又读了读CHTP FDA panel review summary# Stock
t*h
1 楼
抛砖引玉
14Jan2014:
http://www.fda.gov/downloads/advisorycommittees/committeesmeeti
The primary reason to not recommend approval is the lack of sufficient
evidence of
efficacy. There is only one successful trial and it is well known that
random factors can
cause erroneous clinical trial outcomes. Patients with symptomatic
neurogenic
orthostatic hypotension are vulnerable and it is important to ensure their
safety b y
protecting them from exposure to drugs that may not be effective,
particularly drugs that
have a theoretical basis for causing cardiovascular safety issues, as this
drug has.
Additionally , the lack of evidence of durability is particularly concerning
. Patients should
not be exposed to a drug chronically unless benefit is established over a
reasonable
amount of time – at least three months. It is possible that there is a down
regulation of
NE receptors in the peripheral circulation after prolonged exposure to
droxidopa. If this
is the case, one might consider approval but would need to label the product
differ ently
than what is being currently proposed (long-term use). Durability of effect
should be
studied further so that proper instructions for use can be crafted. Finally,
the safety of
droxidopa is still poorly characterized and another properly designed trial
should be
conducted to evaluate it. This development program was not properly designed
to
evaluate safety because of three factors: 1) the absence of a pure placebo
group, 2)
most of the safety data were collected in open-label trials and 3) blood
pressure was
collected with the head of the bed tilted at 30 degrees. Vasoconstriction is
the
mechanism of action of droxidopa. Therefore, without a control group, it is
logical to
assume that the cardiovascular adverse events, and there were many, were
cause d by
droxidopa. There is also the concern of neuroleptic malignant syndrome.
Since there
were some Japanese postmarketing cases that were not explicable on the basis
of
other drugs known to cause the syndrome, one needs to be concerned that
droxidopa
may cause this sometimes fatal condition.
再对比 23Feb2012
http://www.fda.gov/downloads/advisorycommittees/committeesmeeti
没觉得有什么变化
如果approval，会比较surprise
14Jan2014:
http://www.fda.gov/downloads/advisorycommittees/committeesmeeti
The primary reason to not recommend approval is the lack of sufficient
evidence of
efficacy. There is only one successful trial and it is well known that
random factors can
cause erroneous clinical trial outcomes. Patients with symptomatic
neurogenic
orthostatic hypotension are vulnerable and it is important to ensure their
safety b y
protecting them from exposure to drugs that may not be effective,
particularly drugs that
have a theoretical basis for causing cardiovascular safety issues, as this
drug has.
Additionally , the lack of evidence of durability is particularly concerning
. Patients should
not be exposed to a drug chronically unless benefit is established over a
reasonable
amount of time – at least three months. It is possible that there is a down
regulation of
NE receptors in the peripheral circulation after prolonged exposure to
droxidopa. If this
is the case, one might consider approval but would need to label the product
differ ently
than what is being currently proposed (long-term use). Durability of effect
should be
studied further so that proper instructions for use can be crafted. Finally,
the safety of
droxidopa is still poorly characterized and another properly designed trial
should be
conducted to evaluate it. This development program was not properly designed
to
evaluate safety because of three factors: 1) the absence of a pure placebo
group, 2)
most of the safety data were collected in open-label trials and 3) blood
pressure was
collected with the head of the bed tilted at 30 degrees. Vasoconstriction is
the
mechanism of action of droxidopa. Therefore, without a control group, it is
logical to
assume that the cardiovascular adverse events, and there were many, were
cause d by
droxidopa. There is also the concern of neuroleptic malignant syndrome.
Since there
were some Japanese postmarketing cases that were not explicable on the basis
of
other drugs known to cause the syndrome, one needs to be concerned that
droxidopa
may cause this sometimes fatal condition.
再对比 23Feb2012
http://www.fda.gov/downloads/advisorycommittees/committeesmeeti
没觉得有什么变化
如果approval，会比较surprise
