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Moderator: Irene Aihie

10-16-19/12:00 pm ET

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FDA Webinar: Consideration of Uncertainty in Making Benefit-Risk Determinations in 

Medical Device Premarket Approvals, De Novo Classifications, and 

Humanitarian Device Exemptions - Final Guidance

Moderator: Irene Aihie

October 16, 2019

12:00 pm ET

Coordinator: Welcome and thank you for standing by.

Today’s call is being recorded. If you have any objections you may disconnect 

at this time.

All participants will be in a listen only mode until the Question and Answer 

session of today’s conference. At that time you may press star 1 on your 

phone to ask a question.

I would now turn the call over to Irene Aihie. You may begin.

Irene Aihie: Hello. And welcome to today’s FDA webinar. I’m Irene Aihie of CDRH’s 

Office of Communication and Education.

On August 30, 2019 the FDA issued the Final Guidance Document, 

Consideration of Uncertainty in Making Benefit Risk Determination in 

Medical Device Pre-market Approval, De Novo Classifications and 

Humanitarian Device Exemption.

This guidance outlines a rigorous, methodical approach for the consideration 

of uncertainty when assessing benefits and risk of a medical device and for 
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determining when it may be appropriate to shift some data collection from 

pre-market to post market.

This includes devices subject to pre-market approval applications, De Novo 

requests and humanitarian device exemptions.

Today, Charles Viviano, Medical Officer and Clinical Deputy Office Director 

for the Office of Gastrorenal, OBGYN, General Hospital and Urology 

Devices in the Office of Product Evaluation and Quality, and Pablo Morales, 

Chief Medical Officer in the Office of Clinical Evidence and Analysis, both 

here in CDRH, will present an overview of the guidance document.

Following the presentation we will open up the line for your questions related 

to the information provided during the presentation.

Additionally, there are other center subject matter experts here with us to 

assist in the Q&A portion of our webinar.

Now I give you Charles.

(Charles Viviano):Thank you Irene and welcome to our webinar presentation of Consideration of 

Uncertainty in Making Benefit Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications and Humanitarian Device 

Exemptions Final Guidance. For simplicity we will refer to it as the 

Uncertainty Guidance from now on.

Let’s review the agenda.

We will start by identifying the objectives for today’s presentation and 

provide some background on the rationale for this guidance, where
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consideration of uncertainty fits in the overall assessment of benefit risk and 

how it supplements our perspective on benefit risk determination as proposed 

in our existing Benefit Risk Guidance documents.

We will discuss the scope of this guidance - where and when it applies and,

importantly when it does not.

We will review the factors CDRH will consider when assessing whether 

additional uncertainty might be warranted and, if so, to what extent.

We will discuss the application of the principles of the Uncertainty Guidance 

in two scenarios (breakthrough devices subject to PMA and devices for small 

patient populations subject to PMA) where greater uncertainty could be 

appropriate and we will review examples.

We will also review mitigations to account for greater uncertainty and finish 

up by providing resources for you should you need further guidance on the 

Center’s thinking on benefit risk for different submission types, in addition to 

taking questions at the end.

By the end of this presentation you should understand how uncertainty fits 

within the FDA’s benefit risk framework, as well as the factors the FDA 

considers in assessing the appropriate extent of uncertainty about a device’s 

benefits and risks.

Finally, you should understand how these factors are applied in two scenarios 

where greater uncertainty might be appropriate - breakthrough devices and 

devices for small populations.
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This Uncertainty Guidance falls within the overall benefit risk paradigm the 

Center has described for various submissions through a number of benefit risk 

guidance documents and policies. The Agency generally provides marketing 

authorization for a device when it meets the applicable standards, including 

that its benefits outweigh its risks.

Consideration of the uncertainty surrounding the benefits and risks is 

something we take into account when making the benefit risk determination 

that is part of the evaluation of a device in a variety of contexts.

For example, FDA’s final guidance on Factors to Consider in Making BenefitRisk Determinations in Medical Device Premarket Approval and De Novo 

Classifications (“PMA and the De Novo benefit risk guidance”) includes 

consideration of patient preference and uncertainty in the process of making 

such determinations and provides a framework for benefit risk decisionmaking for these submissions.

These benefit risk guidances for different submission types and this 

Uncertainty Guidance complement each other in that benefit risk guidances 

list uncertainty as a factor in benefit risk decisions, while this guidance further 

clarifies how we determine the appropriate extent of uncertainty for a device 

at the time of designing the clinical data that will be used to support a future 

marketing application.

FDA’s approach is tailored to the type and intended use of the device and the 

type of decision we are making. To provide clarity on how the FDA will 

assess for the appropriate extent of uncertainty when planning the collection 

of clinical data, we have identified factors to consider during this process.
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Doing so provides a rigorous, methodical approach for the consideration of 

uncertainty.

In some circumstances FDA may accept greater uncertainty regarding the 

device’s probably benefits and risks when appropriate because of the greater 

probable public health benefits of earlier patient access.

Further, it may be appropriate to collect additional data in the post market 

setting, rather than pre-market, to address the greater uncertainty about the 

device’s probable benefits and risks provided that the statutory standards for 

pre-market approval are met. This is the so-called “pre-market, post market 

data shift”.

The appropriate extent of uncertainty in clarifying the clinical evidence 

needed to support pre-market decisions is flexible and depends on a number of 

factors including the device type, patient population characteristics, the 

intended use of the device, and the type of decision the FDA is making,

among others.

This is not necessarily a new concept. This guidance provides a framework for 

that flexibility when determining what data collection is appropriate at the 

right time.

To better articulate FDA’s policy on its decision making in various other 

contexts across the total product life cycle, including with respect to other 

types of submissions for devices, FDA has published several guidances that 

demonstrate a flexible, patient-centric benefit risk approach, including the 

consideration of patient preferences and uncertainty.
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This Uncertainty Guidance fits within the agency’s benefit risk paradigm and 

further clarifies assessment of the appropriate extent of uncertainty when 

designing the clinical evidence needed for PMAs, De Novos and HDEs.

These aforementioned guidances take into account the uncertainty inherent in 

the totality of evidence regarding probable benefit risk. This includes 

identifying when it would be appropriate to include risk mitigations and the 

collection of post market data within its authority to address uncertainty in 

benefit risk information.

There can be varying amounts of uncertainty in benefit risk information

received by the Agency. Uncertainly can be inherent in the collection of 

clinical evidence. We identify uncertainty in the information we are given as 

arising from various sources.

There can be uncertainty around the type, magnitude, duration, frequency and 

other aspects of a device’s benefits and risks to patients. Other sources of 

uncertainty in clinical data include patients lost to follow up, missing data, 

protocol deviations, and underpowered pre-market studies without subsequent 

post market studies.

In addition the policies in this guidance further FDA’s mission to promote the 

public health by fostering medical device innovation and facilitating timely 

patient access to high quality, safe and effective medical devices by 

acknowledging and addressing uncertainty upfront.

In addition, the principles described in this guidance aim to assure greater 

transparency, predictability, consistency and efficiency using least 

burdensome principles.
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The tenets of this guidance apply to the generation of clinical evidence at the 

pre-submission and IDE stage in support of PMAs, De Novos and HDEs.

Examples provided of PMAs for breakthrough devices and PMAs for devices 

intended for small patient populations are illustrative but the application of 

this guidance is not limited to these submissions.

As stated previously, the appropriate extent of uncertainty is determined by 

many factors which we will review shortly. These factors help to determine 

whether, and to what extent, a pre- to post-market shift might be acceptable.

The pre- to post-market shift may depend, in part, on the magnitude of the 

probable public health benefit. For example, a greater data shift could be 

appropriate if the probable magnitude of the benefit is high as is the likelihood 

that the data can and will be collected in a timely manner post market.

A large data shift may not be appropriate if post market data collection is not 

likely to occur in a timely manner or at all.

The FDA has identified the following factors to provide a transparent and 

methodical approach to assess the appropriate extent of uncertainty in 

developing the clinical evidence required to support a marketing application.

The following factors are taken directly from the guidance.

First the extent of the probable benefits of the device, taking into account the 

type, magnitude, probability, duration and frequency of those benefits,

including if the probable benefits are greater than those of approved or cleared 

alternative treatments or diagnostics or the standard of care.
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This first factor is an assessment of the probable benefits of the device 

including whether the benefits are greater than those of currently approved or 

cleared alternatives.

You may notice we are talking about probable benefits here, because at the 

pre-submission or IDE stage of development data demonstrating benefit may 

not be available.

Next, the extent of the probable risks of the device, taking into account the 

severity, type, number, rates, probability and duration of those risks, including 

if the probable risks are less than those of approved or cleared alternative 

treatments or diagnostics or the standard of care. This is essentially the same 

concept as the first factor but addressing the probable risks.

The next factor is the extent of uncertainty regarding the benefit risk profile of 

approved or cleared alternative treatments or diagnostics or the standard of 

care. For example, the strength of the evidence supporting the alternative 

treatment or diagnostic.

In other words, how much uncertainty has the FDA already accepted in our 

approved or cleared treatments. For various reasons the FDA may have 

accepted additional uncertainty in assessment of benefit and risk when 

reviewing a marketing application.

For example, if the device was intended for a very sick population with few 

treatment options or for an HDE.

The next factor is patients’ perspective on appropriate uncertainty about the 

probable benefits and risks of a device, if available.
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Note, this is not assessing whether patients would choose this device over 

currently available options but, rather, what do patients think is the 

appropriate amount of uncertainty surrounding the device’s benefits and risks. 

That is how much uncertainty in benefit and risk are patients willing to 

accept?

This is typically only available in well-conducted patient preference 

information studies. For further reference please see the FDA’s Patient 

Preference Information Guidance.

The next factor is the extent of the public health need- for example, 

seriousness of the illness, benefit risk profile of other available therapeutics or 

diagnostics, if any, including the current standard of care and the portion of 

the target population for whom there would be a positive benefit risk profile.

This factor assesses the Big Picture surrounding the device and the indicated 

population (the illness, the alternatives available, who would benefit, et 

cetera.)

This factor allows consideration of multiple issues around the device and 

intended use which together may create a different perspective than any of 

these issues taken separately.

The next factor considers the feasibility of generating extensive clinical 

evidence pre-market based on appropriate considerations (for example, taking 

into account the prevalence of the disease or condition).

By means of example, perhaps all stakeholders may agree that an 

appropriately powered randomized control trial would be appropriate. But 
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given the prevalence of the disease, the patient population, and other factors,

is it likely that such pre-market clinical data collection would be feasible?

In some situations, it might be more reasonable to collect some data premarket with additional post market data if such collection post market is 

feasible and likely, and there is still enough evidence overall, pre-clinical, 

clinical, animal, et cetera, to still meet the applicable regulatory standards for 

marketing authorization.

The next factor is the ability to reduce or resolve remaining uncertainty of a 

device’s benefit risk profile post market (for example, consideration of the 

FDA’s authority to require post market data collection and the likelihood that 

the necessary post market data collection will be completed within reasonable 

timeframes).

This factor addresses as to whether there is an advantage for pre to post 

market shift. But one must also consider the likelihood the necessary post 

market data will be collected. For example, if there were already a wellestablished registry that can provide the data.

The next factor addresses the likely effectiveness of mitigations such as 

labeling and other tools to help provide a reasonable assurance of safety and 

effectiveness of the device as applicable.

Can the additional uncertainty be mitigated (given there are advantages to 

accepting this uncertainty) through labeling or further refining the indicated 

population to one that is more likely to observe a benefit or might experience 

a greater benefit than a larger population?
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Regarding labeling, where post market data collection is required as a 

condition of approval to address greater uncertainty in the device’s probable 

benefits and risks, FDA intends to consider whether it would be appropriate 

(for example, whether it would be helpful to healthcare providers) to include 

as a condition of approval that the device labeling describe the post market 

data collection and its purpose.

Where applicable, FDA also intends to include such information in the 

Summary of Safety and Effectiveness Data (the SSED) and to flag post 

market studies that are condition of approval for the device on our Web site.

The next factor takes into account the type of decision being made. For 

example, there is generally likely to be more uncertainty surrounding a 

device’s benefit risk profile based on the evidence submitted in an HDE

application as compared to a PMA because the standards for approval are 

different. And this is essentially dictated by the different policy and statutory 

requirements for certain marketing applications.

And finally, the last factor considers the probable benefits of earlier patient 

access to the device. The FDA might be willing to accept more uncertainty to 

provide earlier patient access to a device. Again, this brings into consideration 

disease, current treatments available, the population that could benefit from 

earlier access, et cetera.

Finally, similar to the least burdensome principles, consideration of 

uncertainly as described in this guidance does not lower the bar for the 

evidentiary requirements as defined by the statutes for the respective type of 

marketing application.
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The evidence supporting the device’s reasonable assurance of safety and 

effectiveness must continue to meet the applicable regulatory standards for 

marketing authorizations.

And now I will turn it over to Pablo to discuss application of the principles of 

the guidance and to review the examples provided in the guidance document.

Pablo Morales: Okay. Thank you very much Charles. So now that we know 

the background and the factors that are outlined in this guidance document we 

are going to dive into the applicability of these.

One case where increased uncertainty might be appropriate is for 

breakthrough devices because by nature these devices have the potential to 

address unmet clinical needs in serious conditions and also because patients 

may be willing to accept greater uncertainty in the benefits and risks of such 

products.

As previously outlined by Dr. Viviano, to meet the statutory standards for 

approval including that the device’s probable benefit out weigh its probable 

risks, the FDA may accept greater uncertainty regarding the device’s probable 

benefits and risks when appropriate, because of the greater probable public 

health benefit of earlier access to patients.

However, if greater uncertainty is deemed appropriate, it is critical that the 

data collected in the post market setting is reliable, high quality and collected 

in a timely manner. Therefore, certain post market controls may be necessary 

like timely post market data collection, transparency and accountability.

Now I’m going to tell you a little bit more about these three mitigation 

strategies.
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Timely post market data collection. We require a post market study as a 

condition of approval within a specific appropriate timeframe.

And second, we need to ensure that the FDA’s expectation are explicitly finetuned in the 522 orders, and in the PMA and HDE conditions of approval, so 

that the agency will have certainty that these post approval studies are going 

to be conducted in a timely fashion.

The second mitigation strategy is transparency. Under transparency we expect 

the labeling to describe when post market data collection is required to 

address greater uncertainty and also include this information in the summary 

of safety and effectiveness or SSED, the Summary of Benefit and Probable 

Benefit or SBPB or the De Novo transparency summary.

And last but not least, in the mitigation for greater uncertainty we have 

accountability. The agency will hold an advisory committee meeting if there 

are outstanding questions about whether post market data continues to support 

a reasonable assurance of safety and effectiveness.

And also, taking into account committee recommendation and post market 

data, we will consider issuing a withdrawal order or certain restrictions on the 

sale and distribution or narrow the indication for use for a particular device.

Another case where additional uncertainty might be considered appropriate is 

on devices for a small patient population that are subject to PMA because of 

the rarity of the disease or condition, it is generally not feasible or it’s also 

time intensive to generate extensive clinical evidence pre-market.
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And also, there is an unmet clinical need that is addressed by the device, such 

as there are no available therapeutic or diagnostics for that patient population.

Similarly, when a device is not eligible for a breakthrough or HDE status we 

can consider these uncertainty principles.

And last but not least, while there is not a specific number of patients that will 

be considered as a small patient population, this approach could be used for 

patients with rare disease or conditions or for patients within a clinically 

uniform subset of a broader population.

Now I’m going to go through the specific examples that were outlined in the 

guidance document. Although these examples illustrate how uncertainty may 

be reflected in the confidence level of one sided significant level for a clinical 

study, we know that uncertainly may be reflected in many other ways, when 

appropriate and based on the circumstances of the given device technology. 

For example, by using a surrogate endpoints.

With that in mind let’s describe the first example from the guidance 

document.

Example one is about breakthrough devices that are subject to PMA. The 

device is a breakthrough device that is intended to treat a currently treatment 

resistant condition. The performance goal is 70% in a proposed pre-market 

single study. And after an assessment for conventional, modest or high extent

of uncertainty, the clinical trial will be reflected by the one-sided significant 

level and will be manifested in different sample size.

So when scenario one is conventional uncertainty based up on the factors 

outlined in the guidance document that were considered into this given 
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example and all the relevant information, the FDA is not willing to accept 

additional uncertainty in the pre-market study design and the one sided 

significance is 2.5%, the observed performance goal is 74% and the spec 

sample size will be 535 subjects to be 97.5% confident the performance goal 

is above the 70%.

Scenario two is about modest uncertainty. Based on the relevant 

considerations including the feasibility of a post market data collection, FDA 

determines that modest extent of uncertainty is appropriate. And this will 

result in a larger one side significance from 2.5 to 5% and lower confidence 

from 97.5% to 95%, which will result in a smaller sample size of 385 subjects.

The approach will include a post market study as condition of approval noted 

on the Website.

Now, suppose the FDA instead determines that, based on the relevant 

considerations and the factors outlining the Uncertainty Guidance, including 

that the sponsor has a reliable and appropriate mechanism to complete a 

timely collection of post market data. For example, a registry that meets 

the criteria outlined in real world evidence guidance document published in 

August 2017 an even higher extent of uncertainty may be reasonable.

Therefore, the example by modifying the one sided significance and the level 

of confidence will result in a sample size of 125 subjects to be 80% confident 

the performance goal is above 70%. The condition of approval that post 

market study is noted in the labeling, in the SSED and on the Website, as 

appropriate.

Now, example 2 from the guidance document is about devices for small 

patient populations that are subject to PMA. The device will be intended to 
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treat a disease with an incident of 10,000 new cases annually. This is not a 

breakthrough device because the disease is not life threatening or irreversibly 

debilitating. It’s indicated for a disease that is serious but to which there are 

no available therapies and the acceptable performance goal is 60%.

So using the same approach as we did for the breakthrough devices, we are 

going to go through conventional, modest and high uncertainty.

Scenario one is about conventional uncertainty. Based upon the factors 

outlined in the guidance and all the relevant information, the FDA is not 

willing to accept additional uncertainty in the pre-market study design.

The one sided significance is 2.5%, the observed performance goal 66% and 

the expected sample size is 274 subjects to be 97.5% confidence that the 

performance goal is above the 60%.

Now, for the modest uncertainty similar to what we did with the breakthrough 

designation devices, we are going to increase the one sided significance alpha 

to 10%, we are going to lower the confidence level from 97.5% to 90% and 

the sample size resulting from this example will be 128 subjects.

Now modest uncertainty requires a post-market study as condition of approval 

noted on the Website. These pre-market to post market shift can be made 

possible if it is feasible to collect the post market data that the agency 

requires.

Last but not least the scenario 3, the high uncertainly is based upon the factors 

in the guidance document and all the relevant information that there is a 

reliable source of post market data like a registry.
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The FDA is willing to accept additional high uncertainty in the pre-market 

study with a significant pre to post market shift when the one sided 

significance is 20%, the observed performance goal is 66%. We are going to 

be 80% confident that the performance goal is above 60% and that’s going to 

take us to a sample size of 65 subject in the pre-market study.

Now, a robust post market study with reliable data source like from a registry 

needs to be in place and the condition of approval that post market study will 

be noted on the label, in the SSED and on the Website, as appropriate.

The following slide illustrates resources related to a benefit risk 

determinations throughout the total product life cycle in different 

circumstances.

So now we are going to open the line to start getting some questions.

(Charles Viviano):While the Operator is queuing up the questions one frequently asked question 

is, “Does the uncertainty guidance apply to 510(k)s that require clinical data,”

which is a small subset of 510(k)s? Because the evidentiary requirements and 

the regulatory requirements of substantial equivalence are different than for 

PMAs, De Novos and HDEs the Uncertainty Guidance as described here does 

not apply to those 510(k)s where clinical evidence is required.

Coordinator: As a reminder if you would like to ask a question over the phone lines please 

press star 1 from your phone, unmute your line and speak your name clearly 

when prompted. Your name is required to introduce your question. If you 

would like to withdraw your question please press star 2.
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Again if you would like to ask a question please press star 1, unmute your line 

and speak your name clearly when prompted. One moment as we wait for any 

questions.

(Charles Viviano):Another frequently asked question while we are waiting is, “How are patients 

likely to be affected by the principles outlined in this guidance?”

The acceptance of greater uncertainty in pre-market submissions where 

the probable benefits outweigh the probable risks may translate to more timely 

access to new medical devices by making sure our processes are efficient and 

our regulatory frameworks are tailored to technology type and patient needs.

We believe we can garner the information about the safety and 

effectiveness of new devices in the pre and post market settings with less time 

and less cost while we are providing the assurances that patients depend upon.

Coordinator: Our first question comes from (Allison Komiami). Your line is now open.

(Allison Komiami): Hi. Thank you so much for this webinar. Very, very helpful. I have got a 

quick question about the breakthrough pathway and also whether or not this 

guidance document will also encompass the Safer Technologies Program 

when that becomes finalized?

Woman 1: This is Angie Krueger, Associate Director for Regulation Policy and 

Guidance. Excuse me in OPEQ. That’s a great question. I think right now as 

you noted the Safer Technologies Program (STeP) is a draft guidance and a 

draft policy and will be looking at the intersection of that policy if it’s 

finalized and these guidances.
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You know, the Safer Technologies Program (STeP) is broader than some of 

the, you know, than the scope of this particular guidance as (Charles) noted. 

This is geared towards PMAs, HDEs and De Novos and the Safer 

Technologies Program (STeP) could be broader than those.

And so I think there are certainly things that are in the Safer Technologies 

eProgram (STeP) sort of be a final policy it would feed into this where 

considerations of uncertainty would be appropriate but they may not be a 

completely overlap to data set. And we will be looking at how that overlaps 

and how they feed into each other as we finalize the policy for the Safer 

Technologies Program (STeP).

(Allison Komiami): Excellent. Thank you so much.

Coordinator: As a reminder if you would like to ask a question please press star 1 from your 

phone. Our next question comes from (Andrea Mushen-Bourne). Your line is 

now open.

(Andrea Muchen-Bourne): Hi. What recommendations can you provide to determine how to 

balance the focus on uncertainty at the IDE level versus PMA for novel

devices?

(Charles Viviano):So, this is Charles. I just want to follow up. So I think you are asking how to 

balance the uncertainty at the time of IDE development and the uncertainty at 

the time of the marketing application for PMAs. Is that correct or did I 

misinterpret your question?

(Andrea Muchen-Bourne): Yes. That’s correct. My concern is that waiting until the PMA 

level might cause issues especially if it’s a novel device which needs to - the 

uncertainty needs to be addressed sooner.
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(Charles Viviano):Yes. And I think, you know, the Uncertainty Guidance is certainly trying to 

recognize that concern and to try to address that uncertainty earlier in the 

clinical data development phase.

This is a bit more - I understand your concern with regard to novel devices but 

hopefully identifying the uncertainty and addressing it earlier in the review 

cycle will be helpful at the time that we are at the marketing application 

because we will have made an assessment of uncertainty based upon the 

factors that we discussed this morning - this afternoon, I’m sorry, and sort of 

address those upfront.

And we will have agreed between the agency and the stakeholders with regards to acceptable and 

appropriate levels of uncertainty and their mitigations. Pablo and I mentioned mitigations for that 

additional uncertainty so that there is always going to be uncertainty at the time of the marketing 

application for reasons that I alluded to.

Clinical trials don’t always go exactly the way we all envision them to go. 

There is loss of follow up, there are other things that happen during the 

conduct of the clinical trial.

If we were able to identify and address some of the uncertainty upfront we are 

hoping that we will have a better understanding of the acceptable and 

appropriate amount of uncertainty at the time of the marketing application.

Does that help or does that answer your question?

(Andrea Muchen-Bourne): Yes. Thank you.

Pablo Morales: This Pablo. In addition to what Charles just said I want to mention Andrea 

that we account for the uncertainty as much as we can using these principles 
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under the IDE phase. At the time of PMA we want to use the benefit risk 

guidance to see if the benefits of the device outweigh the risks.

Hopefully because we are using these principles of uncertainty prospectively 

through IDEs, if there is an occasion on which we are going to require a post 

approval study and there is no registry up and running, for example the 

Electronic Health Record (her) in the institutions doing the clinical study for 

the IDE, can be all beefed up to answer the safety and effectiveness question.

I think there is an opportunity to start working with the FDA proactively so 

that when the PMA comes along we have developed the landscape to collect 

that additional uncertainty because of developing a registry take times .

There will always going to be uncertainty but I think what this guidance is

allowing us to do is to plan for uncertainty so that we have less challenges? at 

the time of PMA, number 1, and number 2 that if any post market mitigation 

strategy needs to be put in place we will start working on them upfront. Not 

the time of PMA when we don’t have time to work with industry, professional 

societies, patient reps and all other stakeholders to for example develop a 

registry.

Those things don’t fall from the sky and it takes time to build up a registry or 

a real world data source and there will be an opportunity to bridge the gap 

from the IDE phase so that when the PMA comes along you are going to have 

the certainty that the data is going to be collected and we will be reassured

that the statutory standard of safety and effectiveness is going to continue 

through post market.

(Andrea Muchen-Bourne): Thank you.
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Coordinator: Our next question comes from (Pamela). Your line is now open.

(Pamela): Hi. My question is specific to the De Novo process and I was wondering if 

you could share some best practices around providing the risk benefits 

summary to go in to the De Novo application.

(Angie Kreuger): This is (unintelligible). Thank you for your question. So I think that what we 

see in De Novos in particular because those devices have a different risk 

benefit profile than products that are reviewed under PMA. Those a low to 

moderate risk devices that could be placed in class 1 or class 2 with special 

controls if appropriate.

It’s really being able to tell your story and outline in the context of the data 

collected for the device under review how you consider the benefits and the 

risks - how the benefits outweigh the risks and how any risks to health are 

mitigated by proposed special controls.

And so I think in the context of De Novo more uncertainty is certainly a part 

of that benefit risk calculation similar to PMA. Its presented in a different way 

and the mitigation is maybe different particularly for devices that may be of 

lower risk. The way that you outline how - what the clinical benefit is and 

how the benefits outweigh the risk may differ very, very greatly in terms of 

the different types of devices.

And to some of it that I think is helpful for reviewers is really being able to 

kind of outline how you think those benefits identified how you think the risks 

are mitigated and what calculus looks like really in kind of a story form.

(Pamela): Thank you.
FDA Webinar

Moderator: Irene Aihie

10-16-19/12:00 pm ET

Page 23

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