DOAJ (DOAJ: Directory of Open Access Journals),
Journal Year:
2022,
Volume and Issue:
25(10), P. 730 - 734
Published: Oct. 20, 2022
Bayesian
statistics
is
an
approach
for
learning
from
evidences
as
it
accumulates,
combining
prior
distribution
with
current
information
on
a
quantity
of
interest,
in
which
posterior
and
inferences
are
being
updated
each
time
new
data
become
available
using
Bayes'
Theorem.
Though
frequentist
has
dominated
medical
studies,
been
more
widely
recognized
by
its
flexibility
efficiency.
Research
development
(R&D)
anti-cancer
drugs
have
so
hot
globally
recent
years
spite
relatively
high
failure
rate.
It
the
common
demand
pharmaceutical
enterprises
researchers
to
identify
optimal
dose,
regime
right
population
early-phase
R&D
stage
accurately
efficiently,
especially
when
following
three
major
changes
observed.
The
anticancer
transformed
chemical
biological
products,
monotherapy
combination
therapy,
study
design
also
gradually
changed
traditional
way
innovative
adaptive
mode.
This
raises
number
subsequent
challenges
decision-making
early
R&D,
such
inability
determine
MTD,
deal
delayed
toxicity,
response
dose-response
changing
relationships.
because
above
emerging
that
getting
attention
industry.
At
least,
decision-making,
could
potentially
help
achieve
higher
efficiency,
shorter
period
lower
investment.
expounds
application
drugs,
compares
analyzes
idea
scenarios
statistics,
aiming
provide
macroscopic
systematic
reference
all
related
stakeholders.
.【中文题目：贝叶斯方法在肿瘤新药早期临床研发中
的发展与应用】
【中文摘要：贝叶斯学派是通过综合未知参数的先验信息与样本信息，依据贝叶斯定理，求出后验分布，根据后验分布推断未知参数的统计方法。相比频率派，贝叶斯学派更加灵活、高效。肿瘤新药是全球研发的热点，但同时也存在高失败率的风险。在肿瘤新药早期研发中，高效寻找最佳剂量、优势人群、估计疗效和成功率是医药企业和研究者的共同需求。近年来，肿瘤新药研发呈现化学药物生物制品转变、单药治疗向联合治疗转变、传统设计向创新设计转变等新趋势；伴随出现的各种挑战，包括无法找到最高耐受剂量、延迟毒性、延迟反应、剂量疗效关系变化、剂量组合众多等。基于贝叶斯方法，恰当借用先验信息，能有效帮助企业在肿瘤早期研发中，实现从传统研发模式（高投入、长周期、低效率）向现代研发模式（低投入、短周期、高效率）的转变。研究还进行了贝叶斯方法在肿瘤新药早期研发的进展阐述，与频率派的理念、应用场景的比较分析，可为医药研发的所有从业人员提供宏观、系统的参考。
】
【中文关键词：早期试验；贝叶斯；
统计设计；肿瘤】.
BACKGROUND
Early
phase
dose-finding
(EPDF)
trials
are
crucial
for
the
development
of
a
new
intervention
and
influence
whether
it
should
be
investigated
in
further
trials.
Guidance
exists
clinical
trial
protocols
completed
reports
SPIRIT
CONSORT
guidelines,
respectively.
However,
both
guidelines
their
extensions
do
not
adequately
address
characteristics
EPDF
Building
on
checklists,
DEFINE
study
aims
to
develop
international
consensus-driven
(SPIRIT-DEFINE)
(CONSORT-DEFINE).
METHODS
The
initial
generation
candidate
items
was
informed
by
reviewing
published
reports.
early
draft
were
refined
through
review
grey
literature,
analysis
real-world
examples,
citation
reference
searches,
expert
recommendations,
followed
two-round
modified
Delphi
process.
Patient
Public
Involvement
Engagement
(PPIE)
pursued
concurrently
with
quantitative
thematic
participants’
feedback.RESULTS
survey
included
79
or
SPIRIT-DEFINE
(n
=
36)
CONSORT-DEFINE
43)
extension
items.
In
Round
One,
206
interdisciplinary
stakeholders
from
24
countries
voted,
151
voted
Two.
Following
One
feedback,
one
item
added
Of
80
items,
60
met
threshold
inclusion
(≥
70%
respondents
critical:
26
SPIRIT-DEFINE,
34
CONSORT-DEFINE),
remaining
20
discussed
at
consensus
meeting.
parallel
PPIE
work
resulted
an
lay
summary
toolkit
consisting
template
guidance
notes
exemplar.
CONCLUSIONSBy
detailing
journey
decisions
undertaken,
we
envision
that
this
will
enhance
understanding
help
researchers
future
guidelines.
allow
investigators
effectively
essential
present
reports,
thereby
promoting
transparency,
comprehensiveness
reproducibility.
RegistrationSPIRIT-DEFINE
registered
EQUATOR
Network
(https://www.equator-network.org/).
Canadian Journal of Physiology and Pharmacology,
Journal Year:
2023,
Volume and Issue:
101(10), P. 529 - 538
Published: June 26, 2023
No
data
in
the
literature
have
evaluated
sex
hormone
dose
escalation
for
treating
abnormal
sleep
of
ovariectomized
rats-nor
studies
on
role
hormones
GABA
synthesis
rats'
sleep-related
areas.
The
main
aim
this
study
was
to
determine
maximum
tolerated
(MTD)
estradiol
(ET),
progesterone
(PT),
and
mixture
both
(EPT)
restore
normal
a
model
menopause
rats.
second
purpose
describe
vitro
activity
glutamate
decarboxylase
(GAD)
brain
areas
presence
or
absence
hormones.
A
weekly
dose-escalation
design
ET,
PT,
EPT
implemented
rats
(six
per
group).
Dose
continued
until
at
which
100%
exhibited
state
"complete
somnolence."
Doses
that
were
not
toxic
did
show
side
effects
considered.
For
experiments,
separated
incubated
with
radiolabeled
glutamate.
Estradiol
(17β-E2),
(P),
pyridoxal
phosphate
(PLP)
added
assay,
GAD
determined.
Under
same
conditions,
test
carried
out,
but
P
antagonist
RU486
assess
activity.
Ovariectomy
increased
periodic
awakenings
compared
those
determined
SHAM
group.
very
effective
by
fifth
week
decreasing
arousal
achieving
similar
behavior
SHAM-control
Rats
well
planned
(0.66
mg/kg
4.4
mg/kg,
respectively).
lethal
events
occurred;
MTD
reached.
indicated
17β-E2
plus
assay
triggered
isotype
65
all
studied
incubation
medium
blocked
such
activity;
however,
action
67
RU486.
determined;
coincided
ET
PT
used.
However,
combination
restored
SHAMs
without
effects.
demonstrated
GAD65
tissues.
European Journal of Cancer,
Journal Year:
2022,
Volume and Issue:
175, P. 11 - 18
Published: Sept. 6, 2022
Despite
the
increased
number
of
novel
immunotherapy
(IO)
agents
under
current
development,
their
toxicity
profile
remains
to
be
fully
elucidated.An
IO
risk
stratification
model
was
developed
based
on
5
different
variables:
treatment-related
deaths;
rate
grade
≥3
adverse
events
or
treatment-emergent
events;
≥2
encephalopathy
central
nervous
system
toxicity;
cytokine
release
syndrome;
and
type
dose-limiting
toxicity.
Phase
1
trials
published
from
January
2014
December
2020
were
reviewed
categorised
our
into
three
categories:
low-,
intermediate-
high-risk.
Clinical
trial
variables
associated
with
high-risk
category.
To
review
quality
reporting
across
phase
trials,
a
subset
studies
further
examined
by
use
ASCO/SITC
Trial
Reporting
in
Immuno-Oncology
(TRIO)
standards.Different
compounds
demonstrated
diverse
profiles.
In
multivariable
analysis,
combination
versus
single
agent
treatment,
testing
anti-programmed
death-1/programmed
death
ligand-1
(anti-PD1/L1),
anti-cytotoxic
t-lymphocyte
antigen-4
(anti-CTLA4)
antibodies
anti-cancer
vaccines
higher
risk.
None
dataset
reported
all
items
included
TRIO
standards.Our
results
have
important
implications
for
future
clinical
design.
Additionally,
standards
are
urgently
needed.
DOAJ (DOAJ: Directory of Open Access Journals),
Journal Year:
2022,
Volume and Issue:
25(10), P. 730 - 734
Published: Oct. 20, 2022
Bayesian
statistics
is
an
approach
for
learning
from
evidences
as
it
accumulates,
combining
prior
distribution
with
current
information
on
a
quantity
of
interest,
in
which
posterior
and
inferences
are
being
updated
each
time
new
data
become
available
using
Bayes'
Theorem.
Though
frequentist
has
dominated
medical
studies,
been
more
widely
recognized
by
its
flexibility
efficiency.
Research
development
(R&D)
anti-cancer
drugs
have
so
hot
globally
recent
years
spite
relatively
high
failure
rate.
It
the
common
demand
pharmaceutical
enterprises
researchers
to
identify
optimal
dose,
regime
right
population
early-phase
R&D
stage
accurately
efficiently,
especially
when
following
three
major
changes
observed.
The
anticancer
transformed
chemical
biological
products,
monotherapy
combination
therapy,
study
design
also
gradually
changed
traditional
way
innovative
adaptive
mode.
This
raises
number
subsequent
challenges
decision-making
early
R&D,
such
inability
determine
MTD,
deal
delayed
toxicity,
response
dose-response
changing
relationships.
because
above
emerging
that
getting
attention
industry.
At
least,
decision-making,
could
potentially
help
achieve
higher
efficiency,
shorter
period
lower
investment.
expounds
application
drugs,
compares
analyzes
idea
scenarios
statistics,
aiming
provide
macroscopic
systematic
reference
all
related
stakeholders.
.【中文题目：贝叶斯方法在肿瘤新药早期临床研发中
的发展与应用】
【中文摘要：贝叶斯学派是通过综合未知参数的先验信息与样本信息，依据贝叶斯定理，求出后验分布，根据后验分布推断未知参数的统计方法。相比频率派，贝叶斯学派更加灵活、高效。肿瘤新药是全球研发的热点，但同时也存在高失败率的风险。在肿瘤新药早期研发中，高效寻找最佳剂量、优势人群、估计疗效和成功率是医药企业和研究者的共同需求。近年来，肿瘤新药研发呈现化学药物生物制品转变、单药治疗向联合治疗转变、传统设计向创新设计转变等新趋势；伴随出现的各种挑战，包括无法找到最高耐受剂量、延迟毒性、延迟反应、剂量疗效关系变化、剂量组合众多等。基于贝叶斯方法，恰当借用先验信息，能有效帮助企业在肿瘤早期研发中，实现从传统研发模式（高投入、长周期、低效率）向现代研发模式（低投入、短周期、高效率）的转变。研究还进行了贝叶斯方法在肿瘤新药早期研发的进展阐述，与频率派的理念、应用场景的比较分析，可为医药研发的所有从业人员提供宏观、系统的参考。
】
【中文关键词：早期试验；贝叶斯；
统计设计；肿瘤】.
