I think we're going to start again because my wife took the kids to the gym and I missed
the ride by about 30 seconds that's why actually the stream was still on and I was still doodling
because I was trying to figure out where the car went and then I think I just realized
that what happened was my wife took the kids to the gym which means that I can finish this
stream now as a second edition and then do something else after dinner to earn my bread.
So I'm going to go right away back to this and that means that I'll cut over here, I'll
put this one up, I'll get over to this one.
And I will head to the gym after this is over with and meet them after they're done shooting.
So they have this thing, you can look it up on the internet, it's called shoot 360 and
it's a little like workout place just for basketball and they get a half an hour of
shooting on like a rebounding machine and they also get like a half an hour of ball handling
and so they do that by themselves and then after that we play and so usually during that
hour I have a podcast in my ears or something like that and I'm shooting around on the big
gym. So it's a pretty nice place to go because it's also in this giant building that has
a full-size soccer field inside of it and so you just get this kind of very spacious
feeling, it's a giant gym with a giant place to shoot buckets and also it has soccer going
on and stuff so it's kind of like a little funny temple of sport. So that's where they
are now, I've got about 45 more minutes, I think that's all I need to finish this.
So I will escape out of here and we'll just let Uve continue to explain the subtleties
of getting an EUA from the FDA in February of 2020.
The guidance describes FDA's current thinking on this topic and should be reviewed as a
recommendation unless specific regulatory or statutory requirements are cited. The guidance
is applicable to all devices as defined under Section 201 of the Act. As you've seen earlier
in Dr. Tense's presentation, for the purpose of the guidance, real-world evidence is defined
as data relating to patient health status and or delivery of healthcare routinely collected
from a variety of sources. For example, real-world data include data derived from electronic
health records, claims and billing, data from products and disease registries and data gathered
from other sources such as mobile devices. For the purpose of the guidance, real-world
evidence is defined as a clinical evidence regarding the usage and potential benefit
or risk of a medical product derived from analysis of real-world data.
The regulatory context in which real-world evidence may be used, FDA will consider the use of real-world
evidence to support regulatory decision-making for merit devices when it concludes that the data
used to generate the evidence are sufficient quality to inform a supportive, support a particular
decision. Real-world data may potentially be used as some or all of the evidence necessary to
understand medical device performance at different points of the total product life cycle. For
example, real-world data may be used to generate hypothesis to be tested in appropriate clinical
study or be used as evidence for expanding the labeling or to include additional indications for
use. I would like to mention the guidance does not change FDA's standards for regulatory decision
making and in each context we will evaluate whether the available evidence is of sufficient
quality to address the specific. So I assume that he's going to be evaluating it when it comes to
EUAs that he himself has granted and that's where I think this regulatory scheme starts to become
incredibly sketchy because you might think that there might be an ACIP equivalent here but there
isn't there's just this one guy who they sheriff and a maybe a couple equivalents that are able to
give EUAs they make the decision and the context in which that decision could be made is solely
dependent on what he considers good and if it's all real-world data that he makes that decision on
all the better clinical studies can now be based on real-world data that includes data from medical
devices, mobile devices, disease registries and electronic health records. Do you see how a national
security priority could really streamline the use of an electronic health record to cross-reference
and verify a disease registry or cross-reference or verify mobile device data? Do you see where
a national security priority event could put a German-speaking American guy in front of you
telling you that he is the firewall between you and a wholly fraudulent set of diagnostics being
used to create the illusion of a pandemic? This is our firewall right here, this guy
and his angry presentation that he's being seems to be forced to being given right now. It's
extraordinary regulatory decision being made.
So what are the characteristics for real-world data to support particular regulatory decisions?
Please note that the FDA does not endorse one type of real-world data over another.
They're all the same. They're all great. Assess the reliability and relevance of the source
and the specific elements to determine whether real-world data sources and the proposed analysis
can generate evidence that is sufficiently robust to be used for a given regulatory purpose.
The primary factors FDA considers are assessing the reliability of data include data approval
that is how the data were collected and data assurance that is whether the people and processes
in place doing data collection and analysis provide adequate assurance that errors are minimized
and that the data quality and integrity are sufficient.
Real-world evidence might be used in support of regulatory decision-making in several situations
as listed here. For more detail in all of the
sections, I refer to section six of the guidance.
So before I end, I have two slides where I want to address a couple of questions,
common questions from sponsors which plan to transition an EUA IBD product to a full market
application. The first question is, can I use the analytical and clinical data obtained for an
EUA authorization? The answer is yes, if new modification to the device has been made since
the authorization. However, if modifications have been made, then the risk assessment of the
modification will be required to determine to which extent the changes to the device would
influence its performance. For clinical data, it's important to assure that the comparator
method used to determine the truth of the specimen is still viewed as an acceptable
preference method. And the second question, can I use generated the data outside of the US
for my FDA submission? The answer here is yes as well provided that the test procedure and
performance, the test procedure was performed according to the package insert with no deviations.
We encourage sponsors to contact early, as early in the development for questions
concerning the use of EUA data to support marketing submissions.
The last question, can real data be used to help support the advancement of EUIBD products
through full marketing status? As stated in the guidance, I just reviewed
under the right conditions, yes. Data derived from real-world sources
that potentially be used to support regulatory decisions. And under the right conditions,
real-world data and associated real-world evidence, they constitute valid scientific evidence
depending on the characteristics of the data. As I mentioned earlier several times,
we encourage sponsors to contact us early in the development for questions concerning data to support.
So data derived from real-world sources becomes validation. That's what we're doing here now.
We're allowing these EUA devices to be rolled out and then for them to collect their own data,
report their own results, call it real-world data and be a source of validation for a market
approval submission. And it's as simple as that. He's telling you exactly how it's done. Yes,
it can happen. This is the way it's done. This is where the reliability has to be feigned.
This is where these are the benchmarks that you need to meet. That's what he's saying.
It's extraordinary.
Marketing market applications. This is my last material slide.
I want to thank my division, the whole staff of my division of the Division of Microbiology
Devices. Everybody is one way or the other involved in EUAs. And I would like to especially
acknowledge the individuals listed here because they have performed the heavy lifting in most of
the EUAs that we have seen. All those thanks to OC and OCC for their continuous help as well as
to our colleagues from SIBO who have helped us with standards which you will develop.
These are the individuals who make EUA happen. They have stand up to any call of an emergency
and they have worked tirelessly over weekends to make these devices available to the public as
fast as possible. Thank you.
Tirelessly over the weekend.
And so that guy was essentially what he said was that he is the head of all the EUA because
this whole division of microbiology devices is EUAs, this whole department. So the division
of microbiology devices, isn't that an interesting division to be the head of for 20 years?
To get three houses for heading to not lose your accent?
Really wanted to thank everybody. It's good that we've got incredibly good time
for making out your critical positions, isn't it?
As a note to the Office of the Chief Scientist for actually being able to help facilitate a lot
of this work in the medical device innovation consortium where we could actually get a conference
together in very short time. So Frank Whitehold in particular has been in short time.
The ladies that started the conference said that they've been organizing this for months.
What is he talking about? Is that a short time to him?
Incredibly important in actually helping do a lot of the background work that is
helping facilitate hopefully the future for the collection of rural evidence.
And so to go on with Dr. Shur and Dr. Stenzel we're actually talking about
just let's drill down just a little bit more in the rural evidence and fundamentally
while he wants to drill down the real world evidence.
There was a 21st Century Cures initiative and we had the FDA reauthorization act
which led to Meduva for commitments actually to help get pre-imposed market information
to support regulatory decisions across the breadth of which.
That was a mention of something very important.
The 21st Century Cures initiative.
21st Century which led to Meduva for commitments actually to help get pre-imposed market information
to support regulatory decisions across the breadth of which it could pop.
A huge amount of real important legislation that underlies the possibility of pandemics.
Being executed in the way that they were executed this time is found in the 21st Century Cures
Act and initiative. And I strongly recommend that everybody look into that if you've never
heard of it before. I am a little bit less informed about this one that I am about prep
and about the National Vaccines Act but this one is essential and it's a part of this stepwise
move toward the prep act. And so I need to read into this as well but it's interesting
that he mentions that one as being pivotal.
Completely used. And underneath that the medical device innovation consortium has the
national evaluations system for health technology to help develop a space where real
evidence could actually fundamentally be used. Now in the Center for Devices and Real Logic Health
we actually have a strategic priority to do this and part of the strategic priority was
this guidance that that Uva just talked about which is a cross-center harmonized effort.
Now again you're probably going to see this many times throughout the day but
that context of collecting information from a real clean health care setting.
Obviously that information if it's going to be collected it's going to have to be analyzed to
be able to be used in the context of valid scientific evidence. Now what are we talking about?
In the traditional setting you know obviously many of you are familiar with the fact that
studies are designed and they're conducted and analyzed. And then when those devices go out to
market I please note the context here that an ID is probably not necessary in every single
situation. In some cases it might be and I would refer to the Rural Evidence Guidance
to actually provide the context for that but when those devices actually get to market
or get to actual use in a health care setting they begin to help generate data.
Then that data when it's generated is done in a natural health care setting and then the question
is how can we collect and analyze that information so it can actually be useful. And so this is an
unprecedented shift in the way we think about medical records and medical data and they are
shifting it at a very opportune time right before the pandemic starts when we're going to grant 200
plus EUAs for diagnostics that could actually be the data collection that could be reflected back
on the nationwide electronic medical records etc. They are talking about a national
security priority here right this is a national security priority and so all of this talk about
what to do with the data and how to collect it has built into it these national security priorities
which may actually lead to them doing things that they wouldn't otherwise do collecting data that
they wouldn't otherwise do and interfacing with electronic medical records in a way that they
wouldn't otherwise do in order to facilitate a national security priority of moving more EUA products
to full market approval I can't write worth a damn when I'm actually talking while I write and
trying to write what I'm saying because then I try to write too fast so what does this say moving
more EUA products to full market approval I should write that without so such scribble scratch here
but that's the national security priority that has been ascribed to the entire seminar
I'm so glad I got to close this out with a little bit of a of a closer here because it's really
this is really summarizing the last three the last three so well as we looked at this seminar from
February 3rd 2020 what we are seeing is that the national security priority is not the safe and
effective products that are rolled out but it is getting more EUA products to successfully get
to full market approval using this shift from having to go through a pre-market submission system
to being able to use real world evidence gathered during the EUA stage to get through the approval
process without having to go through all this pre-market submission stuff
replacing what was required in a pre-market submission as outlined by Louvay sheriff that includes things like
that includes quality control that includes precision that and now can instead be substituted
within silico evaluation and no full validation is required and and that means that all of these
things can in theory get through with real world evidence that has been misconstrued as validating
their effectiveness and that is a very dangerous place to be had February 3rd 2020 February 3rd
it hasn't even started yet and we're already throwing all regulatory systems out of the out of the
out of the window and having a german national with a thick accent explained to us how we can
circumvent the traditional methods of pre-market approval before full market approval of the FDA
by getting an EUA and doing everything with real world data that can even include things as mundane
mobile device data never mind data from other EUA products right which could also be used to
evaluate whether or not the virus was there and so then one EUA product is validating the
effectiveness of another EUA product don't you see it holy cow it's amazing in that space
fundamentally we need data quality data quality is a very important key yeah it's all processed
data quality understand what the information is inside of a health care system exactly how
are you going to be able to use it now this question is the common question
that really drives the next statement of what is valid scientific it's fundamentally so per
our regulations you can submit anything you want to but fundamentally we can only rely on
valid scientific evidence and to be a little more clear about what valid scientific evidence could
be it really is a very broad breadth and range um well controlled investigation parcel controlled
studies objective trials and even reports of significant human experience if it can actually
be determined that you know by qualified experts that there's reasonable assurance
of safety and effectiveness that are real world personal experience can also be used to evaluate
the effectiveness of an FDA device here he just said those words you want to hear him say him again
I'll roll it back half a second now information
objective trials and even reports of significant human experience if it can actually be determined
that you know by qualified experts that's impressive there's reasonable assurance
to say from the fact that information that's impressive that's impressive and has been used
support regulatory decisions it doesn't always follow the traditional space but certainly
it's noted that things that are weird really can't be used as valid scientific evidence is it's not
logical a rationality section kind of be taken into place so what is not regarded as valid
scientific evidence is your isolated case reports are random experiences um if you don't have enough
detail around it how do you actually use utilize that information this is where the key comes in
so all we care about the end of the day is information that's fit for purpose and the appropriate
yes he did of a particular setting so we're talking he did he said weird things we don't use
weird things weird things are not generally scientific but you know it's a individual evaluation
basis talking about information that's relevant and reliable we have to be able to make a determination
fundamentally that the benefits outweigh the risks and that we can actually utilize that
information and throwing in a little extra complexity into that setting of course is that we try to
make sure that patients information is properly protected so we have harmonization for that
information it does become a little more understandable at how you can actually navigate patient
protection information and get high quality information out so in the rural evidence space
now he's using very big words to describe how they are going to try to protect people's personal
data while using it to evaluate EUA devices I don't think you can hear it any other way he
used the phrase here at the bottom information harmonization do you know what that is that's got
to be the the interface between an electronic medical record database and the database of a
pharmaceutical company the database of a social media company interfacing with the data from a
electronic medical medical record database would be information harmonization and talking about
how to anonymize make all anonymous the data or to protect people's personal data
is precisely what you would talk about if you intended to use a national security priority
to allow people to create information harmonization when that would no way shape or form be allowed
under the normal laws governing medical data and its use
that's why he has to use these big words and talk with such obfuscating sentences because
he doesn't tell you want everyone to understand it does become a little more understandable
at how you can actually navigate patient protection information and get high quality
information out so in the rural evidence space the HIPAA privacy role is how we operate for
helping protect that information and the understanding that not everything in the research space is
covered under under HIPAA that the access and use for the common role helps provide a little
additional context there but that being said information in the rural setting has been used
in many different spaces there for indication expansion for new indications for condition of
approval in both a pre-market and post-market setting and all these slides will be available
online if you want to do a deep dive but there has certainly been information collected from
multiple different venues and the point is please be creative and don't limit yourself
to that information. The perfect example which I think may have a degree of applicability
in this setting in particular is the note of an ability to actually utilize a publicly maintained
database when we actually partner together what was able to happen here in the next
chance sequencey space and I think that something that could be replicated in an EUA space next
gen sequencing appropriately set up is in lieu of full traditional studies what we're able to use
is information directly harvested from a publicly retained a publicly maintained database because
there was collaboration that happened up front between the sponsors between the database folders
and between FDA and when we actually partner together to get interoperability for that data
and establish appropriate quality checks which are achievable it was achievable in this case
and it'll be achievable in the future we can actually work together if you have questions
about real-world evidence there is actually an email address if you don't want to contact
the divisions directly you can you can email c3h clinical evidence at fda.h just.gov and if you
want to learn more about some of the public private partnerships you can contact c3h clinical
evidence at fda.h just.gov or if you want to learn more about shield in the diagnostic space you can
contact me thank you so thank you to all of the fda colleagues for sharing the fda perspective
today I think it sets a wonderful foundation for our discussions today and I look forward to
your engagement throughout the day as well we're going to take a break now and I'm going to make
a deal with you you guys silence your phones I'm hearing some phones and I promise we'll work
on getting those technology smoothing up here how's that for a deal wow so they're done that
was the end of that one and that's fine I knew it was not the much left because I didn't want to
leave it till after practice and then have to do that so we are still here ladies and gentlemen
at the same place where we have been for a very long time
oh I didn't mean to do that I apologize
you like that thing though I don't think it's that bad it actually looks pretty good that's also
render forest you know render forest is kind of fun so that was the last part of the market seminar
we won't do that one anymore I've taken my notes I've got my stuff I've got a lot more work to do
on Uve Sheriffs patents and some of the country companies that he worked for and we're going to
look at I'm going to look at some of his publications and try to decide if it's possible that maybe he
was doing more than just giving out EUAs maybe he was involved in the Human Genome Project or
in collaboration with companies that were involved in the Human Genome Project and
that might give us a clue to why he was in charge of giving away diagnostic EUAs
and and why it would be that EUAs would be given away by single people or by some weird
division called microbiome microbiological devices which is a very bizarre thing
so thanks for coming back for the last half hour if you missed it live thanks for coming back and
checking it out I will try to be on later this evening and later this evening I've got at least
a list of 20 or so things that I could cover and so we'll just see which of these pending
sort of study halls that is necessary to do that I'll do at eight o'clock and I'll see you then
thanks very much for coming and we'll be back soon