THIS WEEK
THIS WEEK
Articles appearing in this print journal have already been published
on thebmj.com, and the print version may have been shortened
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NEWS
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The trouble with dabigatran
Doctors and patients must
tread carefully through
emerging risks
Blake Charlton and Rita
Redberg
Assisted dying bill passes
second reading in Lords
Assess blood supply for vCJD
risk
She’s got a ticket to ride
Trusts say emergency
admissions will rise, but GPs
forecast a fall
Australia sees large
fall in smoking after plain
packs are introduced
New method of ovarian
stimulation is “promising” in
IVF, say scientists
Nurse refuses to partake in
feeding at Guantanamo
NICE sticks to its advice
to drop threshold for
prescribing statins
BMJ CONFIDENTIAL
Neil Bacon
is a kidney specialist turned
entrepreneur with two big
successes under his belt
26 July 2014
349:1-44 No 7968 | ISSN 1759-2151
LAUREN BURKE/PHOTOGRAPHER’S
CHOICE/GETTYIMAGES
EDITORIALS
Six AIDS experts are killed in
Ukraine air crash
Boehringer Ingelheim withheld
safety analyses on dabigatran
Fluid resuscitation
for people with
sepsis
Cholesterols:
good, bad, and
indifferent
Cardiovascular and
non-cardiovascular
effects of statins
UK legislation
targeting
“dangerous dogs”
Dabigatran:
The analyses
the regulators
didn’t see
EDITORIAL, p 7
FEATURE, p 15
DABIGATRAN
The analyses
the regulators
didn’t see
the bmj | 26 July 2014
ANALYSIS, p 21
• FEATURE, p 15
• ANALYSIS, p 21
8
Mass treatment with statins
True informed choice will require
wholesale changes to the way
we gather and communicate
evidence
Ben Goldacre and Liam Smeeth
• PRACTICE, p 38
9
Not so “good” cholesterol
But the HDL story isn’t over yet
Leonard Kritharides
• RESEARCH, p 11
10 Fluid resuscitation for people
with sepsis
It’s time to challenge our basic
assumptions
Simon G A Brown
• RESEARCH, p 12
p1
p30
p11
RESEARCH
11 Effect on cardiovascular risk
of the high density lipoprotein
targeted drug therapies niacin,
fibrates, and CETP inhibitors:
meta-analysis of randomised
controlled trials including
117 411 patients
Daniel Keene et al
• EDITORIAL, p 9
12 Randomised trials of human
albumin for adults with sepsis:
systematic review and metaanalysis with trial sequential
analysis of all-cause mortality
Amit Patel et al
• EDITORIAL, p 10
13 Subgroup analyses in
randomised controlled trials:
cohort study on trial protocols
and journal publications
The DISCO study group
14 Re-evaluation of link between
interpregnancy interval and
adverse birth outcomes:
retrospective cohort study
matching two intervals per
mother
Stephen J Ball et al
The BMA grants editorial freedom to the Editor of the BMJ. The views
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EDUCATION
STATE OF THE
ART REVIEW
30 Non-cardiovascular effects
associated with statins
Chintan S Desai et al
PRACTICE
GUIDELINES
38 Lipid modification and
cardiovascular risk assessment
for the primary and secondary
prevention of cardiovascular
disease: summary of updated
NICE guidance
Silvia Rabar et al
ENDGAMES
42 Quiz page for doctors
in training
MINERVA
44 The progression of rheumatoid
arthritis, and other stories
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THIS WEEK
BMJ CAREERS
p15
p27
p28
VIEWS
15 Dabigatran: how the drug
company withheld important
analyses
In an investigation by The BMJ
Deborah Cohen finds that
recommendations for use of
new generation oral anticoagulants
may be flawed because regulators
did not see evidence showing that
monitoring drug plasma levels
could improve safety
• EDITORIAL, p 7
• ANALYSIS, p 21
LETTERS
25 Harmful medical overuse
26 Complex regional pain
syndrome; Primary
healthcare and mortality; Mid
Staffordshire surgeon case
ANALYSIS
21 Dabigatran, bleeding, and
the regulators
Thomas J Moore and colleagues
highlight the differences in how
• EDITORIAL, p 7
• FEATURE, p 15
PERSONAL VIEW
27 Dog ownership has unknown
risks but health benefits
OBITUARIES
28 Ronald Arthur (Sam) Robinson
Psychiatrist who established
the world’s first comprehensive
psychogeriatric service
29 Paul Michael Anthony
Bowden; William Michael
Garraway; William Lloyd
Jones; Leela Menon;
Alexander Peter Beaton
Mitchell; Keith Rawlinson;
John Murray Miller Young
CAREERS
US and European regulators
managed the safety problems
of the new anticoagulant
dabigatran and ask both to think
again and mandate plasma
monitoring of dabigatran
FEATURES
• News: Distress
caused by GMC
treating health as a
conduct issue
• Trusts should learn
from John Lewis
• Simulation in
skills training
• Doctors as
chief executives
EDITOR’S CHOICE
The power to change
The politician’s favourite department
store has once again been held up as
an example of the way public sector
services should be run. Three years ago
the government announced plans for
parts of the public sector to adopt the
mutual status used by the John Lewis
Partnership, and councils and schools
have also considered restructuring
themselves along similar lines.
This week Matthew Limb looks at
the recommendations of a King’s Fund
report that calls for health service
staff to be given a stronger voice in
existing structures (p 3). “This might
include learning from the John Lewis
Partnership and other successful
mutuals on the mechanisms for
recruiting staff representatives and
Many in the NHS would
prefer it if greater credence
were given to staff
members’ ideas on how the
service should be run
supporting them in delivering their roles
effectively,” the report says.
The suggestion that ideas from retail
and other sectors can provide simple
solutions to the NHS’s problems is a
source of frequent annoyance to those
working in the health service. Many
in the NHS would prefer it if greater
credence were given to staff members’
ideas on how the service should be run.
Unfortunately too few current clinicians
are themselves willing to take on the
leadership and management roles that
hold the power to change many aspects
of the health service.
A panel discussion at last month’s
NHS Confederation conference in
Liverpool considered what doctors
could bring to senior management roles
in the NHS and what deters them from
taking on these roles (p 6). For some
doctors, frustration with the current
system will push them into pursuing
careers in senior management in the
NHS. But many others will need to be
persuaded that using their leadership,
analytical, and interpersonal skills to
improve health service management
could benefit patients as much as
providing care to individual patients.
Tom Moberly, editor, BMJ Careers
[email protected]
LAST WORDS
43 Is Coca-Cola’s antiobesity
scheme the real thing?
Margaret McCartney
Coming out of the box
Alison Cameron
Rachel Orritt
INSIDE • News: Distress caused by GMC treating health as a conduct
issue • Trusts should learn from John Lewis • Simulation in skills training
• Doctors as chief executives Followed by jobs and courses
careers.bmj.com | 26 July 2014
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THIS WEEK
26 July 2014 Vol 349
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PICTURE OF THE WEEK
A candlelight vigil held at the 20th International AIDS Conference in Melbourne this week. A tradition
at the AIDS conferences, ​the vigil ​​highlights ​the 35 million​lives lost due to HIV ​infection. ​T his year it
took on added meaning: six HIV researchers and lobbyists died on crashed flight MH17 en route to the
conference.
RESPONSE OF THE WEEK
MOST READ
I feel we have all eaten our way into this
diabesity epidemic and we must all take
every opportunity to help patients eat
their way out of it again.
Yudkin and Montori ask for a shift in
perspective—I suspect that it would
help if we as doctors prioritised working
on lifestyle changes with our patients
well before initiating drug therapy. The
diagnosis of pre-diabetes far from being a
threat can be a turning point and a golden
opportunity.
David J Unwin, GP partner/trainer,
Southport, UK, in response to, “The
epidemic of pre-diabetes: the medicine
and the politics”
(BMJ 2014;349:g4485)
Evidence based medicine: a movement in crisis?
Jeremy Hunt’s bizarre ideas show that he doesn’t understand
general practice
Evidence based medicine: a movement in crisis?
The epidemic of pre-diabetes: the medicine and the politics
Why the Assisted Dying Bill should become law in England
and Wales
THEBMJ.COM POLL
Last week’s poll asked:
Should doctors be required to record financial conflicts of
interest on the GMC register?
71%
voted yes (total 231 votes cast)
ЖЖBMJ 2014;349:g4601
This week’s poll asks:
Should all UK emergency departments include GP staff?
ЖЖBMJ 2014;349:g4654
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the bmj | 26 July 2014 THIS WEEK
EDITOR'S CHOICE
Faith, hype, and transparency
The histories of
dabigatran and
statins are tales
of incomplete
evidence, in which
people are being
expected to take too
much on trust
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This week we focus on two drug blockbusters at the heart
of one of the major issues The BMJ has campaigned on
in recent years: transparency, the focus of our Open Data
campaign. In the case of dabigatran and statins there
has been too much emphasis on faith and hype and not
enough on transparency. While The BMJ acknowledges
the drugs’ therapeutic value, the histories of dabigatran
and statins are tales of incomplete evidence, in which
people are being expected to take too much on trust.
Dabigatran was the first of the new oral anticoagulants
licensed to prevent stroke in patients with non-valvular
atrial fibrillation. It was approved by the US Food and Drug
Administration in 2010 and by the European Medicines
Agency for this use a year later. The drug’s unique selling
point, said its manufacturer, Boehringer Ingelheim,
was that it would need no monitoring, unlike warfarin.
Once on the market, dabigatran proved a rapid financial
success, but as sales soared concerns grew about the
reports of fatal bleeds that were beginning to emerge.
As Deborah Cohen reveals in The BMJ’s investigation
this week (p 15), the company withheld important
analyses from the regulators showing that monitoring
drug plasma concentrations and adjusting the dose
could improve safety. Instead, Boehringer Ingelheim’s
marketing strategy emphasised the no monitoring
message. “No need for regular blood tests to see if your
blood-thinning level is in the right range,” its advertising
boasted. Company documents revealed in the course
of US litigation over dabigatran show how, with proper
monitoring, and changing the dose, major bleeds could
be reduced by 30-40% in comparison with well controlled
warfarin. But, as Cohen discovered, neither doctors nor
regulators have ever been aware of these calculations.
Instead, guidelines (including those recently issued by
the UK National Institute for Health and Care Excellence
(BMJ 2014;348:g3655)) have recommended the new
generation of oral anticoagulants “in part because they
don’t require monitoring,” writes Cohen.
In an accompanying Analysis (p 21), Thomas Moore, of
the US Institute for Safe Medication Practices, says that
reducing bleeding “deserved to be ranked as a patient
safety issue of the first order.” One problem, as Rita
Redberg and Blake Charlton point out in their editorial
(p 7), is that dabigatran benefited from FDA programmes
to stimulate innovation, “which also contributed to a less
robust evaluation of risks and benefits.”
Statins, as Ben Goldacre and Liam Smeeth write in
their editorial (p 8) to accompany our summary this week
of NICE’s updated guidance on statins for prevention of
cardiovascular disease (p 38), are more likely to do good
than harm. And yet, they add, “Important questions on
comparative efficacy, and efficacy in different risk strata,
have never been adequately answered.” What is needed
for informed choice when offering a preventive drug to
potentially large numbers of healthy people, Goldacre
and Smeeth say, is better data, from bigger trials,
and better risk communication than for conventional
treatment. They conclude, “Without such innovation
in the use of medical data, we can say only that statins
are—broadly speaking—likely to do more good than
harm. That is not good enough.”
Trevor Jackson, deputy editor, The BMJ
[email protected]
Cite this as: BMJ 2014;349:g4793
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the bmj | 26 July 2014