Transcript Why I published “the albumin paper”: confession of a buccaneering editor Richard Smith

Why I published “the
albumin paper”: confession
of a buccaneering editor
Richard Smith
Editor, BMJ
October 2001
Hypothesis One
• Editors are shadowy, wayward pictures
who prefer the dark to the light and are
happiest consorting with “les belle de
nuits”
• They love sensation, any sensation
• Nothing gives them more pleasure than
to upset solid, upstanding people like
intensivists
• The “albumin paper” provided a
momentary fix to feed these dubious
pleasures
Hypothesis two
• The paper asked an important question
• The methods were “good enough”
• ASIDE: the invention of the “good
enough mother” may be one of the
greatest inventions of the 20th century;
concepts of the “good enough editor” or
“good enough intensivist” follow
• The paper was suitably tentative, even if
some of the subsequent comments were
not
What I want to talk about
• The new world of evidence
based practice
• My version of the albumin
story
• Intensive care in an evidence
based world
Is evidence based practice
a radical change?
• Combines with other drivers of
change
• “Consumerism”; the resourceful patient
• The arrival of the internet
• The desire of owners to manage more the
clinical process
• Growing gap between what could be done
and what can be afforded
Has EBP changed the world?
• Source of
knowledge is
expert opinion
• Source of knowledge
is systematic review
of evidence
• Clinical skills are • Clinical skills can be
audited and managed
seen as
semimystical
• Research is
marginal to
practice
• Research and
evidence go together
Has EBP changed the
world?
• Analysis of
research is
haphazard
• Analysis of
research is
systematic
• Not important to
gather new
evidence from
patients
routinely
• Patients should
be included in
trials wherever
possible
Has EBP changed the
world?
• Only lip service
is paid to
keeping up to
date and
learning new
skills
• Most medical
care is assumed
to be beneficial
• Essential to keep
learning new
skills
• Widespread
recognition that
the balance
between doing
good and harm is
fine
Has EBP changed the
world?
• Clinical
performance is
not
systematically
audited
• Clinical
performance is
regularly
reviewed and
managed
• Managers have
little
involvement in
clinical proceses
• Managers are
involved in
clinical
processes
Has EBP changed the
world?
• Organisational
model is
hierarchical
• Doctor patient
relationship is
essentially
master/pupil
• Organisational
model is much more
democratic, based
on ability to use
evidence
• Patient partnership
is the norm
Has EBP changed the
world?
• Patients do not
have easy
access to the
knowledge base
of doctors
• The doctor is
smartest
• Patients have as
much access to
the evidence
base of
medicine as
doctors
• Often the patient
is smarter
The albumin story: my view
• Albumin has been used for 50 years
to treat the critically ill
• The “theory” behind the treatment
was based on hypoalbuminaemia
being associated with higher
mortality (undoubtedly true),
oedema, and “low serum oncotic
pressure”
The albumin story: my view
• The theory was: “X being low is
bad: giving X will be good”: Is this
simpleminded?
• Like surgical “theory”: something
in the body is bad: if we cut it out
things will be better: result radical
mastectomy; hemicorporectomy
The albumin story: my view
• “Respectable” intensivists had
doubts about the effectiveness of
albumin
• “Currently, the widespread use of
albumin has more to do with word
association and the treatment of
items that are marked on a pathology
form with an asterisk than with
scientific medical management.” Neil
Soni, BMJ, 1995
The albumin story: my view
• There was big worldwide variation in
the use of albumin: generally,
Commonwealth countries used it a
lot; Americans used it much less
• The story is complicated (as always)
by commercial factors: albumin is
expensive, and many peoples’ jobs
depend on it
The albumin story: my view
• Enter some honest
Cochraneites/EBMers
with no particular axe to
grind, no money to make,
no reputation to lose
The albumin story: my view
• Experience--especially
experimentally collected data-trumps theory
• The thinking behind the renaissance:
surely intensivists are not
medievalists
• Surely intensivists don’t want to be
associated with the chicanery of
management consultancy: “It
may(not) work in practice, but will it
(not) work in theory?”
The albumin story: my view
• The Cochraneites follow their usual
method
• They pose a question, systematically
search for all relevant studies, set some
quality criteria, perhaps combine the data
statistically, and see what the data say
• A crucial observation is that the data are
poor: the big, randomised, double blind
study that should have been done has not
been done
The albumin story: my view
• The data suggested--to their surprise
but fairly consistently--that albumin
kills more people than it saves
• They write up the study with a
suitably tentative conclusion
The albumin story: my view
• “There is no evidence that albumin
administration reduces mortality in
critically ill patients with hypovolaemia,
burns, or hypoalbuminaemia and a strong
suggestion that it may increase mortality.
These data suggest that use of human
albumin in critically ill patients should be
urgently reviewed and that it should not be
used outside the context of rigorously
conducted randomised controlled trials.”
The albumin story: my view
• The study is submitted to the BMJ
• We decline to fast track the study
• The peer review of the study is even more
extensive than usual, generating pages of
comments and revisions
• The clinical reviewer is against publication-partly because of unhappiness with the
whole methodology (“garbage in, garbage
out”--but this is all the evidence we have)
An aside: problems with peer review
•
•
•
•
•
•
•
•
•
No evidence of effectiveness
“Ineffective”: doesn’t detect errors
A lottery
A black box
Slow
Expensive
Biased
Easily abused
Can’t detect fraud
An aside on peer review
• “The benefit of peer review
probably comes not from
sorting out what to reject and
what to publish but rather
from improving what is
eventually published.”
Who makes the final
decision at the BMJ?
• Two practising doctors (mostly
physicians) with extensive
experience of peer review
• One or possibly two editors
• A statistician
• Everybody reads every word
• A majority vote carries the day
• The buck stops with the editor (me)
The albumin story: my view
• A heavily revised paper is published
• An editorial written by an intensivist is
generally supportive
• A scientific commentary provides
modern pathophysiological explanations
of why albumin might make things
worse rather than better
• A TWIB overdoes it: “Albumin
administration increases mortality in
critically ill patients”
All hell
breaks
loose
The albumin story: my view
• 30 rapid responses
• “For the Editorial Board of the BMJ
to sanction a headline-grabbing
press release on this paper is
nothing short of scaremongering,
and further justifies my decision
three years ago to resign my
membership of the BMA.”
• Keith Judkins, intensivist
The albumin story: my view
• A reasonable test is to ask what I would
want for myself, as a patient, or for
someone I cared for. In brief, I would
attempt to sue anyone who gave me an
albumin infusion. And, as for any attempt
to secure my informed consent to take
part in a randomised trial (or my assent on
behalf of someone I cared for who was
unable to give informed consent) - forget
it!
• [Sir, wow] Iain Chalmers, head of the UK
Cochrane Centre
The aftermath
• A moderate editorial argues that
“rather than fulminating we seek to
answer the questions raised”
• FDA advises that the results deserve
serious attention
• A trial is proposed
• Use of albumin drops
The aftermath
• Authors and editor get gently roasted at
British intensive care meeting
• Intensivists seem to argue that “A
question like whether albumen works is
not useful. What matters is the whether
the individual intensivist can
compensate for the individual patient’s
seriously dreranged physiology”
• Editor says this is exactly the argument
used by psychoanalysts
Two years
On all is
sweetness
And light
Intensivists and evidence
• Albumen
• Low dose dopamine to prevent
renal failure
• Pulmonary artery catheters
• Ranitidine to prevent GI bleeding
• Various antesepsis regimens
Why the problem?
• RCTs are especially hard to do in
intensive care: urgency, very sick
patients, multiple pathology, each
patient is unique, consent
• It must be hard to do nothing
• “Good surgeons know how to operate.
Better surgeons know when to operate.
The best surgeons know when not to
operate.” True as well for intensivists?
Conclusion
• The “albumen story” has posed
important questions that are now
being answered
• It’s prompted understanding (and
misunderstanding--they always
go together) of EBM among
intensivists
• We all got a little carried away
• Cue music: Je ne regret rien