bmj open · conclusions: ct scanning for all anticoagulated patients with head injury is not...
TRANSCRIPT
For peer review only
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling of an observational
cohort
Journal: BMJ Open
Manuscript ID bmjopen-2016-013742
Article Type: Research
Date Submitted by the Author: 03-Aug-2016
Complete List of Authors: Kuczawski, Maxine; University of Sheffield School of Health and Related Research, School of Health and Health Related Research Stevenson, Matt; University of Sheffield School of Health and Related
Research, School of Health and Health Related Research Goodacre, Steve; University of Sheffield, Medical Care Research Unit Teare, M; University of Sheffield, School of Health and Related Research Ramlakhan, Shammi; Northern General Hospital, Emergency Department Morris, Francis; Northern General Hospital, Emergency Department mason, suzanne; university of sheffield, UK, school of health and related research
<b>Primary Subject Heading</b>:
Emergency medicine
Secondary Subject Heading: Health economics, Health policy, Radiology and imaging, Neurology
Keywords: Anticoagulation < HAEMATOLOGY, Head & neck imaging < RADIOLOGY & IMAGING, TRAUMA MANAGEMENT, Warfarin
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open on O
ctober 18, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2016-013742 on 13 Decem
ber 2016. Dow
nloaded from
For peer review only
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling
of an observational cohort
Maxine Kuczawski, Matt Stevenson, Steve Goodacre, M Dawn Teare, Shammi Ramlakhan, Francis
Morris, Suzanne Mason
Maxine Kuczawski, School of Health and Related Research, University of Sheffield, Sheffield UK
Professor Matt Stevenson, School of Health and Related Research, University of Sheffield, Sheffield
UK
Professor Steve Goodacre, School of Health and Related Research, University of Sheffield, Sheffield
UK
MD Teare, School of Health and Related Research, University of Sheffield, Sheffield UK
Dr Shammi Ramlakhan, Emergency Department, Northern General Hospital, Sheffield UK
Dr Francis Morris, Emergency Department, Northern General Hospital, Sheffield UK
Professor Suzanne Mason, School of Health and Related Research, University of Sheffield, Sheffield
UK
Corresponding author: Professor Suzanne Mason
School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street,
Sheffield S1 4DA; [email protected]; 0114 222 0694
Word count: 2680 (excluding title page, abstract, references, tables and figures)
Page 1 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
ABSTRACT
Objectives: It is not currently clear whether all anticoagulated patients with a head injury should
receive CT scanning or only those with evidence of traumatic brain injury (e.g. loss of consciousness
or amnesia). We aimed to determine the cost-effectiveness of CT for all compared to selective CT
use for anticoagulated patients with a head injury.
Design: Decision-analysis modelling of data from a multi-centre observational study.
Setting: 33 Emergency Departments in England and Scotland.
Participants: 3566 adults (aged ≥16 years) who had suffered blunt head injury, were taking warfarin
and underwent selective CT scanning.
Main outcome measures: Estimated expected benefits in terms of quality-adjusted life years
(QALYs) were the entire cohort to receive a CT scan; estimated increased costs of CT and also the
potential cost implications associated with patient survival and improved health. These values were
used to estimate the cost per QALY of implementing a strategy of CT for all patients compared to
observed practice based on guidelines recommending selective CT use.
Results: Of the 1420/3534 patients (40%) who did not receive a CT scan, 7 (0.5%) suffered a
potentially avoidable head injury related adverse outcome. If CT scanning had been performed in all
patients, appropriate treatment could have gained 3.41 additional quality-adjusted life years (QALYs)
but would have incurred £193,149 additional treatment costs and £130,683 additional CT costs. The
incremental cost-effectiveness ratio of £94,895/QALY gained for unselective compared to selective
CT use is markedly above the threshold of £20-30,000/QALY used by the UK National Institute for
Care Excellence to determine cost-effectiveness.
Conclusions: CT scanning for all anticoagulated patients with head injury is not cost-effective
compared with selective use of CT scanning based on guidelines recommending scanning only for
those with evidence of traumatic brain injury.
Page 2 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Trial registration ClinicalTrials.gov NCT 02461498.
ARTICLE SUMMARY
Strengths and limitations of this study
• This is the largest study to model options for the clinical management of anticoagulated
patients taking warfarin with a head injury.
• The methods used to estimate health gain from treating additional cases detected by
universal CT scanning are transparent and reproducible, and were robust to the sensitivity
analyses undertaken.
• Some patients who suffered adverse outcome may not have been identified on follow-up
potentially being a limitation of the study, leading to underestimation of the potential
benefit of CT scan for all patients.
Page 3 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
BACKGROUND
It is estimated that at least 1% of the United Kingdom (UK) population are taking an anticoagulant,
such as warfarin, increasing to 8% in those aged 80 years and over[1, 2]. People taking an
anticoagulant who experience a head injury are at an increased risk of intracranial haemorrhage[3,4]
with rates of mortality reported between 45-70%.[3,5–7] Liberal use of CT scanning is therefore
required to identify intracranial haemorrhage in these patients. However, it is not clear whether all
anticoagulated patients with head injury should receive a CT scan or whether CT should be used
selectively and limited to those with evidence of traumatic brain injury, such as those with loss of
consciousness or amnesia.[8]
Management of head injury in the UK follows guidance from the National Institute for Health and
Care Excellence (NICE). NICE guidance issued in 2007[9] recommended that patients with
coagulopathy (including those currently treated with warfarin) should undergo CT scanning only if
they report amnesia or loss of consciousness following injury. Updated guidance issued in 2014[10]
recommended that all patients having warfarin treatment should undergo CT scanning regardless of
whether they reported amnesia or loss of consciousness (Figure 1). The new guidance should
increase the number of scans performed and intracranial injuries identified but it is not clear
whether the benefits of this approach justify the costs of additional CT scanning.
The AHEAD study was an observational cohort study of patients with head injury who were taking
warfarin and presented to a hospital emergency department (ED).[11] It was undertaken when NICE
2007 guidance was in operation but before NICE 2014 guidance was issued. We aimed to use data
from the AHEAD study and decision analysis modelling to determine the cost-effectiveness of CT for
all compared to observed practice based on guidelines recommending selective CT for those with
evidence of traumatic brain injury.
Page 4 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Figure 1: NICE guidance 2007 versus 2014
METHODS
The methods for the AHEAD study are described in detail elsewhere (Mason S, Kuczawski M, Teare
MD, et al. The AHEAD Study: An observational study of anticoagulated patients who suffer head
injury. UK; 2016. Unpublished). Briefly, 3566 adults who were taking warfarin and attended the ED
of 33 hospitals in England and Scotland between September 2011 and March 2013 following head
injury were recruited. Research staff in hospital sites recorded basic demographic information,
attendance details, injury mechanism, clinical examination findings and CT results. Patients were
then followed up to 10 weeks after presentation using hospital record review and postal
questionnaire.
We identified all patients with an adverse outcome who had not received a CT scan at their initial
hospital attendance. It is this group of patients who would be expected to receive clinical benefit
NICE Guidance CG56, 2007
• CT head scan patients with any of the
following risk factors within 1 hour:
o GCS<13
o GCS<15 at 2 hours
o Open or depressed skull fracture
o Sign of fracture at base of skull
o Post-traumatic seizure
o Focal neurological deficit
o >1 episode of vomiting
o Amnesia >30minutes before impact
• CT head scan patients that have experienced
Loss of consciousness or amnesia AND any
of the following risk factors:
Within 8 hours
o Aged 65 years or over
o Dangerous mechanism of injury
Within 1 hour
o Coagulopathy
NICE Guidance CG176, 2014
• CT head scan with any of the following risk
factors within 1 hour:
o GCS<13
o GCS<15 at 2 hours
o Open or depressed skull fracture
o Any sign of basal skull fracture
o Post-traumatic seizure
o Focal neurological deficit
o >1 episode of vomiting
• CT head scan patients that have
experienced Loss of consciousness or
amnesia AND any of the following risk
factors:
Within 8 hours
o Aged 65 years or over
o History of bleeding or clotting
disorders
o Dangerous mechanism of injury
o >30 minutes retrograde amnesia of
events
• CT head scan patients with no other
indications for CT head scan AND having
warfarin treatment, within 8 hours
Page 5 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
from a policy of CT scanning all patients. An adverse outcome was defined as: death; neurosurgery;
positive CT scan finding; or re-attendance to the hospital with a significant head injury-related
complication up to 10-weeks after the original attendance. These re-attendances were confirmed
following the review of hospital records and CT scan results, where undertaken.
Decision analysis modelling was used to estimate the quality adjusted life years (QALY) and cost
implications had those patients with an adverse outcome that were not CT scanned received a CT
scan on initial hospital attendance. Different assumptions were required for patients conditional on
whether they survived the adverse event. For patients who died, assumptions were required
regarding: the probability of survival if a CT scan had been performed; the Glasgow Outcome Scale
(GOS) state to which the patient would be categorised if they survived;[11] and the cost of
neurosurgery. For patients who survived, an assumption was required relating to the probability of
GOS increase if a CT scan had been performed. Regardless of survival outcome, assumptions were
required on: the life expectancy of a person with the same gender and age profile; the costs and
utility associated with each GOS state; and the cost of a CT scan. The assumptions used within the
model are detailed below. The results presented take an English and Scottish perspective and use
direct healthcare and personal social services costs.
Model Assumptions
For patients who did not survive the adverse event:
The probability of survival if a CT scan had been performed
Two clinicians provided estimates of the probability of survival had the patient received a CT scan. In
the main analysis an average value was used, although sensitivity analyses were undertaken
assuming that each clinician was correct.
The GOS state to which the patient would be categorised if they survived
Page 6 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
A single clinician provided an estimate of the GOS of the patient if they had survived. In a sensitivity
analysis the impact of the GOS state being one level higher (that is, more favourable to the patient)
was explored.
The costs of neurosurgery
The cost of neurosurgery was assumed to be that associated with the weighted average of NHS
Reference Cost Codes AA50A – AA57B, excluding codes relating to patients aged 18 years and under,
which was £3994.[12] It was assumed that all patients who died without having a CT scan would
undergo neurosurgery.
For patients who survived the adverse event:
The probability of GOS increase if a CT scan had been performed
Two clinicians provided estimates of the probability of an increase in the GOS level, (i.e. a better
patient outcome) if a CT scan had been performed. In the main analysis an average value was used,
although sensitivity analyses were undertaken assuming that each clinician was correct.
For all patients:
The life expectancy of the person
These data were taken from UK Life Tables[13] and it was assumed that these were not affected by
an adverse event that had been survived.
The costs and utility associated with each GOS state
The data for GOS states 2-4 were taken from Pandor et al[14] with costs inflated from 2008/2009
values to 2014/15 prices using hospital and community health services indices reported in Curtis and
Burns.[15] The resultant values are provided in Table 1. For GOS state 5 it was assumed that the UK
general population utility conditional on age and sex was appropriate which was taken from Ara and
Brazier.[16]
Page 7 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Table 1: Assumed costs and utility associated with each GOS state, and assumed cost of
neurosurgery.
GOS state One-off Cost (£) Annual Costs (£) Utility value Source
2 47,674 46,595 0.00 Pandor et al[14] with
costs inflated using
Curtis and Burns[15]
3 0 37,214 0.15
4 18,837 0 0.51
5 0 0 PopulaMon Value† Assumption
† The uMlity in GOS state 5 were estimated from Ara and Brazier[16] conditional on age and sex.
The cost of a CT scan
The cost of a CT scan was assumed to be that associated with NHS Reference Cost Code RD20A,
which was £92.
The mathematical model
The model calculated the expected difference in costs and QALYs of moving from observed practice
to a strategy of CT scanning all patients. The following formulae were used in calculating the cost
and quality adjusted life years (QALY) impacts associated with provided CT scans to patients with
adverse events who did not receive a CT scan. All values were discounted at 3.5% per annum in
accordance with NICE guidelines.[17] A lifetime horizon was assumed due to potential mortality
benefits of the CT all strategy.
For patients who did not survive:
Change in costs: Average probability of survival if CT scan performed x (Life Expectancy x Cost per
year in estimated GOS state + cost of neurosurgery)
Change in QALYs: Average probability of survival if CT scan performed x (Life Expectancy x utility per
year in estimated GOS state)
For patients who did survive
Page 8 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Change in costs: Average probability of GOS increase if CT scan performed x Life Expectancy x (Cost
per year in higher GOS state – Cost per year in lower GOS state)
Change in QALYs: Average probability of GOS increase if CT scan performed x (Life Expectancy x
utility per year in higher GOS state – utility per year in lower GOS state)
RESULTS
Follow-up data were available for 3534/3566 patients (99%) in the AHEAD cohort. Details of the
cohort are published elsewhere (Mason S, Kuczawski M, Teare MD, et al. The AHEAD Study:
Managing anticoagulated patients who suffer head injury. UK; 2016. Unpublished). Glasgow
Outcome Scale and diagnosis was available for 91.4% (n=3229) and 99.9% (n=3530) patients
respectively. Overall 2114/3534 patients (60%) received a CT scan. Of the 1420 patients without a CT
scan, 728 (51%) were admitted to hospital, 20 (1.4%) had subsequent head injury related hospital
attendances, and 74 (5.2%) died during follow-up. Cause of death was head injury related in four
(0.3%), unrelated in 52 (3.7%) and unknown in 19 (1.3%). Adverse outcomes were identified in
7/1420 (0.5%) patients who did not have CT scan: four deaths and three with a related further
hospital attendance and significant finding on CT scan at re-attendance.
The estimated changes in costs and QALYs per individual patient are provided in Table 2. The
summarised analyses including the increased costs of CT scans are provided in Table 3.
Page 9 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Table 2: Estimated outcomes for patients with adverse events who were not CT scanned if they had
been CT scanned on admission to hospital and modelled implications for costs and QALYs
Patient
Outcomes Modelling
Age Sex Admitted
Observed
CT head
scan
Reversal
therapy Neurosurgery
Further
hospital
attendance
HI
Death
Probability of
survival (%) Estimated
GOS if
survived
Change
in costs
Change in
QALYs Clinician
1
Clinician
2
1 81 M � � � � � � 75 75 3 £169,279 0.67
2 74 M � � � � � � 25 15 2 £13,528 0.00
3 90 M � � � � � � 0 0 2 £3,994 0.00
4 88 M � � � � � � 75 75 4 £18,122 1.45
Probability of GOS
increase (+1, %) Lower GOS
score Δ C Δ Q
Clinician
1
Clinician
2
5 76 M � � � � � � 25 50 4 -£7,064 0.86
6 77 F � � � � � � 25 0 4 -£2,355 0.27
7 82 M � � � � � � 25 0 4 -£2,355 0.17
Table 3: The comparison of CT all with observed practice.
Change in costs from
CT scanning (£)
Change in QALYs
from CT scanning
ICER (Cost per QALY
gained (£))
Changes in individual patient values 193,149 3.41
Additional CT scanning costs 130,683
Net Values 323,832 3.41 94,895
It is estimated that the cost per QALY gained through providing a CT scan is in excess of £90,000 per
QALY which is markedly greater than the £20,000 to £30,000 per QALY gained threshold reported by
NICE.[17] This conclusion did not alter within the sensitivity analyses performed. Using the estimates
from the individual expert clinicians which produced values of £90,659 and £99,547 per QALY gained
or if the cost of neurosurgery was not included for the patient who neither expert clinician believed
would have survived even with a CT scan (£93,725 per QALY gained). When it was assumed that all
patients survived at one GOS state better than estimated in the base case the cost per QALY gained
reduced to £36,864 (an additional £213,139 to obtain 5.78 QALYs) but still did not fall below NICE
thresholds.
Page 10 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
DISCUSSION
Follow-up of 1420 patients who did not have a CT scan in the AHEAD cohort identified seven cases
(four deaths, three delayed diagnoses) that might have been identified by CT scanning at initial
hospital attendance. Decision analytic modelling showed that appropriate treatment of these cases
could have gained 3.41 QALYs but would have incurred £193,149 additional treatment costs and
£130,683 additional costs for CT scanning. This produces an incremental cost of £94,895 per QALY
gained, which is greatly above the usual threshold of £20-30,000/QALY that NICE uses to determine
cost-effectiveness. Our analysis therefore suggests that CT for all anticoagulated patients with head
injury, as recommended in NICE 2014 guidance, is not cost-effective compared to the selective use
of CT scanning observed in practice when NICE 2007 guidance was in operation.
Our analysis has a number of strengths and weaknesses. It was based upon a large representative
cohort of patients who presented to a wide range of hospitals. The methods used to estimate health
gain from treating additional cases detected by universal CT scanning are transparent and
reproducible, and were robust to the sensitivity analyses undertaken. A potential limitation is that
some patients who suffered adverse outcome may not have been identified on follow-up leading to
underestimation of the potential benefit of CT scan for all patients. However, it is worth noting that
10.79 QALYs would be required to reach the NICE threshold of £30,000/QALY for cost-effectiveness,
so our conclusion regarding the lack of cost-effectiveness of unselective CT scanning would only be
undermined if follow-up had identified less than 1 in 3 patients with adverse events. This seems
extremely unlikely. Other limitations may have underestimated the additional costs of unselective
CT scanning, for example we did not include knock-on costs from additional CT scanning, such as
those generated by incidental findings.
Most international guidance, including the National Emergency X-Radiology Utilisation Study (NEXUS
II), CT in Head Injury Patients (CHIP), American College of Emergency Physicians (ACEP) head CT and
the European Federation of Neurological Societies (EFNS)[18-21] advocate that all patients taking
Page 11 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
warfarin should have an immediate CT scan irrespective of injury severity, GCS or neurological
symptoms. The UK guidelines (NICE) are based on the Canadian CT Head Rule(CCHR)[22] which
excluded patients taking warfarin and up until January 2014, stated that a CT scan should be
performed on patients taking warfarin if the patient presented with loss of consciousness or
amnesia. These guidelines have now been updated to recommend all anticoagulated patients
receive a CT scan but no new evidence appears to have been published to support this
recommended change in practice. Our analysis suggests that the 2014 revision to NICE guidance has
resulted in less cost-effective care.
Previous literature investigating the patient outcomes and costs associated with diagnosing and
treating head injured patients who are taking anticoagulants are limited and difficult to compare to
our analysis. Several recent studies have used decision analysis modelling to estimate the costs and
benefits of CT scanning in the general (i.e. non-anticoagulated) head injured population[23-25] and
have generally shown that using a clinical decision rule to select patients for CT scanning is more
cost-effective than unselective CT scanning. The only study identified that focused solely on
anticoagulated patients was undertaken by Li in 2012.[26] Li questioned how this cohort of patients
should be managed due to the nature of delayed complications associated with anticoagulant use,
whilst also considering the costs attached to CT imaging and admittance to hospital. The analyses
were based on data taken from other studies and included repeated CT scans (2) and 24-hour
admission per patient. The costs per year of a life saved in the US, Spain and Canada were estimated
as $1 million, $158,000 and $105,000 respectively.
CONCLUSION
CT scanning for all anticoagulated patients with head injury is not cost-effective compared with
selective use of CT scanning based on guidelines recommending scanning only for those with
evidence of traumatic brain injury. A move (or return to) selective use of CT scanning would
Page 12 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
substantially reduce health care costs with only a small increase in potentially avoidable adverse
outcomes.
Acknowledgements: We thank Rosemary Harper for her contribution as a patient representative
throughout the duration of the study; all the clinicians and research staff in the participating hospital
sites who identified patients in this study, without whose hard work this study would not have been
possible.
Contributors: All authors provided substantial contributions to the conception, design, acquisition of
the data, or analysis and interpretation of the study data. MK drafted the article and all authors
contributed to its revision for important intellectual content. All authors approved the final version.
SM is guarantor. All authors agree to be accountable for all aspects of the work ensuring that
questions related to accuracy or integrity of any party of the work are appropriately investigated and
resolved.
Transparency: SM affirms that this manuscript is an honest, accurate, and transparent account of
the study being reported; that no important aspects of the study have been omitted; and that any
discrepancies from the study as planned (and, if relevant, registered) have been explained.
Funding: This paper presents independent research commissioned by the National Institute for
Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme grant reference
number PB-PG-0808-17148. The views expressed are those of the author(s) and not necessarily
those of the NHS, the NIHR or the Department of Health.
Competing interests: All authors have completed the ICMJE uniform disclosure form at
www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted
work; no financial relationships with any organisations that might have an interest in the submitted
work in the previous three years; no other relationships or activities that could appear to have
influenced the submitted work.
Page 13 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Ethical approval: NRES Committee Yorkshire and The Humber – Sheffield: 11/H1308/13.
Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust – Ref.: STH15705.
Provenance and peer review: Not commissioned; externally peer reviewed.
Data Sharing Statement: No additional data are available.
Open Access: This is an Open Access article distributed in accordance with the terms of the Creative
Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build
upon this work, for commercial use, provided the original work is properly cited. See:
http://creativecommons.org/licenses/by/4.0/.
Page 14 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
REFERENCES
1 Kamali F, Pirmohamed M. The future prospects of pharmacogenetics in oral anticoagulation
therapy. Br J Clin Pharmacol 2006:746–51.
2 Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future
challenges. Pharmacogenomics J 2007;7(2):99–111.
3 Volans AP. The risks of minor head injury in the warfarinised patient. J Accid Emerg Med
1998;15(3):159–61.
4 Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and
hypotheses. Stroke 1995;26(8):1471–7.
5 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin.
Ann Intern Med 1994;120(11):897–902.
6 Ferrera PC, Bartfield JM. Outcomes of anticoagulated trauma patients. Am J Emerg Med
1999;17(2):154–6.
7 Mathiesen T, Benediktsdottir K, Johnsson H, et al. Intracranial traumatic and non-traumatic
haemorrhagic complications of warfarin treatment. Acta Neurol Scand 1995;91(3):208–14.
8 Leiblich a, Mason S. Emergency management of minor head injury in anticoagulated
patients. Emerg Med J 2011;28(2):115–8.
9 National Institute for Health and Care Excellence. Head injury: triage, assessment,
investigation and early management of head injury in infants, children and adults. (Clinical
Guideline 56.) London; 2007. http://www.nice.org.uk/CG56.
10 National Institute for Health and Care Excellence. Head injury: triage, assessment,
investigation and early management of head injury in infants, children and adults. (Clinical
Guideline 176.) London; 2014. http://www.nice.org.uk/CG176.
11 Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome
Scale and extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma
1998;15:573-585.
Page 15 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
12 Department of Health. National Schedule of Reference Costs 2014-15 for NHS trusts and
NHS foundation trusts. London; 2015 [Accessed January 2016]. Available from:
http://www.gov.uk/government/publications/nhs-reference-costs-2014-to-2015.
13 Office for National Statistics. National Life Tables, 2010-2012. London; 2014 [Accessed
January 2016]. Available from: http://www.ons.gov.uk/ons/publications/re-reference-
tables.html?edition=tcm%3A77-352834.
14 Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and
children with minor head injury: a systematic review and an economic evaluation. Health
Technol Assess 2011;15(27):1–196.
15 Curtis L,Burns A. Unit Costs of Health and Social Care 2015. Personal Social Services Research
Unit, Canterbury, Kent; 2015 [Accessed January 2016]. Available from:
http://www.pssru.ac.uk/project-pages/unit-costs/2015/.
16 Ara R, Brazier JE. Populating an Economic Model with Health State Utility Values: Moving
toward Better Practice. Value Health 2010;13(5):509–18.
17 National Institute for Health and Care Excellence. Guide to the methods of technology
appraisals . London; 2013 [Accessed January 2016]. Available from:
http://www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-
technology-appraisal-2013-pdf.
18 Mower WR, Hoffman JR, Herbert M, et al. Developing a clinical decision instrument to rule
out intracranial injuries in patients with minor head trauma: methodology of the NEXUS II
investigation. Ann Emerg Med 2002;40:505–14.
19 Smits M, Diederik W, Dippel W, et al. Predicting intracranial traumatic findings on computed
tomography in patients with minor head injury: the CHIP prediction rule. Ann Intern Med
2007;146:397-405.
20 Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in
adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008;52:714-748.
Page 16 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
21 Vos PE, Battistin L, Girbamer G, et al. EFNS guideline on mild traumatic brain injury: report of
an EFNS task force. Eur J Neurol 2002;9:207-219.
22 Stiell IG, Wells GA, Vandemheen K, et al. The Canadian CT head rule for patients with minor
head injury. Lancet 2001;357:1391 –1396.
23 Melnick ER, Keegan J, Taylor RA. Redefining Overuse to Include Costs: A Decision Analysis for
Computed Tomography in Minor Head Injury. Jt Comm J Qual Patient Saf 2015;41(7):313-22.
24 Smits M, Dippel DW, Nederkoorn PJ, et al. Minor head injury: CT-based strategies for
management—a cost-effectiveness analysis. Radiology 2010 Feb;254(2):532-40.
25 Holmes MW, Goodacre S, Stevenson MD, et al. The cost-effectiveness of diagnostic
management strategies for adults with minor head injury. Injury 2012;43:1423-1431.
26 Li J. Admit all anticoagulated head-injured patients? A million dollars versus your dime. You
make the call. Ann of Emerg Med 2012;59(6):457-459.
Page 17 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
CHEERS checklist - Items to include when reporting economic evaluations of health interventions
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling
of an observational cohort
Section/item Item
No Recommendation
Reported
on page
No/ line
No
Title and abstract
Title 1
Identify the study as an economic evaluation or use
more specific terms such as “cost-effectiveness
analysis”, and describe the interventions compared.
1
Abstract 2
Provide a structured summary of objectives,
perspective, setting, methods (including study design
and inputs), results (including base case and
uncertainty analyses), and conclusions.
2
Introduction
Background and objectives 3
Provide an explicit statement of the broader context
for the study. 4
Present the study question and its relevance for
health policy or practice decisions. 4
Methods
Target population and
subgroups 4
Describe characteristics of the base case population
and subgroups analysed, including why they were
chosen.
5
Setting and location 5 State relevant aspects of the system(s) in which the
decision(s) need(s) to be made. 5
Study perspective 6 Describe the perspective of the study and relate this
to the costs being evaluated. 6
Comparators 7 Describe the interventions or strategies being
compared and state why they were chosen. 4
Time horizon 8
State the time horizon(s) over which costs and
consequences are being evaluated and say why
appropriate.
8
Discount rate 9 Report the choice of discount rate(s) used for costs
and outcomes and say why appropriate. 8
Choice of health outcomes 10
Describe what outcomes were used as the
measure(s) of benefit in the evaluation and their
relevance for the type of analysis performed.
6,10
Measurement of effectiveness 11a
Single study-based estimates: Describe fully the
design features of the single effectiveness study and
why the single study was a sufficient source of
clinical effectiveness data.
4
Page 18 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
11b
Synthesis-based estimates: Describe fully the
methods used for identification of included studies
and synthesis of clinical effectiveness data.
N/A
Measurement and valuation of
preference based outcomes 12
If applicable, describe the population and methods
used to elicit preferences for outcomes. N/A
Estimating resources and costs
13a
Single study-based economic evaluation: Describe
approaches used to estimate resource use associated
with the alternative interventions. Describe primary
or secondary research methods for valuing each
resource item in terms of its unit cost. Describe any
adjustments made to approximate to opportunity
costs.
N/A
13b
Model-based economic evaluation: Describe
approaches and data sources used to estimate
resource use associated with model health states.
Describe primary or secondary research methods for
valuing each resource item in terms of its unit cost.
Describe any adjustments made to approximate to
opportunity costs.
7-8
Currency, price date, and
conversion 14
Report the dates of the estimated resource
quantities and unit costs. Describe methods for
adjusting estimated unit costs to the year of reported
costs if necessary. Describe methods for converting
costs into a common currency base and the exchange
rate.
7
Choice of model 15
Describe and give reasons for the specific type of
decision-analytical model used. Providing a figure to
show model structure is strongly recommended.
8
Assumptions 16 Describe all structural or other assumptions
underpinning the decision-analytical model. 5-8
Analytical methods 17
Describe all analytical methods supporting the
evaluation. This could include methods for dealing
with skewed, missing, or censored data;
extrapolation methods; methods for pooling data;
approaches to validate or make adjustments (such as
half cycle corrections) to a model; and methods for
handling population heterogeneity and uncertainty.
5-8
Results
Study parameters 18
Report the values, ranges, references, and, if used,
probability distributions for all parameters. Report
reasons or sources for distributions used to
represent uncertainty where appropriate. Providing a
table to show the input values is strongly
recommended.
6-8
Incremental costs and
outcomes 19
For each intervention, report mean values for the
main categories of estimated costs and outcomes of
interest, as well as mean differences between the
comparator groups. If applicable, report incremental
cost-effectiveness ratios.
10
Page 19 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Characterising uncertainty
20a
Single study-based economic evaluation: Describe
the effects of sampling uncertainty for the estimated
incremental cost and incremental effectiveness
parameters, together with the impact of
methodological assumptions (such as discount rate,
study perspective).
20b
Model-based economic evaluation: Describe the
effects on the results of uncertainty for all input
parameters, and uncertainty related to the structure
of the model and assumptions.
10
Characterising heterogeneity 21
If applicable, report differences in costs, outcomes,
or cost-effectiveness that can be explained by
variations between subgroups of patients with
different baseline characteristics or other observed
variability in effects that are not reducible by more
information.
N/A
Discussion
Study findings, limitations,
generalisability, and current
knowledge
22
Summarise key study findings and describe how they
support the conclusions reached. Discuss limitations
and the generalisability of the findings and how the
findings fit with current knowledge.
10-12
Other
Source of funding 23
Describe how the study was funded and the role of
the funder in the identification, design, conduct, and
reporting of the analysis. Describe other non-
monetary sources of support.
13
Conflicts of interest 24
Describe any potential for conflict of interest of study
contributors in accordance with journal policy. In the
absence of a journal policy, we recommend authors
comply with International Committee of Medical
Journal Editors recommendations.
13
Page 20 of 20
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling of an observational
cohort
Journal: BMJ Open
Manuscript ID bmjopen-2016-013742.R1
Article Type: Research
Date Submitted by the Author: 24-Oct-2016
Complete List of Authors: Kuczawski, Maxine; University of Sheffield School of Health and Related Research, School of Health and Health Related Research Stevenson, Matt; University of Sheffield School of Health and Related
Research, School of Health and Health Related Research Goodacre, Steve; University of Sheffield, Medical Care Research Unit Teare, M; University of Sheffield, School of Health and Related Research Ramlakhan, Shammi; Northern General Hospital, Emergency Department Morris, Francis; Northern General Hospital, Emergency Department mason, suzanne; university of sheffield, UK, school of health and related research
<b>Primary Subject Heading</b>:
Emergency medicine
Secondary Subject Heading: Health economics, Health policy, Radiology and imaging, Neurology
Keywords: Anticoagulation < HAEMATOLOGY, Head & neck imaging < RADIOLOGY & IMAGING, TRAUMA MANAGEMENT, Warfarin
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open on O
ctober 18, 2020 by guest. Protected by copyright.
http://bmjopen.bm
j.com/
BM
J Open: first published as 10.1136/bm
jopen-2016-013742 on 13 Decem
ber 2016. Dow
nloaded from
For peer review only
1
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling 1
of an observational cohort 2
Maxine Kuczawski, Matt Stevenson, Steve Goodacre, M Dawn Teare, Shammi Ramlakhan, Francis 3
Morris, Suzanne Mason 4
Maxine Kuczawski, School of Health and Related Research, University of Sheffield, Sheffield UK 5
Professor Matt Stevenson, School of Health and Related Research, University of Sheffield, Sheffield 6
UK 7
Professor Steve Goodacre, School of Health and Related Research, University of Sheffield, Sheffield 8
UK 9
MD Teare, School of Health and Related Research, University of Sheffield, Sheffield UK 10
Dr Shammi Ramlakhan, Emergency Department, Northern General Hospital, Sheffield UK 11
Dr Francis Morris, Emergency Department, Northern General Hospital, Sheffield UK 12
Professor Suzanne Mason, School of Health and Related Research, University of Sheffield, Sheffield 13
UK 14
Corresponding author: Professor Suzanne Mason 15
School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, 16
Sheffield S1 4DA; [email protected]; 0114 222 0694 17
Word count: 2911 (excluding title page, abstract, references, tables and figures) 18
19
Page 1 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
2
ABSTRACT 1
Objectives: It is not currently clear whether all anticoagulated patients with a head injury should 2
receive CT scanning or only those with evidence of traumatic brain injury (e.g. loss of consciousness 3
or amnesia). We aimed to determine the cost-effectiveness of CT for all compared to selective CT 4
use for anticoagulated patients with a head injury. 5
Design: Decision-analysis modelling of data from a multi-centre observational study. 6
Setting: 33 Emergency Departments in England and Scotland. 7
Participants: 3566 adults (aged ≥16 years) who had suffered blunt head injury, were taking warfarin 8
and underwent selective CT scanning. 9
Main outcome measures: Estimated expected benefits in terms of quality-adjusted life years 10
(QALYs) were the entire cohort to receive a CT scan; estimated increased costs of CT and also the 11
potential cost implications associated with patient survival and improved health. These values were 12
used to estimate the cost per QALY of implementing a strategy of CT for all patients compared to 13
observed practice based on guidelines recommending selective CT use. 14
Results: Of the 1420/3534 patients (40%) who did not receive a CT scan, 7 (0.5%) suffered a 15
potentially avoidable head injury related adverse outcome. If CT scanning had been performed in all 16
patients, appropriate treatment could have gained 3.41 additional quality-adjusted life years (QALYs) 17
but would have incurred £193,149 additional treatment costs and £130,683 additional CT costs. The 18
incremental cost-effectiveness ratio of £94,895/QALY gained for unselective compared to selective 19
CT use is markedly above the threshold of £20-30,000/QALY used by the UK National Institute for 20
Care Excellence to determine cost-effectiveness. 21
Conclusions: CT scanning for all anticoagulated patients with head injury is not cost-effective 22
compared with selective use of CT scanning based on guidelines recommending scanning only for 23
those with evidence of traumatic brain injury. 24
Page 2 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
3
Trial registration ClinicalTrials.gov NCT 02461498. 1
ARTICLE SUMMARY 2
Strengths and limitations of this study 3
• This is the largest study to model options for the clinical management of anticoagulated 4
patients taking warfarin with a head injury. 5
• The methods used to estimate health gain from treating additional cases detected by 6
universal CT scanning are transparent and reproducible, and were robust to the sensitivity 7
analyses undertaken. 8
• Some patients who suffered adverse outcome may not have been identified on follow-up 9
potentially being a limitation of the study, leading to underestimation of the potential 10
benefit of CT scan for all patients. 11
12
Page 3 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
4
BACKGROUND 1
It is estimated that at least 1% of the United Kingdom (UK) population are taking an anticoagulant, 2
such as warfarin, increasing to 8% in those aged 80 years and over[1, 2]. People taking an 3
anticoagulant who experience a head injury are at an increased risk of intracranial haemorrhage[3,4] 4
with rates of mortality reported between 45-70%.[3,5–7] Liberal use of CT scanning is therefore 5
required to identify intracranial haemorrhage in these patients. However, it is not clear whether all 6
anticoagulated patients with head injury should receive a CT scan or whether CT should be used 7
selectively and limited to those with evidence of traumatic brain injury, such as those with loss of 8
consciousness or amnesia.[8] 9
Management of head injury in the UK follows guidance from the National Institute for Health and 10
Care Excellence (NICE). NICE guidance issued in 2007[9] recommended that patients with 11
coagulopathy (including those currently treated with warfarin) should undergo CT scanning only if 12
they report amnesia or loss of consciousness following injury. Updated guidance issued in 2014[10] 13
recommended that all patients having warfarin treatment should undergo CT scanning regardless of 14
whether they reported amnesia or loss of consciousness (Figure 1). The new guidance should 15
increase the number of scans performed and intracranial injuries identified but it is not clear 16
whether the benefits of this approach justify the costs of additional CT scanning. 17
The AHEAD study was an observational cohort study of patients with head injury who were taking 18
warfarin and presented to a hospital emergency department (ED).[11] It was undertaken when NICE 19
2007 guidance was in operation but before NICE 2014 guidance was issued. We aimed to use data 20
from the AHEAD study and decision analysis modelling to determine the cost-effectiveness of CT for 21
all compared to observed practice based on guidelines recommending selective CT for those with 22
evidence of traumatic brain injury. 23
24
25
Page 4 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
5
METHODS 1
The methods for the AHEAD study are described in detail elsewhere.[11] Briefly, 3566 adults who 2
were taking warfarin and attended the ED of 33 hospitals in England and Scotland between 3
September 2011 and March 2013 following head injury were recruited. Research staff in hospital 4
sites recorded basic demographic information, attendance details, injury mechanism, clinical 5
examination findings and CT results. Patients were then followed up to 10 weeks after presentation 6
using hospital record review and postal questionnaire. 7
We identified all patients with an adverse outcome who had not received a CT scan at their initial 8
hospital attendance. The patients that did receive a CT scan (under a selective CT scanning policy) 9
would receive the same treatment if a CT scan all policy was in place, therefore it is the former group 10
of patients who would be expected to receive clinical benefit from a policy of CT scanning all 11
patients. However, a threshold analysis was conducted to estimate the proportion of inpatient 12
attendances of less than 48 hours that would need to be avoided for the CT scan all policy to have a 13
cost per quality adjusted life year (QALY) below £30,000, assuming the cost of such an inpatient stay 14
to be that associated with a non-elective inpatient stay (£615)[12]. An adverse outcome was defined 15
as: death; neurosurgery; positive CT scan finding; or re-attendance to the hospital with a significant 16
head injury-related complication up to 10-weeks after the original attendance. These re-attendances 17
were confirmed following the review of hospital records and CT scan results, where undertaken. 18
Decision analysis modelling was used to estimate the incremental QALYs and costs had those 19
patients with an adverse outcome that were not CT scanned received a CT scan on initial hospital 20
attendance. Different assumptions were required for patients conditional on whether they survived 21
the adverse event. For patients who died, assumptions were required regarding: the probability of 22
survival if a CT scan had been performed; the Glasgow Outcome Scale (GOS) state to which the 23
patient would be categorised if they survived;[13] and the cost of neurosurgery. For patients who 24
survived, an assumption was required relating to the probability of GOS increase if a CT scan had 25
Page 5 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
6
been performed. Regardless of survival outcome, assumptions were required on: the life expectancy 1
of a person with the same gender and age profile; the costs and utility associated with each GOS 2
state; and the cost of a CT scan. The assumptions used within the model are detailed below. The 3
results presented take an English and Scottish perspective and use direct healthcare and personal 4
social services costs. 5
Model Assumptions 6
For patients who did not survive the adverse event: 7
The probability of survival if a CT scan had been performed 8
Two clinicians provided estimates of the probability of survival had the patient received a CT scan. In 9
the main analysis an average value was used, although sensitivity analyses were undertaken 10
assuming that each clinician was correct. 11
The GOS state to which the patient would be categorised if they survived 12
A single clinician provided an estimate of the GOS of the patient if they had survived. In a sensitivity 13
analysis the impact of the GOS state being one level higher (that is, more favourable to the patient) 14
was explored. 15
The costs of neurosurgery 16
The cost of neurosurgery was assumed to be that associated with the weighted average of NHS 17
Reference Cost Codes AA50A – AA57B, excluding codes relating to patients aged 18 years and under, 18
which was £3994.[14] It was assumed that all patients who died without having a CT scan would 19
undergo neurosurgery. 20
For patients who survived the adverse event: 21
The probability of GOS increase if a CT scan had been performed 22
Page 6 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
7
Two clinicians provided estimates of the probability of an increase in the GOS level, (i.e. a better 1
patient outcome) if a CT scan had been performed. In the main analysis an average value was used, 2
although sensitivity analyses were undertaken assuming that each clinician was correct. 3
For all patients: 4
The life expectancy of the person 5
These data were taken from UK Life Tables[15] and it was assumed that these were not affected by 6
an adverse event that had been survived. 7
The costs and utility associated with each GOS state 8
The data for GOS states 2-4 were taken from Pandor et al[16] with costs inflated from 2008/2009 9
values to 2014/15 prices using hospital and community health services indices reported in Curtis and 10
Burns.[12] The resultant values are provided in Table 1. For GOS state 5 it was assumed that the UK 11
general population utility conditional on age and sex was appropriate which was taken from Ara and 12
Brazier.[17] 13
Table 1: Assumed costs and utility associated with each GOS state, and assumed cost of 14
neurosurgery. 15
GOS state One-off Cost (£) Annual Costs (£) Utility value Source
2 47,674 46,595 0.00 Pandor et al[16] with
costs inflated using
Curtis and Burns[12]
3 0 37,214 0.15
4 18,837 0 0.51
5 0 0 PopulaKon Value† Assumption
† The uKlity in GOS state 5 were esKmated from Ara and Brazier[17] conditional on age and sex. 16
The cost of a CT scan 17
The cost of a CT scan was assumed to be that associated with NHS Reference Cost Code RD20A, 18
which was £92. 19
The mathematical model 20
Page 7 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
8
The model calculated the expected difference in costs and QALYs of moving from observed practice 1
to a strategy of CT scanning all patients. The following formulae were used in calculating the cost 2
and quality adjusted life years (QALY) impacts associated with provided CT scans to patients with 3
adverse events who did not receive a CT scan. All values were discounted at 3.5% per annum in 4
accordance with NICE guidelines.[18] A lifetime horizon was assumed due to potential mortality 5
benefits of the CT all strategy. 6
For patients who did not survive: 7
Change in costs: Average probability of survival if CT scan performed x (Life Expectancy x Cost per 8
year in estimated GOS state + cost of neurosurgery) 9
Change in QALYs: Average probability of survival if CT scan performed x (Life Expectancy x utility per 10
year in estimated GOS state) 11
For patients who did survive 12
Change in costs: Average probability of GOS increase if CT scan performed x Life Expectancy x (Cost 13
per year in higher GOS state – Cost per year in lower GOS state) 14
Change in QALYs: Average probability of GOS increase if CT scan performed x (Life Expectancy x 15
utility per year in higher GOS state – utility per year in lower GOS state) 16
RESULTS 17
Follow-up data were available for 3534/3566 patients (99%) in the AHEAD cohort. Details of the 18
cohort are published.[11] Glasgow Outcome Scale and diagnosis was available for 91.4% (n=3229) 19
and 99.9% (n=3530) patients respectively. Overall 2114/3534 patients (60%) received a CT scan. Of 20
the 1420 patients without a CT scan, 728 (51%) were admitted to hospital, 20 (1.4%) had subsequent 21
head injury related hospital attendances, and 74 (5.2%) died during follow-up. Cause of death was 22
head injury related in four (0.3%), unrelated in 52 (3.7%) and unknown in 19 (1.3%). Adverse 23
Page 8 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
9
outcomes were identified in 7/1420 (0.5%) patients who did not have CT scan: four deaths and three 1
with a related further hospital attendance and significant finding on CT scan at re-attendance. 2
The estimated changes in costs and QALYs per individual patient are provided in Table 2. The 3
summarised analyses including the increased costs of CT scans are provided in Table 3. 4
5
Page 9 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
10
Table 2: Estimated outcomes for patients with adverse events who were not CT scanned if they had 1
been CT scanned on admission to hospital and modelled implications for costs and QALYs. 2
Pa
tie
nt
Outcomes Modelling
Age Sex Admitted INR Observed CT
head scan
Reversal
therapy Neurosurgery
Further
hospital
attendance
HI
Death
Probability of
survival (%) Estimated
GOS if
survived
Change
in costs
Change
in QALYs Clinician
1
Clinician
2
1 81 M � NP � � � � � 75 75 3 £169,279 0.67
2 74 M � NP � � � � � 25 15 2 £13,528 0.00
3 90 M � 4.4 � � � � � 0 0 2 £3,994 0.00
4 88 M � NP � � � � � 75 75 4 £18,122 1.45
Probability of GOS
increase (+1, %) Lower GOS
score Δ C Δ Q
Clinician
1
Clinician
2
5 76 M � 2.0 � � � � � 25 50 4 -£7,064 0.86
6 77 F � 3.0 � � � � � 25 0 4 -£2,355 0.27
7 82 M � 3.5 � � � � � 25 0 4 -£2,355 0.17
NP= Not performed. 3
Table 3: The comparison of CT all with observed practice. 4
Change in costs from
CT scanning (£)
Change in QALYs
from CT scanning
ICER (Cost per QALY
gained (£))
Changes in individual patient values 193,149 3.41
Additional CT scanning costs 130,683
Net Values 323,832 3.41 94,895
It is estimated that the cost per QALY gained through providing a CT scan is in excess of £90,000 per 5
QALY which is markedly greater than the £20,000 to £30,000 per QALY gained threshold reported by 6
NICE.[18] This conclusion did not alter within the sensitivity analyses performed. Using the estimates 7
from the individual expert clinicians which produced values of £90,659 and £99,547 per QALY gained 8
or if the cost of neurosurgery was not included for the patient who neither expert clinician believed 9
would have survived even with a CT scan (£93,725 per QALY gained). When it was assumed that all 10
patients survived at one GOS state better than estimated in the base case the cost per QALY gained 11
reduced to £36,864 (an additional £213,139 to obtain 5.78 QALYs) but still did not fall below NICE 12
thresholds. 13
Page 10 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
11
It was estimated that over 67% of the 537 inpatient stays of less than 48 hours observed would need 1
to be avoided in order for the CT scan all policy to have a cost per QALY of less than £30,000. 2
DISCUSSION 3
Follow-up of 1420 patients who did not have a CT scan in the AHEAD cohort identified seven cases 4
(four deaths, three delayed diagnoses) that might have been identified by CT scanning at initial 5
hospital attendance. Decision analytic modelling showed that appropriate treatment of these cases 6
could have gained 3.41 QALYs but would have incurred £193,149 additional treatment costs and 7
£130,683 additional costs for CT scanning. This produces an incremental cost of £94,895 per QALY 8
gained, which is greatly above the usual threshold of £20-30,000/QALY that NICE uses to determine 9
cost-effectiveness. Our analysis therefore suggests that CT for all anticoagulated patients with head 10
injury, as recommended in NICE 2014 guidance, is not cost-effective compared to the selective use 11
of CT scanning observed in practice when NICE 2007 guidance was in operation. 12
Our analysis has a number of strengths and weaknesses. It was based upon a large representative 13
cohort of patients who presented to a wide range of hospitals. The methods used to estimate health 14
gain from treating additional cases detected by universal CT scanning are transparent and 15
reproducible, and were robust to the sensitivity analyses undertaken. A potential limitation is that 16
some patients who suffered adverse outcome may not have been identified on follow-up leading to 17
underestimation of the potential benefit of CT scan for all patients. However, it is worth noting that 18
10.79 QALYs would be required to reach the NICE threshold of £30,000/QALY for cost-effectiveness, 19
so our conclusion regarding the lack of cost-effectiveness of unselective CT scanning would only be 20
undermined if follow-up had identified less than 1 in 3 patients with adverse events. This seems 21
extremely unlikely. 22
It is not believed that the threshold level for avoiding inpatient admissions of less than 48 hours 23
would be plausible. Due to the age and comorbidities of this cohort of patients there will be many 24
Page 11 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
12
reasons for patients being admitted irrespective of whether a CT scan was performed. These reasons 1
may be head injury-related such as observation, but are also likely to include other reasons such as 2
intercurrent infections, injuries relating to attendance (other than the head injury) and for social 3
reasons. Additionally, one could also postulate that by detecting incidental findings the additional CT 4
scans could result in additional admissions. If so, the incremental costs of the CT all strategy would 5
increase and it would become less cost-effective. We have no data to determine whether additional 6
CT scans result in more or fewer admissions. 7
Most international guidance, including the National Emergency X-Radiology Utilisation Study (NEXUS 8
II), CT in Head Injury Patients (CHIP), American College of Emergency Physicians (ACEP) head CT and 9
the European Federation of Neurological Societies (EFNS)[19-22] advocate that all patients taking 10
warfarin should have an immediate CT scan irrespective of injury severity, GCS or neurological 11
symptoms. The UK guidelines (NICE) are based on the Canadian CT Head Rule(CCHR)[23] which 12
excluded patients taking warfarin and up until January 2014, stated that a CT scan should be 13
performed on patients taking warfarin if the patient presented with loss of consciousness or 14
amnesia. These guidelines have now been updated to recommend all anticoagulated patients 15
receive a CT scan but no new evidence appears to have been published to support this 16
recommended change in practice. Our analysis suggests that the 2014 revision to NICE guidance has 17
resulted in less cost-effective care. 18
Previous literature investigating the patient outcomes and costs associated with diagnosing and 19
treating head injured patients who are taking anticoagulants are limited and difficult to compare to 20
our analysis. Several recent studies have used decision analysis modelling to estimate the costs and 21
benefits of CT scanning in the general (i.e. non-anticoagulated) head injured population[24-26] and 22
have generally shown that using a clinical decision rule to select patients for CT scanning is more 23
cost-effective than unselective CT scanning. The only study identified that focused solely on 24
anticoagulated patients was undertaken by Li in 2012.[27] Li questioned how this cohort of patients 25
Page 12 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
13
should be managed due to the nature of delayed complications associated with anticoagulant use, 1
whilst also considering the costs attached to CT imaging and admittance to hospital. The analyses 2
were based on data taken from other studies and included repeated CT scans (2) and 24-hour 3
admission per patient. The costs per year of a life saved in the US, Spain and Canada were estimated 4
as $1 million, $158,000 and $105,000 respectively. 5
Future research is needed to validate our findings on the potential benefits, harms and costs of CT 6
scanning since the introduction of NICE 2014, in addition to further work on the criteria used for 7
deciding whether a CT scan is appropriate such as the use of serum protein biomarkers. 8
CONCLUSION 9
CT scanning for all anticoagulated patients with head injury is not cost-effective compared with 10
selective use of CT scanning based on guidelines recommending scanning only for those with 11
evidence of traumatic brain injury. A move (or return to) selective use of CT scanning would 12
substantially reduce health care costs with only a small increase in potentially avoidable adverse 13
outcomes. 14
Acknowledgements: We thank Rosemary Harper for her contribution as a patient representative 15
throughout the duration of the study; all the clinicians and research staff in the participating hospital 16
sites who identified patients in this study, without whose hard work this study would not have been 17
possible. 18
Contributors: All authors provided substantial contributions to the conception, design, acquisition of 19
the data, or analysis and interpretation of the study data. MK drafted the article and all authors 20
contributed to its revision for important intellectual content. All authors approved the final version. 21
SM is guarantor. All authors agree to be accountable for all aspects of the work ensuring that 22
questions related to accuracy or integrity of any party of the work are appropriately investigated and 23
resolved. 24
Page 13 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
14
Transparency: SM affirms that this manuscript is an honest, accurate, and transparent account of 1
the study being reported; that no important aspects of the study have been omitted; and that any 2
discrepancies from the study as planned (and, if relevant, registered) have been explained. 3
Funding: This paper presents independent research commissioned by the National Institute for 4
Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme grant reference 5
number PB-PG-0808-17148. The views expressed are those of the author(s) and not necessarily 6
those of the NHS, the NIHR or the Department of Health. 7
Competing interests: All authors have completed the ICMJE uniform disclosure form at 8
www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted 9
work; no financial relationships with any organisations that might have an interest in the submitted 10
work in the previous three years; no other relationships or activities that could appear to have 11
influenced the submitted work. 12
Ethical approval: NRES Committee Yorkshire and The Humber – Sheffield: 11/H1308/13. 13
Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust – Ref.: STH15705. 14
Provenance and peer review: Not commissioned; externally peer reviewed. 15
Data Sharing Statement: No additional data are available. 16
Open Access: This is an Open Access article distributed in accordance with the terms of the Creative 17
Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build 18
upon this work, for commercial use, provided the original work is properly cited. See: 19
http://creativecommons.org/licenses/by/4.0/. 20
REFERENCES 21
Page 14 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
15
1 Kamali F, Pirmohamed M. The future prospects of pharmacogenetics in oral anticoagulation 1
therapy. Br J Clin Pharmacol 2006:746–51. 2
2 Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future 3
challenges. Pharmacogenomics J 2007;7(2):99–111. 4
3 Volans AP. The risks of minor head injury in the warfarinised patient. J Accid Emerg Med 5
1998;15(3):159–61. 6
4 Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and 7
hypotheses. Stroke 1995;26(8):1471–7. 8
5 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. 9
Ann Intern Med 1994;120(11):897–902. 10
6 Ferrera PC, Bartfield JM. Outcomes of anticoagulated trauma patients. Am J Emerg Med 11
1999;17(2):154–6. 12
7 Mathiesen T, Benediktsdottir K, Johnsson H, et al. Intracranial traumatic and non-traumatic 13
haemorrhagic complications of warfarin treatment. Acta Neurol Scand 1995;91(3):208–14. 14
8 Leiblich a, Mason S. Emergency management of minor head injury in anticoagulated 15
patients. Emerg Med J 2011;28(2):115–8. 16
9 National Institute for Health and Care Excellence. Head injury: triage, assessment, 17
investigation and early management of head injury in infants, children and adults. (Clinical 18
Guideline 56.) London; 2007. http://www.nice.org.uk/CG56. 19
10 National Institute for Health and Care Excellence. Head injury: triage, assessment, 20
investigation and early management of head injury in infants, children and adults. (Clinical 21
Guideline 176.) London; 2014. http://www.nice.org.uk/CG176. 22
11 Mason S, Kuczawski M, Teare MD, et al. The AHEAD Study: An evaluation of the 23
management of anticoagulated patients who suffer head injury. UK; 2016. Unpublished. 24
Page 15 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
16
12 Curtis L, Burns A. Unit Costs of Health and Social Care 2015. Personal Social Services 1
Research Unit, Canterbury, Kent; 2015 [Accessed January 2016]. Available from: 2
http://www.pssru.ac.uk/project-pages/unit-costs/2015. 3
13 Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome 4
Scale and extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 5
1998;15:573-585. 6
14 Department of Health. National Schedule of Reference Costs 2014-15 for NHS trusts and 7
NHS foundation trusts. London; 2015 [Accessed January 2016]. Available from: 8
http://www.gov.uk/government/publications/nhs-reference-costs-2014-to-2015. 9
15 Office for National Statistics. National Life Tables, 2010-2012. London; 2014 [Accessed 10
January 2016]. Available from: http://www.ons.gov.uk/ons/publications/re-reference-11
tables.html?edition=tcm%3A77-352834. 12
16 Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and 13
children with minor head injury: a systematic review and an economic evaluation. Health 14
Technol Assess 2011;15(27):1–196. 15
17 Ara R, Brazier JE. Populating an Economic Model with Health State Utility Values: Moving 16
toward Better Practice. Value Health 2010;13(5):509–18. 17
18 National Institute for Health and Care Excellence. Guide to the methods of technology 18
appraisals . London; 2013 [Accessed January 2016]. Available from: 19
http://www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-20
technology-appraisal-2013-pdf. 21
19 Mower WR, Hoffman JR, Herbert M, et al. Developing a clinical decision instrument to rule 22
out intracranial injuries in patients with minor head trauma: methodology of the NEXUS II 23
investigation. Ann Emerg Med 2002;40:505–14. 24
Page 16 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
17
20 Smits M, Diederik W, Dippel W, et al. Predicting intracranial traumatic findings on computed 1
tomography in patients with minor head injury: the CHIP prediction rule. Ann Intern Med 2
2007;146:397-405. 3
21 Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in 4
adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008;52:714-748. 5
22 Vos PE, Battistin L, Girbamer G, et al. EFNS guideline on mild traumatic brain injury: report of 6
an EFNS task force. Eur J Neurol 2002;9:207-219. 7
23 Stiell IG, Wells GA, Vandemheen K, et al. The Canadian CT head rule for patients with minor 8
head injury. Lancet 2001;357:1391 –1396. 9
24 Melnick ER, Keegan J, Taylor RA. Redefining Overuse to Include Costs: A Decision Analysis for 10
Computed Tomography in Minor Head Injury. Jt Comm J Qual Patient Saf 2015;41(7):313-22. 11
25 Smits M, Dippel DW, Nederkoorn PJ, et al. Minor head injury: CT-based strategies for 12
management—a cost-effectiveness analysis. Radiology 2010 Feb;254(2):532-40. 13
26 Holmes MW, Goodacre S, Stevenson MD, et al. The cost-effectiveness of diagnostic 14
management strategies for adults with minor head injury. Injury 2012;43:1423-1431. 15
27 Li J. Admit all anticoagulated head-injured patients? A million dollars versus your dime. You 16
make the call. Ann of Emerg Med 2012;59(6):457-459. 17
Page 17 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Figure 1: NICE guidance 2007 versus 2014
Figure 1
79x59mm (300 x 300 DPI)
Page 18 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
CHEERS checklist - Items to include when reporting economic evaluations of health interventions
Should all anticoagulated patients with head injury receive a CT scan? Decision-analysis modelling
of an observational cohort
Section/item Item
No Recommendation
Reported
on page
No/ line
No
Title and abstract
Title 1
Identify the study as an economic evaluation or use
more specific terms such as “cost-effectiveness
analysis”, and describe the interventions compared.
1
Abstract 2
Provide a structured summary of objectives,
perspective, setting, methods (including study design
and inputs), results (including base case and
uncertainty analyses), and conclusions.
2
Introduction
Background and objectives 3
Provide an explicit statement of the broader context
for the study. 4
Present the study question and its relevance for
health policy or practice decisions. 4
Methods
Target population and
subgroups 4
Describe characteristics of the base case population
and subgroups analysed, including why they were
chosen.
5
Setting and location 5 State relevant aspects of the system(s) in which the
decision(s) need(s) to be made. 5
Study perspective 6 Describe the perspective of the study and relate this
to the costs being evaluated. 6
Comparators 7 Describe the interventions or strategies being
compared and state why they were chosen. 4
Time horizon 8
State the time horizon(s) over which costs and
consequences are being evaluated and say why
appropriate.
8
Discount rate 9 Report the choice of discount rate(s) used for costs
and outcomes and say why appropriate. 8
Choice of health outcomes 10
Describe what outcomes were used as the
measure(s) of benefit in the evaluation and their
relevance for the type of analysis performed.
6,10
Measurement of effectiveness 11a
Single study-based estimates: Describe fully the
design features of the single effectiveness study and
why the single study was a sufficient source of
clinical effectiveness data.
4
Page 19 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
11b
Synthesis-based estimates: Describe fully the
methods used for identification of included studies
and synthesis of clinical effectiveness data.
N/A
Measurement and valuation of
preference based outcomes 12
If applicable, describe the population and methods
used to elicit preferences for outcomes. N/A
Estimating resources and costs
13a
Single study-based economic evaluation: Describe
approaches used to estimate resource use associated
with the alternative interventions. Describe primary
or secondary research methods for valuing each
resource item in terms of its unit cost. Describe any
adjustments made to approximate to opportunity
costs.
N/A
13b
Model-based economic evaluation: Describe
approaches and data sources used to estimate
resource use associated with model health states.
Describe primary or secondary research methods for
valuing each resource item in terms of its unit cost.
Describe any adjustments made to approximate to
opportunity costs.
7-8
Currency, price date, and
conversion 14
Report the dates of the estimated resource
quantities and unit costs. Describe methods for
adjusting estimated unit costs to the year of reported
costs if necessary. Describe methods for converting
costs into a common currency base and the exchange
rate.
7
Choice of model 15
Describe and give reasons for the specific type of
decision-analytical model used. Providing a figure to
show model structure is strongly recommended.
8
Assumptions 16 Describe all structural or other assumptions
underpinning the decision-analytical model. 5-8
Analytical methods 17
Describe all analytical methods supporting the
evaluation. This could include methods for dealing
with skewed, missing, or censored data;
extrapolation methods; methods for pooling data;
approaches to validate or make adjustments (such as
half cycle corrections) to a model; and methods for
handling population heterogeneity and uncertainty.
5-8
Results
Study parameters 18
Report the values, ranges, references, and, if used,
probability distributions for all parameters. Report
reasons or sources for distributions used to
represent uncertainty where appropriate. Providing a
table to show the input values is strongly
recommended.
6-8
Incremental costs and
outcomes 19
For each intervention, report mean values for the
main categories of estimated costs and outcomes of
interest, as well as mean differences between the
comparator groups. If applicable, report incremental
cost-effectiveness ratios.
10
Page 20 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from
For peer review only
Characterising uncertainty
20a
Single study-based economic evaluation: Describe
the effects of sampling uncertainty for the estimated
incremental cost and incremental effectiveness
parameters, together with the impact of
methodological assumptions (such as discount rate,
study perspective).
20b
Model-based economic evaluation: Describe the
effects on the results of uncertainty for all input
parameters, and uncertainty related to the structure
of the model and assumptions.
10
Characterising heterogeneity 21
If applicable, report differences in costs, outcomes,
or cost-effectiveness that can be explained by
variations between subgroups of patients with
different baseline characteristics or other observed
variability in effects that are not reducible by more
information.
N/A
Discussion
Study findings, limitations,
generalisability, and current
knowledge
22
Summarise key study findings and describe how they
support the conclusions reached. Discuss limitations
and the generalisability of the findings and how the
findings fit with current knowledge.
10-12
Other
Source of funding 23
Describe how the study was funded and the role of
the funder in the identification, design, conduct, and
reporting of the analysis. Describe other non-
monetary sources of support.
13
Conflicts of interest 24
Describe any potential for conflict of interest of study
contributors in accordance with journal policy. In the
absence of a journal policy, we recommend authors
comply with International Committee of Medical
Journal Editors recommendations.
13
Page 21 of 21
For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml
BMJ Open
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960
on October 18, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2016-013742 on 13 D
ecember 2016. D
ownloaded from