SUPPLEMENTARY MATERIAL
Supplementary Table S1: Search terms used in each of the databases.
Database
Medline®
Embase
“CDI” related search terms
exp Clostridium difficile/ OR exp
Clostridium/ OR exp Clostridium
Infections/ OR clostridium difficile.mp.
OR difficile.mp. OR Cdifficile.mp. OR (C
adj difficile).mp. OR difficile
clostridium.mp. OR Cdiff.mp. OR (C adj
diff).mp.
“Cost” related search terms
exp Economics/ OR Economics.mp. OR exp "costs and cost
analysis"/ OR (cost$ adj analysis).mp. OR exp Cost allocation/
OR cost allocation.mp. OR exp "Cost-benefit analysis"/ OR
(cost-benefit adj analysis).mp. OR exp Cost control/ OR cost
control.mp. OR exp Cost savings/ OR cost savings.mp. OR exp
"Cost of illness"/ OR (cost adj2 illness).mp. OR exp Cost
sharing/ OR cost sharing.mp. exp "deductibles and
coinsurance"/ OR (deductibles adj coinsurance).mp. OR exp
Medical savings accounts/ OR medical savings accounts.mp.
OR exp Health care costs/ OR health care costs.mp. OR exp
Direct service costs/ OR Direct service costs.mp. OR exp Drug
costs/ OR drug costs.mp. OR exp Employer health costs/ OR
Employer health costs.mp. OR exp Hospital costs/ OR hospital
costs.mp. OR exp Health expenditures/ OR Health
expenditures.mp. OR exp Capital expenditures/ OR Capital
expenditures.mp. OR exp "Value of life"/ OR (value adj
life).mp. OR exp economics, hospital/ OR exp economics,
medical/ OR exp Economics, nursing/ OR exp OR Economics,
pharmaceutical/ OR exp "fees and charges"/ OR exp budgets/
OR (low adj cost).mp. OR (high adj cost).mp. OR (health?care
adj cost$).mp. OR (fiscal or funding or financial or finance).tw.
OR (cost adj estimate$).mp. OR (unit adj cost$).mp. OR
(economic$ or pharmacoeconomic$ or price$ or pricing).tw.
OR (cost adj variable).mp. OR (cost-effect* or "cost
effect*").mp. OR exp Quality-Adjusted Life Years/ OR qualityadjusted life years.mp. OR quality adjusted life years.mp. OR
qaly.mp. OR (life adj years).mp. OR cost utili*.mp. OR (cost
adj2 utili*).mp. OR (cost adj2 effect*).mp. OR exp models,
economic/ OR (economic$ adj2 model$).mp. OR (cost adj2
utilit*).mp. OR (cost adj2 consequenc*).mp. OR net
benefit.mp. OR (willingness adj2 pay).mp.
Health
Technology
Assessment
Database
NHS Economic
Evaluation
Database
Clostridium difficile
None
CostEffectiveness
Analysis
Registry
EconLit
CDI - C. difficile infection, NHS – National Health Service
1
Supplementary Table S2: Quality assessment tool and how it was applied the COI studies.
The application of each question to a COI study
Section(s) in
which the item
should be found
Answer
options
1. The research question is
stated
 Does the objective state that the economic impact of
the disease is being determined? Examples of other
terms that can be used include: cost, expenses,
economic burden, financial impact
 If the actual disease (e.g., CDI) is not mentioned in the
objective but represented within a group of diseases
(e.g., hospital acquired infections), then put
“partially”
Objective
Y
N
P
2. The economic
importance of the
research question is
stated
 If question 1 is "yes" or “partially” then is the
rationale behind the cost analysis stated?
 If question 1 is "no" then put “not applicable”
Introduction
Objective
Y
N
NA
Introduction
Objective
Y
N
P
Objective
Methods
Y
N
P
 Does the study state which cost outcomes are being
evaluated? For example, cost per patient, cost per
episode, total cost
Methods
Results
Y
N
 Does the study provide details on the sample
population in which the costs are being obtained
from? For example, demographics
Results
Y
N
 Does the study evaluate indirect costs?
Objective
Methods
Y
N
NA
 If question 7 is "yes" then answer "yes" or "no"
 If question 7 is "no" then put "not applicable"
Introduction
Objective
Methods
Discussion
Y
N
NA
 Are resource utilization variables reported separately
from their costs? For example, if hospitalization costs
are reported, is length of stay provided? Or if
physician costs are provided, are number of physician
visits reported?
Results
Y
N
Questions from Drummond
and Jefferson (1)
3. The viewpoint(s) of the
analysis are clearly stated
and justified
4. The form of economic
evaluation used is stated
5. The primary outcome
measure(s) for the
economic evaluation are
clearly stated
6. Details of the subjects
from whom valuations
were obtained are given
7. Productivity changes (if
included) are reported
separately
8. The relevance of
productivity changes to
the study question is
discussed
9. Quantities of resources
are reported separately
from their unit costs
 Does the study state the "perspective" or "viewpoint"
of the cost analysis? Examples of perspectives
include: hospital, government, patient, insurance
company, society, caregiver
 A justification behind the perspective chosen should
also be stated
 If the perspective is only stated and not justified, then
put "partially"
 Are the epidemiological approach (e.g.,
incidence/prevalence-based approach (2, 3)) and
method of resource quantification (e.g., topdown/bottom-up approach (2, 3)) stated?
 If one or the other is stated then put “partially”
2
Questions from Drummond
and Jefferson (1)
10. Methods for the
estimation of quantities
and unit costs are
described
11. Currency and price data
are recorded
12. Time horizon of costs and
benefits is stated
The application of each question to a COI study
 Does the study describe how resource utilization and
costs are estimated? For example, are they obtained
from a survey, a database, or expert opinion?
 If the methods of either the resource utilization
variables or costs are only reported, then put
"partially"
 If the methods are discussed in the results or
discussion sections then put “partially”
 Does the study state the year and currency in which
the costs are evaluated in?
 If only one or the other is stated then put "partially"
 Does the study state the time horizon in which the
costs are evaluated over? For example, costs over
hospitalization/admission, year, lifetime
Section(s) in
which the item
should be found
Answer
options
Methods
Y
N
P
Methods
Results
Y
N
P
Methods
Results
Y
N
13. The discount rate(s) is
stated
 If future costs are calculated, are the costs
discounted?
Methods
14. The choice of rate(s) is
justified
 If question 13 is "no" then put down "not applicable"
Methods
15. An explanation is given if
costs or benefits are not
discounted
 If question 13 is "no" then put down "not applicable"
Methods
16. Details of statistical tests
and confidence intervals
are given for stochastic
data
17. The approach to
sensitivity analysis is
given
18. The choice of variables
for sensitivity analysis is
justified
19. The ranges over which
the variables are varied
are stated
20. Incremental analysis is
reported
21. Major outcomes are
presented in a
disaggregated as well as
aggregated form
22. Conclusions are
accompanied by the
appropriate caveats
 Are descriptive statistics presented for cost estimates
(e.g., mean, median, standard deviation, max, min,
range)?
 Are confidence intervals or p-values given?
 If either/or is stated, then put "partially"
 Is a sensitivity analysis conducted around costs?
 If the description of sensitivity analysis is found in the
results and discussion sections, put “partially”
Results
Methods
Y
N
NA
Y
N
NA
Y
N
NA
Y
N
P
Y
N
P
Y
N
NA
Y
N
NA
 If question 17 is "no" then put "not applicable"
Methods
 If question 17 is "no" then put "not applicable"
Methods
 Did the study mention the use of a comparison
group?
 If this is done for only part of the cohort then put
“partially”
Results
Y
N
P
 Are the costs reported by subgroups, such as sex, age,
region, resource?
Results
Y
N
 Are the limitations around the cost analysis (e.g.,
cohort, cost methods) discussed?
Discussion
Conclusions
Y
N
COI - Cost of illness; CDI - C. difficile infection; Y- Yes; N – No; P- Partially; NA- Not applicable.
3
p-value
-
-
$13,819
<0.05
Study results and
expert opinion
6w
(Jan and
Apr 1997)
LOS
Mean cost per
patient
SUM
$11,240
-
-
-
St. Paul’s Hospital
1y
(1996)
1y
Cost per
patient
SUM
$714
-
-
-
Hospitalization,
procedures,
drugs
Hannover Medical
School finance
department
1y
(2006)
LOS
Median cost
per patient
HM
-
-
$9,730
-
Hospitalization,
laboratory, drug
therapy
Antrim Area Hospital
Corporate
Information
Department
2y
LOS
Mean cost per
case
SUM
-
-
$4,124
-
Surgery,
pharmaceuticals,
laboratory,
radiology,
nursing care,
and other
Japanese Diagnosis
Procedure
Combination
database
2y
(Jul to
Dec for
each year
from
2007 to
2010)
LOS
Total costs
SUM
RA
PSM
$33,547
$33,547
$23,670
$26,580
$6,814
$6,967
<0.001
<0.001
<0.001
Bed, treatment,
laboratory
Study results,
government sources,
and expert opinion
7m
(Dec 1994
to Jun
1995)
LOS
Mean cost per
patient
SUM
-
-
$9,703
-
SUM
$40,186$78,933
-
-
-
-
-$1,522$18,563
<0.05
for
groups
1, 2,
and 5
Cost of
comparison
group
(US 2014 $)
RA
Cost of those
with CDI
(US 2014 $)
Mean cost per
episode
Type of method
to calculate
costs
Attributable
cost (US 2014 $)
Cost outcome(s)
Time horizon for
costs
LOS
Time frame of
data extraction
2y
(2005 to
2007)
Resource and
cost sources
Computerized
clinical costing
systems
Resource
utilization
variables
included
Sample size of
comparison
group
Sample size of
those with CDI
CDI definition
based on
Patient
population
Author and year
of publication
Supplementary Table S3: Summary of CDI COI studies by country.
Australia
Jackson 2011 (4)
Hospitalized
ICD code
233
-
CDI readmission
LAB, SYM
10
-
Hospitalized
LAB
100
-
Hospitalized
LAB, SYM
45
-
Hospitalized
LAB, SYM
87
-
Hospitalization
Canada
Miller 2002 (5)
Butterworth
1998 (6)
Hospitalization
and antibiotic
therapy
Laboratory and
antibiotic
therapy
Germany
Vonberg 2008
(7)
Ireland
Al-Eidan 2000
(8)
Japan
Yasunaga 2012
(9)
Hospitalized,
underwent elective
digestive tract surgery
for cancer
ICD code
Hospitalized, >65
years
LAB, SYM
143,243
409
409 (PSM)
United Kingdom
Wilcox 1996 (10)
50
92
United States
Hospitalized: 1) > 65
years; 2) renal disease;
3) cancer; 4) IBD; 5)
concomitant antibiotic
use
LAB
Jiang 2013 (12)
Hospitalized
ICD
code
1,211
6,053
Hospitalization
Pant 2013 (13)
Hospitalized, children
with IBD
ICD code
447
12,163
Hospitalization
Campbell 2013
(11)
4,521
-
Hospitalization
Health Facts
electronic health
record database
Rhode Island
Department of
Health’s Centre for
Health Data and
Analysis
Healthcare Cost and
Utilization Project
Kids’ Inpatient
Database
LOS
Mean hospital
costs
(depending on
the patient
group)
PSM
2y
(Jan 2010
to Dec
2011)
LOS
Mean costs
Median costs
PSM
$35,473
$20,998
$17,474
$9,714
$17,999
$11,284
<0.0001
-
1 year
(2009)
LOS
Mean
hospitalization
charges
RA
$46,084
$35,439
$10,644
<0.001
6 y and 2
m (Apr
2005 to
Jun 2011)
-
4
Attributable
cost (US 2014 $)
Type of method
to calculate
costs
Cost outcome(s)
Time horizon for
costs
Time frame of
data extraction
LOS
Mean
hospitalization
cost
RA
$42,027$201,174
$22,19678,878
$11,823$122,295
<0.001
Sammons 2013
(15)
Hospitalized, children,
community- and
hospital-onset of CDI
ICD code,
LAB
4,474
8,821
Hospitalization
Pediatric Health
Information System
database
5 y and 8
m (Jan
2006 to
Aug 2011)
LOS
Mean total
cost
PSM, RA
-
-
$19,207$95,118
-
$32,921
26,674
$6,247
-
1.5 y
(Jan 2007
to Jun
2008)
$21,245
$16,987
$4,258
-
Tabak 2013 (16)
Wilson 2013 (17)
Ali 2012 (18)
Kim 2012 (19)
Kuntz 2012 (20)
Hospitalized
Hospitalized,
underwent closure of
loop ileostomy
Hospitalized,
underwent liver
transplants
Hospitalized,
underwent radical
cystectomy for
bladder cancer
Patients identified
with CDI in an
outpatient and
inpatient setting
Lipp 2012 (21)
Hospitalized
McGlone 2012
(22)
Hypothetical sample,
hospitalized, >65 years
(recurrence of CDI
included in economic
model)
Pant 2012 (23)
Hospitalized,
underwent solid
organ transplants
LAB
255
765
Hospitalization
Hospitals, clinical
research database
from CareFusion,
and Centers for
Medicare and
Medicaid Services
ICD code
217
13,245
Hospitalization
Nationwide Inpatient
Sample
ICD code
5,159
193,174
Hospitalization
Nationwide Inpatient
Sample
ICD code
-
-
Hospitalization
Nationwide Inpatient
Sample
-
Emergency
department
visits,
laboratory,
pharmacy,
physician visits,
hospitalization
-
Hospitalization
-
Hospitalization,
diagnostic
procedures,
drugs, surgical
procedures, loss
in productivity
ICD code,
LAB, AT
(OPTS)
1,3161,650
ICD code
(IPTS)
ICD code
-
ICD code
-
-
-
-
Hospitalization
5y
(2004 to
2008)
5y
(2004 to
2008)
Mean cost per
case
LOS
Median cost
per case
PSM
p-value
5 y and 10
m (Jan
2005 to
Oct 2010)
Cost of
comparison
group
(US 2014 $)
HealthCore
Integrated Research
Database
Cost of those
with CDI
(US 2014 $)
Hospitalization
Resource and
cost sources
93332,799
Resource
utilization
variables
included
93310,933
Sample size of
comparison
group
Sample size of
those with CDI
ICD code
Patient
population
CDI definition
based on
Author and year
of publication
Quimbo 2013
(14)
Hospitalized: 1)
immunocompromised;
2) CDI history; 3)
concomitant antibiotic
use; 4) renal
impairment; 5) IBD; 6)
> 65 years
LOS
Mean costs
SUM
RA
$41,232
-
$17,635
-
$23,597
$20,399
<0.001
LOS
Mean hospital
charges
SUM
$148,173
$75,641
-
<0.01
8y
(2001 to
2008)
LOS
Hospitalization
cost
RA
$57,368
$32,359
-
<0.001
Kaiser Permanente
Northwest/Colorado,
Medicare and
Medicaid
3 y and 3
m (Jun
2005 to
Sept
2008)
180
d
Costs per
patient
SUM
$1,875$12,503
-
-
-
New York State
Department of
Health’s Statewide
Planning and
Research
Cooperative System
2y
(2007 to
2008)
LOS
Mean cost per
infection
RA
-
-
$30,049
-
-
-
-
$9,745$17,962
-
SUM
$55,755
$32,627
-
<0.001
RA
-
-
$72,167
<0.001
Government and
published sources
Nationwide Inpatient
Sample
-
1y
(2009)
1y
LOS
Median cost
per case
(depending on
the
perspective
and
recurrence
rate)
Median
hospital
charges
Mean hospital
charges
5
Hospitalized with endstage renal disease
ICD code
-
-
Hospitalization
Nationwide Inpatient
Sample
1y
(2009)
LOS
Peery 2012 (25)
Hospitalized
ICD code
110,553
discharges
-
Hospitalization
Nationwide Inpatient
Sample
1y
(2009)
Verlee 2012 (26)
Hospitalized
ICD code
49,516
-
Hospitalization
Michigan Health and
Hospital Association
7y
(Jan 2002
to Dec
2008)
St Luke’s Episcopal
Hospital accounting
database
1 y and 2
m (Mar
2007 to
May
2008)
Arora 2011 (27)
Hospitalized
LAB, SYM
85
-
Daily ward, ICU,
diagnostic tests,
physician visits,
other health
professionals,
pharmacy
Glance 2011 (28)
Hospitalized with
trauma
ICD code
768
148,888
Hospitalization
Nationwide Inpatient
Sample
Lesperance 2011
(29)
Hospitalized with
elective colon
resections
ICD code
10,077
695,010
Hospitalization
Nationwide Inpatient
Sample
Hospitalization
Healthcare Cost and
Utilization Project
Kids’ Inpatient
Database
Nylund 2011
(30)
Pakyz 2011 (31)
Hospitalized, children
Hospitalized
ICD code
ICD code,
AT
21,274
10,857
10,474,454
19,214
Hospital care,
laboratory, and
drugs
University Health
System Consortium
Clinical Resource
Manager program
2y
(2005 to
2006)
3y
(2004 to
2006)
4y
(1997,
2000,
2003, and
2006)
6y
(Apr 2002
to Mar
2007)
<0.001
<0.001
LOS
Median costs
SUM
$7,019
-
-
-
LOS
Mean charges
(depending on
if principal or
non-principal
diagnosis)
SUM
$27,458$90,185
-
-
-
3m
Median
hospital costs
(depending on
Horn’s index
score)
SUM
$9,080$72,667
-
-
-
LOS
Median cost
SUM
$35,212
$13,589
-
-
LOS
Hospital
charges
SUM
$141,939
$65,863
-
<0.05
LOS
LOS
Hospitalization
Nationwide Inpatient
Sample
1y
(2007)
LOS
Wang 2011 (33)
Hospitalized
ICD code
78,273
-
Hospitalization
Pennsylvania Health
Care Cost
Containment Council
4y
(2005 to
2008)
LOS
Nationwide Inpatient
Sample
1y
(2005)
LOS
Hospitalization
p-value
$65,097
41,2074,032,865
-
Attributable
cost (US 2014 $)
$58,713
-
41,207
-
Cost of
comparison
group
(US 2014 $)
$129,363
-
ICD code
ICD code
Cost of those
with CDI
(US 2014 $)
SUM
RA
Hospitalized
Hospitalized with
cirrhosis
Type of method
to calculate
costs
Mean charges
Stewart 2011
(32)
Bajaj 2010 (34)
Cost outcome(s)
Time horizon for
costs
Time frame of
data extraction
Resource and
cost sources
Resource
utilization
variables
included
Sample size of
comparison
group
Sample size of
those with CDI
CDI definition
based on
Patient
population
Author and year
of publication
Pant 2012 (24)
Median
hospitalization
charges per
patient
(depending on
the year)
Mean
hospitalization
cost
SUM
$25,544$35,437
$9,611$12,079
-
SUM
$64,720
$33,546
-
<0.001
for
1997,
2000,
and
2006
<0.001
$39,590
$15,139
RA
$63,988
$32,825
-
-
SUM
PSM
$24,689
$24,689
$9,781
$15,778
$8,911
<0.0001
$24,413
$12,005
$12,408
$12,078
$7,166
$4,913
$86,572
$38,934
-
Median
hospitalization
cost
Mean cost per
patient
Mean
hospitalization
cost
Mean hospital
cost per
admission
PSM
Median
hospital cost
per admission
Total
hospitalization
charges
RA
<0.0001
<0.001
6
Fuller 2009 (35)
Hospitalized
ICD code
-
Hospitalization
2,478
(California)
Hospitalized, DRG
127, 148, 182, 415,
and 416
-
524
7,107
-
Hospital’s private
administrative data
Zilberberg 2009
(37)
Hospitalized with
prolonged acute
mechanical ventilation
ICD code
3,370
3,36361,442
Hospitalization
Nationwide Inpatient
Sample
Hospitalized with IBD
ICD code
Dubberke 2008
(39)
Nguyen 2008
(40)
Hospitalized,
nonsurgical
Hospitalized with IBD
(Crohn’s disease and
Ulcerative colitis)
LAB
ICD code
2,804
342-439
-
77,366
34224,252
-
Hospitalization
Room and
board,
pharmacy,
laboratory,
radiology,
respiratory
therapy, physical
therapy
Hospitalization
Nationwide
Inpatient Sample
Barnes-Jewish
Hospital’s Medical
Informatics and
Trendstar financial
databases
Nationwide Inpatient
Sample
Song 2008 (41)
Hospitalized
LAB
630
630
-
John Hopkins
Hospital
administrative
finance system
Lawrence 2007
(42)
Hospitalized, ICU
LAB
75
1,760
Hospitalization
Barnes-Jewish
Hospital financial
accounting system
California:
1y
(Oct 2005
to Sept
2006)
5y
(2002 to
2006)
1y
(2005)
1y
(2003)
1y
(2003)
7y
(1998 to
2004)
4 y and 10
m
(Jan 2000
to Oct
2005)
2.5 y
(Jul 1997
to Dec
1999)
LOS
LOS
LOS
LOS
and
180
d
Mean patient
cost
Charges
(depending on
the DRG)
Mean hospital
costs
p-value
Attributable
cost (US 2014 $)
Cost of
comparison
group
(US 2014 $)
Cost of those
with CDI
(US 2014 $)
Type of method
to calculate
costs
Cost outcome(s)
Time horizon for
costs
LOS
California: Office of
Statewide Planning
and Development
Reed 2009 (36)
Ananthakrishnan
2008 (38)
Time frame of
data extraction
Resource and
cost sources
Resource
utilization
variables
included
Sample size of
those with CDI
CDI definition
based on
Patient
population
Author and year
of publication
Sample size of
comparison
group
Maryland: Health
Services and Cost
Review Commission
1,282
(Maryland)
Maryland:
1y
(Jul 2007
to Jun
2008)
Maryland:
$18,529
RA
-
-
California:
$28,167
SUM
$8,527$44,217
$5,080$26,347
-
<0.001
SUM
$82,860
$63,219
-
<0.001
Total cost
Median
hospital
charges
PSM
SUM
$21,600
$14,885
$11,483
-
-
Mean hospital
charges
Median total
costs
RA
-
$12,604
-
SUM
$17,575
$7,537
-
<0.001
Mean costs
(depending on
the time
horizon)
RA
$9,275$16,088
$6,563$10,517
$2,712$5,571
-
Median costs
(depending on
the time
horizon)
PSM
$16,099$30,259
$10,777$16,541
$3,580$7,932
-
Ulcerative
colitis:
$40,854
Ulcerative
colitis:
$27,372
-
<0.0001
Crohn’s
disease:
$39,038
Crohn’s
disease:
$23,379
Mean hospital
charges
SUM
LOS
Median costs
PSM
$22,824
$26,024
-$3,200
-
LOS
Median cost
per patient
SUM
$60,711
$24,623
-
<0.001
LOS
7
O'Brien 2007
(43)
Zerey 2007 (44)
Kyne 2002 (45)
McFarland 1999
(46)
Hospitalized
Hospitalized, surgical
Hospitalized
ICD code
ICD code
LAB. SYM
Nonprincipal
diagnosis:
2,656
8,113
-
-
1,553,597
-
Recurrent CDI
LAB, SYM
209
-
Kofsky 1991
(47)
Hospitalized
LAB
155
-
Yannelli 1988
(48)
Hospitalized,
suspected CDI
SYM
126
(positive
and
negative)
-
Hospitalization,
pharmacy,
laboratory,
imaging,
emergency
department
Massachusetts
hospital discharge
databases
Hospitalization
Nationwide Inpatient
Sample
5y
(1999 to
2003)
LOS
Hospitalization
Beth Israel
Deaconess Medical
Centre Hospital
billing system
5m
(Jan 1998
to May
1998
LOS
Medical billing
records and
laboratory charges
3y and
5m
(Aug 1993
to Dec
1996)
Hospital
-
Clinic visits,
antibiotics,
laboratory tests,
enteric pathogen
and fecal
leukocyte
examinations,
room charge,
physician visit,
and procedures
Bed, laboratory
tests, medical
treatment
Laboratory
testing
1y
(2000)
Mean cost per
stay
LOS
Median cost
per stay
Principal
diagnosis:
SUM,
nonprincipal
diagnosis:
HM
$11,717$34,377
$6,840$15,876
Nonprincipal
diagnosis:
$15,690
p-value
Attributable
cost (US 2014 $)
Cost of
comparison
group
(US 2014 $)
Cost of those
with CDI
(US 2014 $)
Type of method
to calculate
costs
Cost outcome(s)
Time horizon for
costs
Time frame of
data extraction
Resource and
cost sources
Resource
utilization
variables
included
Sample size of
comparison
group
Sample size of
those with CDI
CDI definition
based on
Patient
population
Author and year
of publication
Principal
diagnosis:
1,036
-
$6,244
Median total
charges
SUM
$72,496
$19,772
-
<0.0001
Total charges
Median
hospital cost
RA
SUM
$16,263
$7,616
$88,902
-
<0.0001
<0.0001
Hospital cost
RA
$4,852
0.003
LT
Mean per
person
SUM
$15,665
-
-
-
1y
(1988)
LOS
Mean charges
per patient
SUM
$3,764
-
-
-
1.5 y
(Jan 1986
to Jun
1987)
1.5
y
Total cost to
the hospital
SUM
$4,591
-
-
-
CDI – C. difficile infection; COI – Cost-of-illness; US – United States; ICD – International Classification of Diseases; y – Year(s); LOS – Length of stay; RA – Regression analysis; LAB – Laboratory tests (related to CDI); SYM – Symptoms (related to CDI); w – Week(s); SUM – Summation;
HM – Hard matching; PSM – Propensity score matching; m – Month(s); IBD – Inflammatory bowel disease; AT – Antibiotic therapy (vancomycin and/or metronidazole); OPTS – Outpatient setting; IPTS – Inpatient setting; d – Day(s); DRG – Diagnosis Related Groups; ICU – intensive
care unit; LT – Lifetime.
8
Supplementary Table S4: Quality assessment results.
Country
Australia
Canada
Germany
Ireland
Japan
United Kingdom
United States
Author and year
Jackson 2011 (4)
Miller 2002 (5)
Butterworth 1998 (6)
Vonberg 2008 (7)
Al-Eidan 2000 (8)
Yasunaga 2012 (9)
Wilcox 1996 (10)
Campbell 2013 (11)
Jiang 2013 (12)
Pant 2013 (13)
Quimbo 2013 (14)
Sammons 2013 (15)
Tabak 2013 (16)
Wilson 2013 (17)
Ali 2012 (18)
Kim 2012 (19)
Kuntz 2012 (20)
Lipp 2012 (21)
McGlone 2012 (22)
Pant 2012 (23)
Pant 2012 (24)
Peery 2012 (25)
Verlee 2012 (26)
Arora 2011 (27)
Glance 2011 (28)
Lesperance 2011 (29)
Nylund 2011 (30)
Pakyz 2011 (31)
Stewart 2011 (32)
Wang 2011 (33)
Bajaj 2010 (34)
Fuller 2009 (35)
Reed 2009 (36)
Zilberberg 2009 (37)
Ananthakrishnan 2008 (38)
Dubberke 2008 (39)
Nguyen 2008 (40)
1
[+]
+
+
+
+
+
+
+
+
+
+
[+]
+
+
+
+
+
+
+
+
+
+
[+]
+
+
+
-
2
+
NA
+
+
+
+
+
NA
+
NA
+
NA
+
+
+
+
NA
NA
NA
+
+
+
NA
NA
+
+
+
+
+
NA
+
NA
3
+
+
+
+
+
[+]
-
4
-
5
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
6
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
7
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
8
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
9
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
10
[+]
[+]
[+]
+
+
+
[+]
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
[+]
+
+
+
+
+
+
+
+
+
+
+
+
11
[+]
[+]
[+]
[+]
[+]
[+]
[+]
+
+
+
+
+
[+]
+
[+]
+
[+]
[+]
[+]
[+]
+
12
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
13
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
14
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
15
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
16
+
[+]
+
[+]
+
[+]
+
+
+
+
+
+
+
+
+
[+]
+
+
+
[+]
[+]
[+]
[+]
[+]
+
+
+
+
+
[+]
+
+
+
+
+
17
+
+
+
[+]
[+]
-
18
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
19
NA
NA
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
+
NA
NA
NA
NA
NA
NA
NA
NA
+
NA
+
NA
NA
NA
NA
NA
NA
NA
20
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
21
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
22
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
9
Country
Author and year
Song 2008 (41)
Lawrence 2007 (42)
O'Brien 2007 (43)
Zerey 2007 (44)
Kyne 2002 (45)
McFarland 1999 (46)
Kofsky 1991 (47)
Yannelli 1988 (48)
1
+
+
+
+
+
-
2
+
NA
+
+
NA
+
NA
3
+
+
-
4
-
5
+
+
+
+
+
+
+
-
6
+
+
+
+
+
+
+
-
7
NA
NA
NA
NA
NA
NA
NA
NA
8
NA
NA
NA
NA
NA
NA
NA
NA
9
+
+
+
+
+
+
+
10
+
+
+
+
+
+
+
-
11
+
+
[+]
-
12
+
+
+
+
+
+
+
+
13
NA
NA
NA
NA
NA
NA
NA
NA
14
NA
NA
NA
NA
NA
NA
NA
NA
15
NA
NA
NA
NA
NA
NA
NA
NA
16
[+]
+
[+]
+
+
[+]
[+]
-
17
-
18
NA
NA
NA
NA
NA
NA
NA
NA
19
NA
NA
NA
NA
NA
NA
NA
NA
20
+
+
[+]
+
+
-
21
+
+
+
+
+
22
+
+
+
+
+
+
-
1 The research question is stated; 2 The economic importance of the research question is stated; 3 The viewpoint(s) of the analysis are clearly stated and justified; 4 The form of economic evaluation used is
stated; 5 The primary outcome measure(s) for the economic evaluation are clearly stated; 6 Details of the subjects from whom valuations were obtained are given; 7 Productivity changes (if included) are
reported separately; 8 The relevance of productivity changes to the study question is discussed; 9 Quantities of resources are reported separately from their unit costs; 10 Methods for the estimation of
quantities and unit costs are described; 11 Currency and price data are recorded; 12 Time horizon of costs and benefits is stated; 13 The discount rate(s) is stated; 14 The choice of rate(s) is justified; 15 An
explanation is given if costs or benefits are not discounted; 16 Details of statistical tests and confidence intervals are given for stochastic data; 17 The approach to sensitivity analysis is given; 18 The choice of
variables for sensitivity analysis is justified; 19 The ranges over which the variables are varied are stated; 20 Incremental analysis is reported; 21 Major outcomes are presented in a disaggregated as well as
aggregated form; 22 Conclusions are accompanied by the appropriate caveats; “+” refers to “yes”; “[+]” refers to “partially”; “-“ refers to “no”; “NA” refers to “not applicable”; Questions 1 to 22 are from
Drummond and Jefferson (1); See Supplementary Table 2 for our interpretation of each question; Table format is based on Davis et al (49).
10
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14