Hello Roberto, This is a really interesting point. I had that question come up to my mind as I was watching the lecture. With some research I found a clear answer to that concern on the FDA website. A device is considered significant risk device if it meets any of the points in this list provided by FDA. Here is the list

"• Is intended as an implant and presents a potential for serious risk to the health, safety, or
welfare of a subject;
• Is purported or represented to be for use supporting or sustaining human life and presents a
potential for serious risk to the health, safety, or welfare of a subject;
• Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease,
or otherwise preventing impairment of human health and presents a potential for serious risk
to the health, safety, or welfare of a subject; or
• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject"

If it doesn't then it is considered a non-significant risk device. They also list who makes the decision. They state that the sponsor first makes the decision unless FDA has already decided that the device is considered significant risk. All the sponsor's decisions are reviewed by the institutional
review boards (IRBs) to make sure that the decision is made correctly and the FDA is available to aid their judgment.

Reference

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf

I agree with the above post but, I think the criteria in general have to be further explained. If you look at the requirements from the site all of them say "serious risk". This brings up the question in the original post asking what qualifies a "serious risk". Also what makes something serious as opposed to not serious? What's interesting is that the sponsor actually decides what is classified as a "serious risk" and then obviously the FDA does their investigation and has the final say. I think a "serious" risk would be something that can potentially cause harm in the body. This can be from any injuries to any body components or creates some sort of morphological change within the human body. I'm sure you guys can think of more risks that are involved, those two were the two that came to my head first. But, I guess anything that has some sort of adverse reaction or has the ABILITY to create an adverse reaction would be classified as a "serious risk". And then obviously, clinical trials would need to be performed to discover and eradicate those adverse reactions. On the other hand, something that doesn't affect the body in any way would be your non-serious risk devices.

Tell me what you guys think. What are some other potential risks that you can think of?

Basically significant risk devices are to be use in supporting human life and present a potential risk to the patient's health. The potential harm to subjects could be life-threatening, could result in permanent impairment of a body function or permanent damage to the body structure. for example dental implants which required clinical trials. In contrast, non significant risk devices are the ones that doesn't represent any risk to the patient's health for example dental laminates which are porcelain veneers to create perfect smiles.

In regards to the FDA guidelines posted by la82, I tend to personally agree with their overall classification of devices into SR and NSR classes. In addition, I would like to highlight that the decision boards pay special attention to HOW the device is proposed to be used in addition to the actual device. The intended use of a device could change the determination from NSR to SR depending on any potential of lasting effects of a NSR device. For example, standard daily contact lenses are a NSR device as they pose no direct risk to the body. However, long term, overnight contact lenses are classified as SR devices because of this intended use poses potential for serious harm to the subject.
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf
http://www.eandireview.com/index.php?option=com_content&view=article&id=195&Itemid=149

From the information I found a significant risk device is one that can present a possibility to affect the health, safety or well-being of an individual. These are often class II or III devices such as sutures, pacemakers and various implants. Non-Significant risk devices, however, do not have the possibility of causing a life- threatening risk to the individual. These can include catheters or contact lenses.

Source: www.childrenshospital.org/~/media/.../SR%20or%20NSR%20Device.ashx

We can have better understanding of the "significant risk" by reviewing the FDA's requirement to review all the adverse events. The medical device reporting regulation states that a serious injury is one that is life threatening, results in permanent impairment of a body function or body structure, and makes necessary medical/surgical intervention. Many companies often neglect the latter aspect and focus on if the patient died or was injured. However, MDR requires you to report if there was a medical/surgical intervention to prevent death or serious injury.

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/ucm2005291.htm

Going of la82's post, I think the way the FDA defines the line between a device of significant and non-significant risk is blurry. I think this guideline especially raises a few concerns:

• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject”

It's a blanket statement and quite vague in what constitutes significant risk. The borderline between significant and non-significant devices should be clear. For example, what should glasses be classified as? They are an extracorporeal device and you can argue they pose a non-significant risk because of that. But should they fail, the person wearing them would lose their vision to some degree and potentially harm themselves. Even though the event occurs indirectly of proper function of the device, should the possibility of such harm make glasses be classified as a medical device that poses significant risk? I believe the line isn't as clear as it needs to be based on the description you provided.

Hi Roberto,

it really depends on how invasive the device may be, which will categorize the medical device. For example, the implantation of coronary stent is more invasive and is a "riskier" device when compared to band-aids for example. Essentially the classification of devices depend on the potential risk it has to the patients's health.

Chris

My understanding of it is, that it depends on case to case bases. It depends what your drug, device, or both intend on doing. Keep in mind, some risks may not appear in short term clinical trials. Or they may not be significant risk given the time frame to determine if they are significant. For example, they may not be considered significant risks at the time of reporting, but what about two years from the clinical trials? If clinical trials only show data for 1 year and declare it not significant risk but in practical use, the device or drug may show significant risk after 2 years of being exposed to the body environment. What happens than?

So to further push the discussion and briefly answer your question based on my understanding, I would depend on your case study, and data provided. In some cases, the FDA may require a longer term of research done to determine the risk.

Significant risks I believe are risks that would leave a permanent and unintended complication to a patient after the use of the device. It all comes down to what is deemed as acceptable risks by the FDA and the patient using the device as it is unlikely it would be used on someone without their consent. Therefore the line between significant risk and non-significant really depends on the device and the person using it.

Also, I agree with tn58 in terms of the long term risks. Procedures may work in the short term but what about the long term? In terms of the surgical procedure of a hip implant, there is a significant risk in the surgery and will most definitely require clinical trials. But this is an acceptable procedure now in spite of the risk of infection, implant failure, or even surgical malpractice. The procedure itself is actually very successful in most cases but there is also a serious risk of stress shielding from metal implants causing weak and brittle bones in the long term. This procedure is most commonly done on elderly patients who most commonly do not live long enough for this risk to be an issue, but what about for younger patients? This again goes back to the idea that significant and non-significant risks are dependent on what the FDA or the patient say is acceptable.

This is a good question where it brings up the issue where the definition for significant risk is relative. There may be varying perspectives in the proper definition of the term and this can cause an argument on the possible drawbacks of the device. However, despite the relativity in reality, the true perspective definition that controls the flow of things is the FDA’s. They are the decisive force on what qualifies to be a significant risk for a user. In my opinion, significant risk refers to physically disabling drawbacks and condition-worsening effects posed by a device. The product must be evaluated with these “risks” in order to see whether or not placing the product in the market where customers can use it would be practical. The regulation must check whether or not the drawbacks of the device are acceptable. Also, during the clinical trial phase, when these problems are diagnosed, solutions must be presented in order to improve the device.

I think this is a good question and agree that the definitions provided are vague. However, I think that it makes sense for the definition to be vague and the line between significant and non-significant risk to be slightly blurred. This could be frustrating for many of us that there isn't a clear cut answer but this is why these decisions are looked at my multiple people, the sponsor, IRB, and FDA. As someone mentioned earlier, what about glasses, the wrong prescription could alter morphology of your eyes but that would not require a clinical trial just a change in prescription. If the classification of a product that provides significant risk becomes too specific then products could be overlooked that may need a clinical trial or should be considered to have significant risk. I think that most of what the FDA deems to be a significant risk is correct in combination with people using their judgement to make these classifications. Although the last point on the list "• Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject” could be confusing because the point of this checklist is to see if the product has significant risk. This could be where some of the other views mentioned in the forum on what significant risk should be could help with making the boundaries clearer.

I think to add to the discussion of significant risk (SR) versus non-significant risk (NSR) it is useful to read about the considerations that the FDA suggests to the IRB for SR and NSR determination. I got the below information from a guideline from the FDA. Below are the three main considerations listed in the document.

1. Risk determination is based on the intended and proposed use of the device and not the device itself.

Ex. Daily wear contact lenses that are worn regularly are considered NSR by the FDA. A study for extended wear contacts that are worn overnight is considered SR. This change in intended usage results in a "potential for injuries not normally seen with daily wear lenses".

2. SR studies are necessary for any device in which the intended usage can "present a potential for serious risk to the health, safety, or welfare of a subject".

Ex. Pacemakers are necessary to sustain human life. Therefore any changes to a pacemaker that is already commercially available, whether it be "new leads, batter pack, or software", is SR.

3. If an additional procedure is needed as a part of the investigational study such as a surgical procedure, the potential harm of the procedure must also be considered.

Ex. "An investigatonal stud of a sensor pad that can detect the electrical activity of the spinal cord may be NSR if the following are true: it is done at the "same time as an already planned surgical repair of the spinal cord", the sensor does not "present a potential for serious risk to the health, safety, or welfare of a subject"
, "the sensor pad is not implanted", and "the pad is not of substantial importance in diagnosing, curing, mitigating or treating disease".

Overall, I found the consideration process for determining SR versus NSR helped clarify to me some set guidelines between the two and I thought it would contribute to the overall understanding in this forum. However, in the sensor example it stood out to me that the pad is SR if it is "of substantial importance in diagnosing, curing, mitigating or treating disease". Upon further thought, it is apparent that it is risky to do a study to prove something can treat a disease because people rely on that to treat them then.

However, this made me wonder what the difference between a SR and NSR study is and what additional considerations must be taken into account in a SR study. Does anyone know anything about this?

Resource: https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf

In response to my last post, I found sponsor responsibilities after the significant risk (SR) versus non-significant risk (NSR) determination.

If the IRB decides a study is SR, the sponsor must:

Submit IDE to FDA
Not begin the study until the FDA approves the IDE and the IRB approves the study
Comply with IDE regulations and informed consent and IRB regulations.

If the IRB decides a study is NSR, the sponsor must:

Comply with "abbreviated IDE requirements" and informed consent and IRB regulations.

IDE is an investigational device exemption that "allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data". The following link provides an entire list of IDE responsibilites:

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm046702.htm

I find it vague that the difference between a SR study and NSR study is "comply with IDE regulations" versus "comply with abbreviated IDE requirements". Does anyone have any commentary on this or experience with it? According to the wording it seems like both need to follow IDE responsibilities so why is being classified as a SR device a lot harder to pass through?

Resource: https://cphs.berkeley.edu/checklists_worksheets/nsrdevice.pdf