[Music]
welcome to another med cram kovat 19
update this update is for April 30th
2020 and we're also looking forward to
our first live webinar today 4:00 p.m.
Eastern Time
1:00 p.m. Pacific time if you're in the
UK that'll be 9 p.m. in India that'll be
1:30 in the morning and in Sydney
Australia that'll be at 6 o'clock in the
morning and during that webinar we're
gonna be talking about the
pathophysiology the epidemiology
diagnosis and treatment of kovat 19 we
will see you there for that this is
gonna be a little bit more of an
abbreviated update and we're going to
talk about the news of the day which of
course is REM de severe so this article
was published on April 29th 2020 in The
Lancet and it's a study out of China at
ten hospitals let's talk about the
findings in this REM de severe study
they actually wanted to include many
more patients than they were able to and
part of the reason for that was the
pandemic in China was brought under
control so quickly that they were unable
to recruit the number of patients in
their study so that's the first thing
that you should know about this study
the second one is that anybody with
symptoms up to 12 days old were able to
be enrolled in the study the two end
points in the study was number one time
to recovery and number two mortality and
we have the REM des aver and the placebo
group
now there was 237 subjects in the study
and the time to recovery in the REM d
severe group was 21 days and in the
placebo group it was 23 days and this
was not statistically significant the
mortality in the REM death severe group
was 14% and in the placebo it was 13%
again not statistically significant and
so this led the authors of the study to
say no statistically significant
benefits were observed for REMS
severe treatment beyond those of
standard of care treatment our trial did
not attain the predetermined sample size
because the outbreak of kovat 19 was
brought under control in China further
studies of REM de severe including
earlier treatment in patients with cope
at 19 and higher dose regimens or in
combination with other antivirals or
SARS cough to neutralizing antibodies in
those with severe kovat 19 are needed to
better understand its potential
effectiveness so this was a
disappointing result now interesting on
the very same day April 29th the NIH
released this news article NIH clinical
trial shows REM de severe accelerates
recovery from advanced kovat 19 this
news article is referencing a United
States study that was looking at the
same medication so let's talk about the
results of this study
this was the adaptive kovat 19 treatment
trial in the United States otherwise
known as a CT T and they did their power
analysis to try to figure out how many
subjects they would need in their study
to show statistical significance and the
number that they came up with was 1063
but as with all the trials of this size
they do something called the data safety
monitoring board looks at the study
before it's completed sort of halfway
through or even before that and they do
an interim data analysis and the reason
why they're doing that is because there
may be a possibility that this
medication may have a stronger effect
than the power that they have estimated
and if that's the case if there is an
endpoint that has already been met it
would be unethical to subject further
subjects in the study to placebo when
they could be getting the actual
treatment and so that's exactly what
happened they met on April 27th they
looked at the data and they alerted the
study coordinators that there was an
endpoint that was met so let's go over
the results here they have exactly the
same endpoints time
to recovery and mortality in the REM
death severe group the time to recovery
was 11 days in the placebo it was 15
days and the p-value here was less than
0.001 now if the p-value is less than
0.05 then that means there is
statistical significance and that is the
reason why the data safety monitoring
board decided to alert the study
coordinators that an endpoint had been
met now when we look at mortality the
mortality on the REM the severe group
was 8.0 percent and in the placebo group
it was 11.6 percent the p-value here
however did not reach statistical
significance but boy it almost sure did
0.059 remember that they stopped the
study early if the study had gone to
completion this very well might have
reached statistical significance so
given that if the results were good
enough to halt a study the questions are
is this enough
to get people on REM deseve and that's
exactly what they're looking at right
now they are doing what is called an
emergency use application or a eua
and the FDA is working with Gilead to
see whether or not production can be
ramped up to make enough REM de severe
to be used clinically in our nation's
hospitals but the question is is how
effective is this medication REM desu
aver and so something that's a
reasonable thing to look at is the
number needed to treat to get an
endpoint in other words how many people
with kovat 19 would you need to treat
with REM be severe to save one person's
life and the equation for that is the
number needed to treat is equal to 1
over the absolute risk reduction now the
number needed to treat is a situation
where if you have a low number a number
closer to one that shows that the
intervention is very powerful for
instance
somebody falling out of an airplane if
you were to give them just one parachute
how many people would you need to treat
jumping out of an airplane with a
parachute to save one person's life and
the number there of course is one
because it's a very powerful and
effective treatment and this number can
go all the way up to 50 60 100 even past
that and depending on certain
cardiovascular medications and the
population that you're talking about
these numbers can range anywhere from 10
to 2230 up to 50 and above and so the
absolute risk reduction here is 11.6
percent minus 8% which gives us 3.6
percent but we need to put it
numerically as 0.036
and when we do that the number that we
come up with is 28 so we would need to
treat 28 people with kovat 19 that come
into the hospital with Renda severe to
save one person's life if you want to
learn more about biostatistics the
number needed to treat there is more
information and we have a video at med
cram comm if you also want to learn more
about REM de severe and its mechanism of
action please check out kovat 19 update
number 33 we look forward to seeing you
at the webinar where we will go over
more comprehensively the treatment as it
stands now for Kovan 19 thanks for
joining us
you
[Music]