can look through your data, your own clinical investigations and the literature published on your device to check if your device has dissections that fall within this rate. So, that would be a valid claim and a measurable claim. Something that you can easily demonstrate via the data that you have. Going through state-of-the-art and industry standards is a very good way of identifying endpoints and quantifying them.
Industry standards also often provide values that you can use in your claims. For example, say you are considering a device that is used for radiation therapy. There are several standards that surround what is the safe dose rate that can be dispersed by a radiation therapy device. So that value you can consider as your endpoint. Then you can say that my device safely delivers this dose rate within so and so square meters or within so and so area. The industry standards also specify certain things like what is considered accurate and precise during radiation therapy or during radiation delivery by device. So, those are things also that you can cite in your performance objectives.
You can say that my device follows industry standards, meaning it delivers radiation within this particular range. It delivers with this accuracy, with this precision, and those values can be obtained from industry standards and consensus documents. Once you have those values, you can go through your internal documents to see if your risk management documents and your internal testing, as well as any clinical investigations that you have, support these claims.
There is a scenario where you cannot have direct clinical outcomes and therefore you cannot have direct clinical claims. These come into play when you are considering indirect benefits. So, as we mentioned earlier indirect benefits are for those devices where they do not have a direct effect on the patient. They are not directly involved in either the treatment or diagnosis of a clinical condition that a patient is experiencing. So, in that case, you have two options. One is to say that your devices success or your devices safety and performance objectives can be only demonstrated through the safety and performance objectives of the main device with which it is used. For example, a device that measures blood pressure during a dialysis procedure, the actual device that measures the blood has no diagnostic value. Neither does it have any treatment value. The value entirely depends on the device that is performing the dialysis, but you can say with data that helps identify the flow rate or the access flow rate through the dialysis machine, we are able to optimize the dialysis settings and therefore deliver the best dialysis therapy to the patient. It’s helping us optimize patient management. So how do you demonstrate optimization of patient management? That is not something that will have a clinical outcome that you can measure, that is not something that will have a quantifiable number that you can measure. So, in these cases is where you use something that we call surrogate endpoints.