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Papers
Paul Glare, Kiran Virik, Mark Jones, Malcolm
Nicholas Christakis
tified by a systematic
To
Objective
review
systematically
physicians' clinical predictions of survival in
terminally
sources
Data
ill cancer
Medline
Library,
We searched Ovid Premedline
(1996-2000), Embase, Current Contents, and
as hand
as well
databases
Cancerlit
searching.
Study selection Studies were included if a physician's
temporal clinical prediction of survival (CPS) and the
actual survival (AS) for terminally ill cancer patients
were available for statistical analysis. Study quality was
assessed by using a critical appraisal tool produced by
the local health authority.
synthesis
with
the
data
and
other
regression
inclusion
and
pooled
multivariate
and
criteria,
8 were
techniques.
?valuable,
cases
of
and
providing
survival
overestimated
at least
by
four weeks in 27%. The longer the CPS the greater
the variability inAS. Although agreement between
CPS and AS was poor (weighted k 0.36), the two were
highly significantly associated after log transformation
rank
(Spearman
Consideration
use
correlation
of
improved
the additional
although
of
Heterogeneity
comprehensive
overestimate
survival,
correlated
with
their
a
are
predictions
the
survival;
of
itmay
affect
good
death.
patients'
Accurate
clinical
incorporating
are needed.
results
given
date
days
patients
of death
were
not
retrievable
the
contacted
studies,
however,
curate
and
survival
of
Do
vival
of
reliable
estimates
have
overly
sion
patients
doctors
overestimate
ill cancer
terminally
are doctors
of
in
survival
patient
26 JULY 2003
are
inac
the
when
predicting
cancer.24
or underestimate
patients
the
sur
on
How
average?
survival? Do doctors'
information
provide
or risk factor models
beyond
prognostic
We
obtained
individual
BMJ VOLUME 327
for
question
Several
illnesses.1
that doctors
estimating
then
review
retrievable
from
the authors.
re-read
and
studies
from
selected
for
the
inclu
them
evaluated
independently
for their quality by using the Method for Evaluating
Research and Guideline Evidence (MERGE) guide for
critical
coding
appraisal.5
for
system
MERGE
incorporates
the quality
appraising
a four
of a study
point
and
scoring the risk of bias from "A" (low) through "Bl"
and "B2" to "C" (high).
The individual patient data for CPS and AS could
be abstracted directly from papers
if they were
characteristics
Study
The
electronic
search
prognostication
of survival
incurable
suggested
neither
obtainable
of us
in the
we
publication
directly
to obtain
them. We
excluded
Results
for
is a central
optimistic
with
terminal
of how
the
explanation
If the raw data for clini
the
were
data
nor
publication
Three
from
authors
if these
papers
of
papers
Data
far advanced,
an
provided
was determined.
to overestimate
prospects
prediction
doctor?"
prediction,
for each
cal prediction of survival (CPS) and actual survival (AS)
six
I have,
strategy.
survival
temporal
made
prospectively
or weeks,
section
papers,
inclusion
do
search
2001.
cancer
terminal
Introduction
long
with
the
11 other
data from
bmj.com
above
and
for outcome?
studies
iden
available
entered
we
22 citations,
produced
The
relevance.
hand
apparent
studies. After
excluded
five
that
not
yielding
search
these
reading
did
the
criteria.
on
1594 patients
(80.3% of
for
from
of
analysis
eight
these
into the
meta-analysis.2
the
total) were
studies,
3 6 7_1?n
and we
Because
some individual CPS or AS data were missing,
complete
17
meet
CPS-AS
dyads
were
available
for
analysis.
1563
We
extracted individual patient data from tables or figures
910 n
of
four
studies
and
(n=296),2
the
authors
generously provided us with their original data for the
other four (n=1280). Four studies were from the
United
one
was
involved
910 u
Kingdom,2
from
the United
referring
three
States
doctors,710
were
from
Italy,6"8 and
studies
(table
l).3 Two
and
the rest
involved
195
This content downloaded from 130.132.173.137 on Tue, 24 Mar 2015 16:56:41 UTC
All use subject to JSTOR Terms and Conditions
Department of
Palliative Care,
Royal Prince Alfred
Hospital,
Camperdown, NSW
2050, Australia
Paul Glare
head of department
Kiran Virik
researchfellow
Cochrane
January
a
included
section
in
identified
"How
of
for details
bmj.com
Contents,
on
19
databases
as a table or scatter
and AS
CPS
presented
plot. When
were
we
in summarised
form
the
presented
sought
individual
data from
the authors.
patient
highly
have
predictions
are miscalibrated.
even
if
they
with
patients
their tendency
ability
for
caring
to be aware
as
clinicians consistently
actual
discriminatory
Clinicians
achieving
models
a
precluded
meta-analysis.
Although
survival,
results
studies'
the
Conclusions
need
0.001).
and
status, symptoms,
performance
the accuracy
of the CPS,
value was
small.
steroids
of
P<
0.60,
Cancerlit
We obtained potential papers to see if theymet the
following preset selection criteria: (a) the study
involved patients with far advanced cancer; (b) the
methods
1563 individual prediction-survival dyads. CPS was
generally overoptimistic (median CPS 42 days,
median AS 29 days); itwas correct to within one week
in 25%
See
(Jan 2001) and Medline
Current
Embase,
(1966-2000),
and
Library,
patient by a doctor; (c) the results section provided the
patients' individual survival durations; and (d) the
analysed
studies were identified; 12met
17 published
Results
were
Raw
questions.
Methods
patients.
Cochrane
these
a
strategy and did
search
to answer
meta-analysis
of
the accuracy
777/s is an abridged
version; the full
version is on
Simes,
John
bmj.com
Abstract
Data
Steffen Eychmuller,
Hudson,
in
survival predictions
A systematic review of physicians'
terminally ill cancer patients
NHMRC Clinical
Trials Centre,
University of
Sydney, Sydney,
Australia
Mark Jones
biostatistician
John Simes
director
Department of
Statistics, Macquarie
University, Sydney
Malcolm Hudson
professor
Department of
Palliative Care,
Kantonsspital,
St Gallen,
Switzerland
Steffen Eychmuller
medical director
Department of
Health Care Policy,
Harvard Medical
School, Boston, MA,
USA
Nicholas
Christakis
professor
Correspondence
P Glare
[email protected].
gov.au
BMJ 2003;327:195-8
to:
Papers
Table 1 Summaryof the eight studies includedin the systematic review
No of
sites/doctors
Quality
Study
rating*
(3) Heyse-Moore,198716
Maltoni,
(4)
(5) Maltoni,
Individual
Median (IQR)CPS
(days)
patient data
71
1/? Parkes,19723
C
(1)
28(24-56)
(2) Evans,
198515_C_1/6_42_81
(28-182)_120(43-180)_069_0.40
C_1/?_50_56
(33-84)_14
(7-28)_026_0.06
199413_B1_1/4_100_42
(28-56)_32
(13-63)_O60_0.34
19958_B1_22/?_530_42
Oxenham,
(6)199821_C_1/5_21_21
(7) Maltoni,
199914_B1_14/?_451f_42
(8) Christakis,
Median (IQR)AS
Rank
k
correlation
(days)
Weighted
0.31
21(9-34) 0.49
20004_B1_5/343_326_77
(28-70)_32
(13-62)_O70_0.44
(14-35)_15
(9-25)_073_0.52
(21-70)_33
(14-62)_O70_0.44
(28-133)_24
(12-58)_O50_0.25
(28-84)_29
(13-62)_O60_0.36
Overall_?_?_1591_42
AS=actual survival; CPS=clinical prediction of survival; IQR=interquartilerange; ?=number of clinicians making predictions either not published or not known.
*According to MERGEdocument: B1=low-moderate risk of bias; C=high risk of bias.6
flncluded 36 patients who were censored (that is, still alive).
care
specialists).
n
and
hospital,21()
All
cared
for at home.
Three
doctors
(palliative
"receiving"
in
involved
studies
patients
involved
patients
involved
patient
for
being
the primary
data
Quantitative
that were
populations
cancer
site.
the
0.51
studies
heterogeneous
synthesis
as
assessed
involvement
and
prediction,
care
in
providing
ongoing
use,
the
of
to the
one
to within
to within
two weeks
in 25%
week
in 43%,
correct
and
correct
of cases,
to within
four
in 61%. CPS overestimated AS by at least four
weeks
in 27%
of cases
and
it by at least
underestimated
in 12% of cases. Although
between
agreement
CPS
and
the level of
was
AS
only
fair
(weighted k 0.36), the log transformation of CPS was
significantly
AS
(Spearman
correlated
with
the
transformation
log
2,
correlation
rank
0.60,
the models
Karnofsky
described
three
into
status
performance
above
subgroups
scores:
<40
with
the
based
on
(n=330),
40-50
(n=457), and >60 (n=194). For each model,
log(CPS) explains more of the variation in log(AS) as
the patient becomes sicker (table 2). The additional
provided
the
by
dyspnoea,
of how poor
other
steroid
the
factors
prognostic
use)
patient's
changes
performance
little,
is.
Discussion
Statement
of principal
findings
ill cancer
(a
terminally
patients
a median
to death with
survival
very close
population
were
of
four weeks)
inaccurate.
Doctors
approximately
in
overestimated
the duration
of survival
consistently
seven
of the
studies.
inaccurate,
Despite
being
eight
are
clinical
clinical
useful;
predic
predictions
clinically
Doctors'
predictions
for
tion of survival (CPS) and actual survival (AS) were
Study 2
in study 2 survived much
in the other
shortest
seven
consistendy
in the median
and
studies
of heterogeneity,
studies
for extensive
limited
With
difference
Because
between
of
3 and
6
of
study
of
lack
AS
and
indica
strong
the data of the
combining
eight
was not
statistical
appro
analysis
a
the aim of
doing
comprehensive
(figure).
tion
which
studies,
longer than the
the exception
A
overestimated
AS.
survivals.
uniformity
CPS
is apparent
priate,
dyspnoea,
?154()=32.3,
aggregation
CPS
factors.
prognostic
found
that palliative
and
all
log(KPS)
we
Study 1
The patients
patients
the
had
based
of
P< 0.001).
Statistical
anorexia,
repeated
divided
(anorexia,
weeks
four weeks
15 patient
elimination
results
summary
correct
on
patients
value
predicting
patient.
When all 1563 ?valuable CPS-AS dyads were pooled,
the median CPS was 42 days and the median AS was
29 days (table 1), a difference of 13 days. Overall, CPS
was
in
the variation
of
0.54).
irrespective
Simple
50%
Prediction ofAS according to health status
to recruitment,
in
the
in relation
variations
prediction
clinical
of the doctor
the predic
experience
making
to other
clinical
when
information
tion, access
making
the
based
backwards
We
biases included the timing of
cohort Misclassification
than
biased
being
with half
biases
and misclassification
(selection
biases),
a narrow
at a
biases
included
risk. Selection
being
high
to use an
failure
of patients
and
spectrum
inception
doctor
a model
Using
steroid
square
were
studies
that greater
contributed additional value to log(CPS) when predict
ing log(AS), but the additional value was small (R
assessment
Validity
All
eight
indicates
log(AS) was explained by log(CPS). Next, we generated
rest
the
Study 3
Study 4
Study 5
Study 6
Study 7
Study 8
-20-40
Clinician underpredicts
meta-analysis.
0
60
20
40
Clinician
overpredicts
Difference (days)
Modelling CPS and otherprognostic factors
In the subset of 981 patients with data for multiple
prognostic
cantly
variables,
correlated
with
log(CPS)
log(AS).
was
The
statistically
R square
signifi
of
value
Difference between actual survival and clinical prediction of survival
for terminally ill cancer patients (median and 95% confidence
interval)
196 BMJ VOLUME 327
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All use subject to JSTOR Terms and Conditions
26 JULY 2003
bmj.com
Papers
correlated.
strongly
of
modelling
Italian
seems
CPS
to be
variables
These
patients
factors
to a limited
and
Strengths
in
and
in
the
than
used
status
performance
more
accurate
status.
better
factors
prediction
data
supplementary
in
included
studies
our
Furthermore,
from
review
independent
two
large
indicated
that
conventional
this
population,
as
CPS was
although
worse
performance
to refine
the clinician's
weaknesses:
systematic
answers
numerical
providing
as well as
its clinical
usefulness
on
this
of the best
to better
and
stand
Our
electronic
one
Only
electronically.
For
appraising
issues
over-riding
to use,
criteria
the
quality
The
first
arose.
and
the
with
diagnostic
other
unlike
with
exists
test
which
outcome
bias
itself.
evaluations,
can be
CPS
This
but
irrelevant,
quality
form
of
criteria
it reduces
when
a
defined
other
studies
predicts
the
than
verification
a
a
future
concerns.
important
validity
and train
experience,
specialty,
of the clinician
the
also be
may
ing
making
predictions
to be
relevant
and
needs
available.
As
associated
to
follow
up
about
Information
decisions
about
the
the
treatments
sustaining
also
affect
or
application
withholding
or antibiotics
such as fluids
or
the
survival,
physician
not
should
the
prediction
making
care. These
the patient's
clinical
lems with
the
the
absence
not
may
be
The
will
investigator
be
our
criteria,
of
comprehensive
quality
ratings
the
studies
prevented
However,
meta-analysis.
us from
some
pooling of the data was still possible and we believe our
principal
are valid.
findings
Implications
or how
The key issue with CPS
whether
is not so much
to
it is
rather
improve
physicians'
discriminatory
ability;
or
to
how
them
in their formula
support
supplement
to enhance
tion of
in
how
and,
prognosis
particular,
to be aware of their ten
their calibration.
Doctors
need
dency
are
who
to
serious
overestimate
approaching
implications
inappropriate
treatment
and
tive
care.
train
are
or
training,
whether
on
be used
methods
used
for
a
doctor-patient
made
predictions
at
of
the
and
ones;
as the reference
for
this
demo
makes
the doctor
initial
The
BMJ VOLUME
prognosis
death.
This
for
the
in
cancer
optimism
patient
patients
have
may
terms
in
of
disease
of
application
controlling
or
to a
in referral
delays
hospice
pallia
results
that
of the meta-analysis
suggest
327
26 JULY 2003
bmj.com
or
to
ways
the basis of our findings, CPS
the CPS. On
now
the
of
whether
to
superior
studies
predictions
not
warranted.
whether
experience
the nature
is important;
are
predicting
standard
for evalu
survival,
and
it has
how doc
Understanding
that
and interventions
predictions,
to make
better
doctors
predictions
purpose.12
their
formulate
are
than
factor"
inexperienced
also worthy
of consideration.
are
better
to
able
death,
anticipate
they
will be likely to be better able tomake judicious use of
treatments
medical
and
unnecessary
avoiding
the use of palliative
optimise
near
treatments
the end of
to achieve a good
life. They will also help patients
if for no
death
fil
to ful
they help
the
of
about
kind
expectations
want.
not all
want
they
patients
Although
information
all of the time, most
prognostic
want
most
most
the
of
the
information
of
the
patients
time.3 Doctors
near
the
that
than
own
patients'
information
all
reason
other
end
two
face
life:
of
in
prognosticating
accurate
predictions
challenges
formulating
What is already known on this topic
Accurate
of the timing of death
prediction
for good
clinical decision
important
making
care of
with a terminal
illness
patients
Doctors'
and
often
are not
predictions
overestimate
survival
survival
is
in the
accurate
very
valid.
heterogeneity
a
doing
life
of
for
responsible
are the
types of prob
in the review, and, in
the studies
of
quality
of established
tors
of
accuracy
is needed
other
could
ating
been
the
miscalibration
research
enhance
care,
of applying
of CPS. As
for
the
If doctors
standard
to
in its evalua
screening
to be a well
needs
population
and
bias and
loss
spectrum
cohort,
are
inception
compared,
Further
However,
prognosis.
reference
no
is similar
the study
Therefore,
of
appraising
test, CPS
to
how
survival has to do
and
blinding
the usefulness
makes
diagnostic
state and so
health
tion.
than
0.27
is typically 30% shorter
at
look
relationship
follow
up
the accuracy
of CPS
the evaluation
of a
to
in concept
to studies
closer
test
that merely
document
what
deciding
deciding
predicting
to compare
studies
prognosis,
are
AS
0.50
0.38
and future
research
questions
seems
to be related
to AS, further
CPS
difference;
two
studies
the
was
was
second
apply them. Although
with
of
Because
graphics,
its limitations.
lacked
strategy
sensitivity.
was
studies
relevant
located
three
Unanswered
under
search
in
0.15
0.08
0.25
CPS=clinical prediction of survival; KPS=Kamofsky performance status score.
of survival
is correlated
with AS.4 Our
and
predictors
on
review
extends
those
conclusions
by
focusing
to the characteristics
several
of the
questions
relating
CPS
Other prognostic factors alone
40-50_KPS
0.24
a "correction
but
predicted,
arbitrarily
assigning
cannot
be recommended.
of 0.7 to their CPS
review
is one
available
Model_KPS
<40_KPS
0.35
CPS alone0.46
survival of patients
that CPS
were
variables
prognostic
CPS and other prognostic factors
with
comparison
studies
previous
One
previous
qualitative
data on multiple
for whom
patients
symptoms,
with
may
help
extent.
topic also concluded
prognostic
such
Table 2 R square values obtained for threemultiple linearregressionmodels in981
inaccurate,
Though
with
survival
doctors'
correlate
predictions
What this study adds
Doctors'
accurate
survival
closer
predictions
to the date
become
more
of death
of up to six
inaccurate,
predictions
as they
in length are nevertheless
reliable,
are
correlated
with actual
survival
highly
Though
months
Traditional
prognostic
status,
performance
add litde information
physician's
indicators
anorexia,
such
as
and breathlessness
to that contained
in the
prediction
197
This content downloaded from 130.132.173.137 on Tue, 24 Mar 2015 16:56:41 UTC
All use subject to JSTOR Terms and Conditions
>60
Papers
and
been
them.
communicating
the subject
ter, but we
believe
to achieve
a
of
The
former
act, which
is a predicate
are
necessary
this review,
that both
for
for
has
the
lat
patients
death.
good
See bmj.com
Contributors:
None.
Funding:
interests: None declared.
Competing
Ethical approval: Not needed.
1
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consent
Novel
ELPS
to
unable
77ms is an abridged
version; the full
version is on
Elizabeth
5
Liddel J,Williamson M, Irwig L.Method for evaluating researchand guideline
evidence. Sydney: NSW Health Department,
1996. Available at
mternal.healm.nsw.gov.au/public-healtli/crcp/publications/general/
mergetotpdf
6 Maltoni M, Pirovano M, Scarpi E,Marinan M, Indelli M, Arnolodi E, et al.
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physicians' survival predictions for terminally ill cancer patients using the
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(Accepted 12June 2003)
for research
process
in dying patients
consent
give
Rees, Janet Hardy
bmj.com
Department of
Palliative Medicine,
Royal Marsden
Abstract
terminal
Correspondence
J Hardy
drugs
and glycopyrronium
noisy
("death
BMJ 2003;327:198-200
rattle").
Palliative
acceptability
cancer
major
to a
palliative
the consent
nervous
central
causing
been
the
cally
drug
is a quaternary
bromide
care
blood-brain
accrual;
relative
process.
to
consent
advance
gave
to date, 58
in the
participate
study.Of these, 15 patients developed death rattle and
were
to receive
randomised
died
patients
randomised;
Conclusions
on
either
or
hyoscine
the
care wards
palliative
but were
not
12 patients are still alive.
Initial assessment suggests that this is a
to be
research
process
allowing
are unable
to
in
who
undertaken
give
patients
consent
at the time of randomisation.
accrual
Patient
workable
rates
consent
to date
adequate
research
are
lower
was
allotted
to answer
the
question.
consent
of
After
consent
of
no
who
established
In order
receive,
advance
necessary
to
and
means
lawyers,
the
that
us
advised
was
the
process
consent
in this situa
consent
means
of obtaining
only possible
a method
details
tion. This paper
consent
the
interim
and
results
advance
of obtaining
of the recruitment
process.
All
participate
comprehend,
to allow
a
would
legal
ethicists
care wards
to the
admitted
patients
palliative
are
Marsden
Hospital
given
an
Royal
is
a
situations.
with
an
of
needed
patients
at the time of randomisation.
committee
ethics
development
from
in such
consultation
local
this, we
do
the
in the
glycopyrronium
context
within
the
Methods
Introduction
The patient
information sheet
on bmj.com
the
assess
to
study
and
trial. To
controlled
to obtain
a
to undertake
obtaining
to
consent
give
the United
Kingdom
our
histori
to recruit
than needed
in the time
numbers
aim
be unable
exist
has
effects,
Glycopyrronium
that does not cross
amine
of hyoscine
efficacy
of
death
rattle
control
means
side
system
of
choice.
barrier.
randomised
In
16 patients died elsewhere; 15
glycopyrronium;
their
in
large airways,
resulting
noisy
breathing
as "death rattle." This
can be distress
described
usually
to relatives
and
for
ing
people
caring
patients.
dying
are
Two
antimuscarinic
for the
used
drugs
commonly
a
of this condition.
control
Hyoscine
hydrobromide,
amine
that can cross
the blood-brain
barrier
tertiary
Our
Patient
Results Of the 107 patients approached
patients
of
secretions
"death rattle" and thus be
for randomisation.
eligible
measures
outcome
Main
of
in a
admitted
ward who may develop
retained
can
for that trial.1
consent
protect
Only
fully informed
consent
such
is often
patients'
autonomy.2
Obtaining
in some
such as emergency
very difficult
disciplines,
care.35
care, and palliative
medicine,
elderly
are often
to clear
unable
secretions
patients
Dying
from
hydrobromide
in themanagement
with
care wards
Patients
Participants
(hyoscine
bromide)
associated
respirations
Setting
centre.
in the
patients
an advance
consent
study of
a randomised
controlled
trial of
to
process
support
two antimuscarinic
to:
in
phase.
Feasibility
Design
Janet Hardy
consultant in
palliative care
consent
of advance
process
develop
to be undertaken
research
Objectives
to enable
Hospital, Sutton,
Surrey SM2 5PT
Elizabeth Rees
research nurse in
palliative care
a
To
in a clinical
and
them
to
retain
give
all
fully
must
trial patients
the information
informed
consent
sheet explaining
research
studies
ability" of
in the
information
about
that theymight be approached
during
patients
their
admission.
is determined
198 BMJ VOLUME
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327
The
"trial
suit
at pre-round
26 JULY 2003
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