Submission to Applied Health Economics and Health Policy
Systematic Assessment of Decision-analytic Models for Chronic
Myeloid Leukemia
Ursula Rochau1,2, Ruth Schwarzer1,2, Beate Jahn1,2, Gaby Sroczynski1,2, Martina
Kluibenschaedl1,2, Dominik Wolf3,4, Jerald Radich5, Diana Brixner1,2,6, Guenther
Gastl3, Uwe Siebert1,2,7,8
1
Division of Public Health Decision Modelling, Health Technology Assessment and Health Economics, ONCOTYROL -
Center for Personalized Cancer Medicine, Innsbruck, Austria;
2
Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health
and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall
i.T., Austria;
3
Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Austria;
4
Internal Medicine III, University of Bonn, Germany;
5
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;
6
Department of Pharmacotherapy and Program in Personalized Health Care, University of Utah, Salt Lake City, Utah,
USA;
7
Center for Health Decision Science, Department of Health Policy and Management, Harvard School of Public Health,
Boston, MA, USA;
8
Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA;
1
Corresponding Author:
Dr. Ursula Rochau, MSc
Area 4: Health Technology Assessment and Bioinformatics
ONCOTYROL - Center for Personalized Cancer Medicine
Innrain 66a
A – 6020 Innsbruck
Austria
T: +43(0)50-8648-3947, F: +43(0)50-8648-673947
ursula.rochau@oncotyrol.at
Online Supplementary Material 1
Literature search
NHS EED via OVID (update search date: 20.8.2013), (Pre-)Medline (update
20.8.2013) via OVID: Search fields: title, text, subject heading word, EMBASE via
Harvard (update 20.8.2013): Search fields: title, abstract, particularity in EMBASE:
adding German syntax
Keywords: (CML OR chronic myelogenous leuk* OR chronic myeloid leuk*)
AND (decision anal* OR decision-anal* OR cost-utility OR cost utility OR cost-benefit
2
OR cost benefit OR cost-minimi* OR cost minimi* OR QALY Or Markov OR costeffectiveness OR cost effectiveness OR health care model OR decision model OR
decision-model OR decision tree OR decision-tree OR health care evaluation model
OR discrete event simulation OR discrete OR individual simulation OR transmission
model OR AUC OR area under the curve model OR survival partition model)
MeSH: leukemia, myelogenous, chronic, bcr-abl positive/ or leukemia, myeloid,
chronic, atypical, bcr-abl negative/; markov chain'/ monte carlo method/ 'quality
adjusted life year'/ "Quality of Life"/cost-benefit analysis'/ area under curve'/ cost
utility analysis'/ decision tree'/ Models, Economic/
A restricted search was performed in EconLit via Harvard (update search date:
8.9.2013) and Tufts CEA Registry. Econlit: TI=cml OR TI=(leukemia or leukaemia)
A broader search was performed inTufts CEA Registry.
TI: CML OR Chronic Myeloid Leukemia OR Chronic Myeloid Leukaemia OR chronic
myelogenous
leukemia
OR
chronic
3
myelogenous
leukaemia
Table II: Summary of Cost-Effectiveness Results and Conclusions of Included Studies[1, 2]
Author, year,
country
Study type,
currency,
index year
Data sources
Annual
discoun
t rate
Cost-effectiveness/ utility relation in US $
Beck et al.
2001[3],
university
medical centers
in North
America &
Europe
CEA, CUA,
U.S.$,
estimated
2000
Kattan et al.
1996[4],
university
medical centers
North America
& Europe
CEA, CUA,
U.S.$,
estimated
1995
Liberato et al.
1997[5],
Italy
CUA, U.S.$,
1995
Messori
1998[6],
German/Englis
h,
Italian/Japanes
e trials
CEA, U.S.$,
estimated
1997
Cost-effectiveness/ utility relation
Conclusions
Efficacy: RCT (FCMLG)
QoL/Utilities: Updated Kattan et al.
1996[4]
Costs: Updated Kattan et al. 1996[4]
Benefits
and
costs:
3%
ICER discounted
IFNα vs. HU: $23,491/ LY
Cytarabine+IFNα vs. HU: $22,708/ LY
Cytarabine+IFNα vs. IFNα: $20,881/ LY
ICUR discounted
IFNα vs HU: $30,930/ QALY
Cytarabine+IFNα vs. HU: $27,994/ QALY
Cytarabine+IFNα vs. IFNα: $22,056/ QALY
ICER discounted
IFNα vs. HU: $18,000/ LY
Cytarabine+IFNα vs. HU: $17,400/ LY
Cytarabine+IFNα vs. IFNα: $16,000/ LY
ICUR discounted
IFNα vs. HU: $23,700/ QALY
Cytarabine+IFNα vs. HU: $21,450/ QALY
Cytarabine+IFNα vs. IFNα: $16,900/ QALY
“For all plausible ranges of the efficacy
of IFNα and cytarabine, the
combination therapies are costeffective with respect to chemotherapy
alone.” Further,” the increment in costs
with cytarabine added to IFNα is more
than offset by the extra increment in
QALE.”
Efficacy: RCTs, published studies,
clinician panel
QoL/Utilities: Clinical panel: Direct
scaling
Costs: U.S./ 2 European cancer
centers, clinical-cost accounting
systems
Efficacy: RCTs, published studies
QoL/Utilities: 10 physicians: VAS
Costs: Retail drug prices; published
literature, expert panel judgments
Benefits
and
costs:
5%
ICER discounted
IFNα vs. HU: $39,078/ year of life saved
ICUR discounted
IFNα vs. HU: $51,317/ QALY
ICER discounted
IFNα vs. HU: $26,500/ year of life saved
ICUR discounted
IFNα vs. HU: $34,800/ QALY
“Compared with HU, IFNα is, in most
clinical scenarios, a cost-effective
initial therapy for patients with chronicphase CML who can tolerate the
drug.”
Benefits
and
costs:
5%
ICUR discounted
IFNα Scenario A vs. chemotherapy:
$131,981/ QALY
IFNα Scenario B vs. chemotherapy: $93,640/
QALY
ICUR discounted
IFNα Scenario A vs. chemotherapy: $89,500/
QALY
IFNα Scenario B vs. chemotherapy: $63,500/
QALY
“In conclusion, IFNα adds an effective
option to the treatment of CML, but is
expensive in the most common
protocols.”
Efficacy: 4 RCTs
QoL/Utilities: Not evaluated
Costs: Published literature
Benefits
and
costs:
5%
ICER discounted
IFNα vs. control group
1)German trial: $130,866/ LY
2)English trial: $180,724/ LY
3)Italian trial: $236,617/ LY
4)Japanese trial: $317,214/ LY
ICER discounted
IFNα vs. control group
1)German trial: $93,461/ LY
2)English trial: $129,068/ LY
3)Italian trial: $168,985/ LY
4)Japanese trial: $226,545/ LY
“Our cost-effectiveness study gave a
'negative' result because our findings
showed that an unselected use of
IFNα in CML has an unfavorable
pharmacoeconomic ranking.”
(October 2011) ¥, †
Pre-imatinib era
Imatinib era
4
Author, year,
country
Study type,
currency,
index year
Data sources
Annual
discoun
t rate
Cost-effectiveness/ utility relation in US $
Cost-effectiveness/ utility relation
Conclusions
Chen et al.
2009[7],
China
CEA, CUA,
RMB,
estimated
2008
Efficacy: RCTs (incl. IRIS), published
studies
QoL/Utilities: Reed et al. 2004[8]
Costs: Retail price, unit costs top tier
hospitals
Efficacy: RCTs, published studies
QoL/Utilities: Patients (IRIS): EQ-5D
(Imatinib, IFNα), estimates clinical
panel from Kattan et al. 1996[4] (HU)
Costs: BNF, SUHT, NHS Trust
databases
Benefits
and
costs:
3.5%
ICER discounted
Imatinib vs. IFNα: $20,463/ LY
ICUR discounted
Imatinib vs. IFNα: $20,126/ QALY
ICER discounted
Imatinib vs. IFNα: RMB74,908/ LY
ICUR discounted
Imatinib vs. IFNα: RMB73,674/ QALY
“This study confirms that imatinib is
more cost-effective than IFNα from the
Chinese public health-care system
perspective“.
Dalziel et al.
2004[9],
U.K.
CUA, £,
2002
Benefits:
1.5%,
Costs:
6%
ICUR discounted (undiscounted)
Imatinib vs. IFNα: $52,108/ QALY ($63,217/
QALY)
Imatinib vs. HU: $173,033/ QALY ($167,393/
QALY)
ICUR discounted (undiscounted)
Imatinib vs. IFNα: £26,180/ QALY (£31,761/
QALY)
Imatinib vs. HU: £86,934/ QALY (£84,100/
QALY)
“Imatinib appears to be more effective
than current standard drug treatments
in terms of cytogenetic response and
PFS, with fewer side-effects.”
Gordois et al.
2003[10]
U.K.
CUA, £,
2001
Efficacy: RCTs, published studies,
clinician panel
QoL/Utilities: 6 clinicians using the
EQ-5D
Costs: Chartered Institute of Public
Finance and Accountancy, Dept. of
Health, 6 NHS Trusts, published
literature
Benefits:
1.5%,
Costs:
6%
ICUR discounted
Accelerated Phase
Imatinib vs. comparator: $59,408/ QALY
Blast Crisis Phase
Imatinib vs. comparator: $85,514/ QALY
ICUR discounted
Accelerated Phase
Imatinib vs. comparator: £ 29,344/ QALY
Blast Crisis Phase
Imatinib vs. comparator: £42,239/ QALY
"We conclude that treatment of CML
with imatinib confers considerably
greater survival and quality of life than
conventional treatments but at a cost."
Reed et al.
2004[8]
U.S.
CEA, CUA,
U.S.$,
2002
Efficacy: RCTs (incl. IRIS, FCMLG),
published studies
QoL/Utilities: Patients (IRIS): EQ-5D
(imatinib, IFNα+LDAC); no data HU:
imatinib utility values used
Costs: Medication costs: Red Book,
outpatient visits/inpatient costs:
Medicare
Efficacy: Reed et al. 2004[8]., update
IRIS
QoL/Utilities: Reed et al.2004[8]
Costs: Medications: AWP Red Book,
WAC, Medi-Span; outpatient visits/
Benefits
and
costs:
3%
ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $53,841/ LY,
($48,844/ LY)
ICUR discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $54,091/ QALY
($51,843/ QALY)
ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $43,100/ LY,
($39,100/ LY)
ICUR discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $43,300/ QALY
($41,500/ QALY)
“The results of the current study
demonstrate that compared with IFNα
plus LDAC, imatinib is a cost-effective
first-line therapy in patients with newly
diagnosed chronic-phase CML.”
Reed et al.
2008[11]
(update Reed
et al. 2004[8]),
U.S.
CEA, CUA,
U.S.$, 2006
Benefits
and
costs:
3%
ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC
using AWP: $59,679/ LY ($53,657/ LY);
using WAC: $48,124/ LY ($43,868/ LY)
ICUR discounted (undiscounted)
ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC
using AWP: $53,535/ LY ($48,133/ LY)
using WAC: $43,170/ LY ($39,352/ LY)
ICUR discounted (undiscounted)
“Although the analysis revealed that
the original survival estimates were
conservative, the updated costeffectiveness ratios were consistent
with, or slightly higher than, the
(October 2011) ¥, †
5
Author, year,
country
Study type,
currency,
index year
Data sources
Annual
discoun
t rate
inpatient costs: Medicare
Warren et al.
2004[12],
U.K.
CUA , £,
2001
Cost-effectiveness/ utility relation in US $
Cost-effectiveness/ utility relation
Conclusions
Imatinib vs. IFNα+LDAC
using AWP: $63,656/ QALY ($60,050/ QALY);
using WAC: $51,370/ QALY ($49,106/ QALY)
ICUR discounted
Imatinib vs. HU: $77,880/ QALY
Imatinib vs. IFNα+LDAC
using AWP: $57,103/ QALY ($53,868/ QALY)
using WAC: $46,082/ QALY ($44,051/ QALY)
ICUR discounted
Imatinib vs. HU: £38,468/ QALY
original estimates, depending on the
method for assigning costs to study
medications.”
"In the present model analysis,
imatinib as a second-line treatment for
patients with chronic phase CML was
found to offer considerable health
benefits to patients, but at a cost to the
payer."
“The results indicate that dasatinib
treatment in CML patients resistant to
standard dose imatinib in Sweden is a
cost-effective treatment in comparison
to imatinib 800 mg/daily. Dasatinib is
expected to generate greater health
benefits at a cost per QALY of about
€6,880 with a life-long societal
perspective.”
“Whilst clinical data remains immature,
the cost-effectiveness of dasatinib and
nilotinib for imatinib-resistant people is
highly uncertain. Both nilotinib and
dasatinib are highly unlikely to be costeffective versus IFNα for people
intolerant to imatinib.”
(October 2011) ¥, †
Efficacy: RCTs, published studies
QoL/Utilities: Panel of clinicians: EQ5D
Costs: BNF, NHS reference costs,
Personal Social Services Research
Unit, authors' assumptions
Benefits:
1.5%,
Costs:
6%
Efficacy: RCT (12 week head-tohead), published literature
QoL/Utilities: 100 U.K. lay persons:
TTO using the EQ-5D
Costs: Treatment practice: 2 Swedish
hematologists; Unit cost: FASS,
regional tariffs and fees, income
distribution survey, consumption and
production in Sweden
Efficacy: several trials from systematic
review
QoL/Utilities: adopted from Reed[8,
11]
Costs: Expert opinion, trials, BNF,
Curtis
Benefits
and
costs:
3%
ICER discounted
Dasatinib vs. Imatinib: $8,167/ LY
ICUR discounted
Dasatinib vs. Imatinib: $8,873/ QALY
ICER discounted
Dasatinib vs. Imatinib: €6,332/ LY
ICUR discounted
Dasatinib vs. Imatinib: €6,880/ QALY
Benefits
and
costs:
3.5%
Imatinib intolerant:
ICER discounted
Dasatinib vs. IFNα : $76,107/ LY
Nilotinib vs. IFNα : $108,833/ LY
ICUR discounted
Dasatinib vs. IFNα : $131,132/ QALY
Nilotinib vs. IFNα: $166,175/ QALY
Imatinib resistant
ICER discounted
Dasatinib vs. high dose-imatinib: $74,841/ LY
Nilotinib vs. high dose-imatinib: Nilotinib
dominates
ICUR discounted
Dasatinib vs. high dose-imatinib
Imatinib intolerant:
ICER discounted
Dasatinib vs. IFNα: £47,951/ LY
Nilotinib vs. IFNα: £68,570/ LY
ICUR discounted
Dasatinib vs. IFNα: £82,619/ QALY
Nilotinib vs. IFNα: £104,698 QALY
Imatinib resistant:
ICER discounted
Dasatinib vs. high dose-imatinib: £47,153/ LY
Nilotinib vs. high dose-imatinib: Nilotinib
dominates
ICUR discounted
Dasatinib vs. high dose-imatinib: £91,499/ QALY
Second-generation TKIs
Ghatnekar et al.
2010[13],
Sweden
CEA, CUA,
€,
2008
Hoyle et al,
2011[14]
(Rogers et al.
2012[15]),
U.K.
CEA, CUA,
£,
2009-2010
6
Author, year,
country
Loveman et al.
2012[16]
Pavey et al.
2012[17]
Study type,
currency,
index year
CEA, CUA ,
£,
2009-2010
CEA, CUA,
£,
2011-2012
Data sources
Parameters mostly adopted from
Hoyle et al.[14] (Rogers et al.[15]),
Drug costs: BNF
Efficacy: several trials from systematic
review
QoL/Utilities: adapted from Reed[8],
Lee[18], Dalziel[9]
Costs: BNF, MIMS, Oxford Outcomes
2009 survey, (NSRC), Curtis, trials
and manufacturer submissions
Annual
discoun
t rate
Cost-effectiveness/ utility relation in US $
Cost-effectiveness/ utility relation
Conclusions
(October 2011) ¥, †
$145,226/ QALY
Nilotinib vs. high dose-imatinib: Nilotinib
dominates
Nilotinib vs. high dose-imatinib: Nilotinib
dominates
Costs
and
benefits
3.5%
ICUR discounted:
Nilotinib vs. HU: $41,956/ QALY
Remaining strategies were dominated
ICUR discounted
Nilotinib vs.HU: £26,434 / QALY
Dasatinib vs. nilotinib: £50,016 / QALY
Remaining strategies were dominated
Costs
and
benefits
3.5%
Scenario 1
ICER discounted
Nilotinib vs. imatinib: $17,657/ LY
Dasatinib vs. imatinib: $301,643/ LY
Nilotinib vs. dasatinib: $-142,728/ LY
ICUR discounted:
Nilotinib vs. imatinib: $36,786/ QALY
Dasatinib vs. imatinib: $609,172/ QALY
Nilotinib vs. dasatinib: Dasatinib dominated
Scenario 2
ICUR discounted:
Nilotinib vs. imatinib: $29,429/ QALY
Dasatinib vs. imatinib: $376,686/ QALY
Nilotinib vs. dasatinib: Dasatinib dominated
Scenario 3
ICER discounted
Imatinib+2LNilo vs. nilotinib: Nilotinib costsaving
Imatinib+2LNilo vs. dasatinib+2LNilo:
$295,757/ LY
Scenario 1
ICER discounted
Nilotinib vs. imatinib: £12,000/ LY
Dasatinib vs. imatinib: £205,000/ LY
Dasatinib vs. nilotinib: Dasatinib dominated
ICUR discounted:
Nilotinib vs. imatinib: £25,000/ QALY
Dasatinib vs. imatinib: £414,000/ QALY
Dasatinib vs. nilotinib: Dasatinib dominated
Scenario 2
ICUR discounted:
Nilotinib vs. imatinib: : £20,000/ QALY
Dasatinib vs. imatinib: £256,000/ QALY
Dasatinib vs. nilotinib: : Dasatinib dominated
Scenario 3
ICER discounted
Imatinib+2LNilo vs. nilotinib: Nilotinib cost-saving
Imatinib+2LNilo vs. dasatinib+2LNilo: £201,000/
LY
Nilotinib vs. dasatinib+2LNilo: £356,000/ LY
Dasatinib vs. Nilotinib: $79,385/ QALY
7
“Nilotinib and dasatinib are slightly
more cost-effective than high-dose
imatinib because of slightly lower
costs and better effectiveness than
high-dose imatinib.”
“It is not possible to derive firm
conclusions about the relative costeffectiveness of the three interventions
owing to the great uncertainty around
data inputs.”
“… assuming the use of
second-line nilotinib, first-line nilotinib
appears to be more cost-effective than
first-line imatinib for most scenarios.
Dasatinib was not cost-effective if
decision thresholds of £20,000 per
QALY or £30,000 per QALY are used,
compared with imatinib and nilotinib.
Author, year,
country
Study type,
currency,
index year
Data sources
Annual
discoun
t rate
Cost-effectiveness/ utility relation in US $
Cost-effectiveness/ utility relation
Conclusions
(October 2011) ¥, †
Nilotinib vs. dasatinib+2LNilo: $523,829/ LY
ICUR discounted:
Imatinib+2LNilo vs. nilotinib: $282,515/ QALY
Imatinib+2LNilo vs. dasatinib+2LNilo:
$662,144/ QALY
Nilotinib vs. dasatinib+2LNilo: $507,643/
QALY
Scenario 4
Imatinib+2LNilo vs. nilotinib: $67,686/ QALY
Imatinib+2LNilo vs. dasatinib+2LNilo:
$442,900/ QALY
Nilotinib vs. dasatinib+2LNilo: $183,929/
QALY
ICUR discounted:
Imatinib+2LNilo vs. nilotinib: £192,000/ QALY
Imatinib+2LNilo vs. dasatinib+2LNilo: £450,000/
QALY
Nilotinib vs. dasatinib+2LNilo: £345,000/ QALY
Scenario 4
Imatinib+2LNilo vs. nilotinib: £46,000/ QALY
Imatinib+2LNilo vs. dasatinib+2LNilo: £301,000/
QALY
Nilotinib vs. dasatinib+2LNilo: £125,000/ QALY
ICUR discounted (undiscounted)
Imatinib vs. MUD-SCT: $92,594/ QALY
($102,752/ QALY)
ICUR discounted (undiscounted)
Imatinib vs. MUD-SCT: €69,764/ QALY
(€77,410/ QALY)
“Imatinib is more costly but more
effective (as measured in QALYs) over
a 5-year time horizon. The resulting
ICER of €77,410/ QALY is higher than
commonly cited thresholds.”
Unadjusted LE (in years)
1)No BMT: 5.31
2)BMT within 1 year: 17.01
3)BMT at 1 to 2 years: 13.26
4)BMT at 2 to 3 years: 11.90
5)BMT at >3 years: 12.65
QALE discounted (in years)
1)No BMT: 4.74
2)BMT within 1 year: 10.07
3)BMT at 1 to 2 years: 8.11
4)BMT at 2 to 3 years: 7.51
5)BMT at >3 years: 8.08
“These results support the use of early
unrelated donor bone marrow
transplantation for most patients with
CML.”
BMT/ peripheral SCT
Breitscheidel
2008[19],
Germany
CUA, €,
2005
Lee et al.
1997[18],
IBMTR, NMDP
U.S.
UA
Efficacy: RCT (IRIS), published
studies
QoL/Utilities: Patients (IRIS) EQ-5D
(Imatinib); clinical panel: STG
(rescaled, Lee et al. 1997[18], SCT)
Costs: Red Book, DRG, EBM
Efficacy: Published studies, clinician
panel
QoL/Utilities: 12 physicians: STG
Costs: Not evaluated
Benefits
and
costs:
3%
Benefits:
3%,
Costs:
not
evaluate
d
8
Author, year,
country
Study type,
currency,
index year
Data sources
Annual
discoun
t rate
Cost-effectiveness/ utility relation in US $
Lee et al.
1998[20],
U. S.
CUA , US$,
1996
Skrepnek and
Ballard
2005[21],
U.S.
CEA U.S.$,
2004
Cost-effectiveness/ utility relation
Conclusions
Efficacy: Meta-analysis of 7 RCTs,
Lee et al. 1997[18]
QoL/Utilities: Lee et al. 1997[18]
Costs: Medical costs: accounting
systems BWH, FHCRC; Medication
costs: AWP, Red Book, patient
records, published studies
Benefits
and
costs:
3%
ICUR discounted
BMT vs. IFNα: $74,196/ QALY
BMT vs. HU: $79,495/ QALY
ICUR discounted
BMT vs. IFNα: $51,800/ QALY
BMT vs. HU: $55,500/ QALY
“Unrelated donor transplantation for
CML is expensive in absolute costs,
but because it prolongs life
substantially for some patients, the
ratio of costs to effectiveness is in the
range of other well-accepted medical
interventions.”
Efficacy: RCTs (incl. IRIS), published
studies
QoL/Utilities: Not evaluated
Costs: Fee Reference, Physicians'
Fee and Coding Guide, average
wholesale prices; expert clinical
opinion; published data
Benefits:
n.r.,
Costs:
5%
ICER discounted
Markov cohort analysis:
Imatinib vs. BMT: -$90,167/ survival
Monte Carlo microsimulation:
Imatinib vs. BMT: -$5,948/ survival
ICER discounted
Markov cohort analysis:
Imatinib vs. BMT: -$75,789/ survival
Monte Carlo microsimulation:
Imatinib vs. BMT: -$5,000/ survival
"In most cases, imatinib was both less
costly and more efficacious than BMT
in the 2-year treatment of CML."
(October 2011) ¥, †
Legend:
AWP = Average wholesale prices; BMT = Bone marrow transplantation; BNF = British National Formulary; CEA = Cost-effectiveness
analysis; CML = Chronic myeloid leukemia; CUA = Cost-utility analysis; Curtis = Unit Costs of Health and Social Care; DRG = Diagnosis
Related Groups; EBM = German Common Tariff Scale (Einheitlicher Bewertungsmaßstab der kassenärztlichen Bundesvereinigung); EQ-5D
= EuroQol 5D questionnaire; FASS = Pharmaceutical specialties in Sweden; FCMLG = French Chronic Myeloid Leukemia Study Group; HU
= Hydroxyurea; IBMTR = International Bone Marrow Transplant Registry; ICER = Incremental cost-effectiveness ratio; ICUR = Incremental
cost-utility ratio; IFNα = Interferon-alpha; IRIS = International Randomized Study of Interferon and STI571; LE = Life expectancy; LY =Life
9
year; LDAC = Low-dose cytarabine; MIMS = Monthly Index of Medical Specialties; MUD-SCT = Allogeneic stem cell transplantation with a
matched unrelated donor; NHS = National Health Service; NMDP = National Marrow Donor Program; NHS = National Health Service; PFS =
Progression-free survival; QALE = quality-adjusted life expectancy; QALY = Quality-adjusted life year; QoL = Quality of Life; RCT =
Randomized Controlled Trial; RMB = Renminbi (Chinese currency); SCT = Stem cell transplantation; SUHT = Southampton University
Hospitals NHS Trust; TTO = time-tradeoff; U.K. = United Kingdom; U.S. = United States of America; VAS = Visual analogue scale; vs. =
versus; WAC = Wholesale acquisition costs; € = Euro; $ = U.S. Dollar; £ = Pounds sterling; & = And; 2LNilo = Second-line nilotinib
Footnotes (corresponding to table II)
When the index year used for the economic evaluation was not stated, it was estimated to be the year prior to publication.
Economic results were transferred into 2011 US Dollar for comparability. This was done in two steps:
¥ Converting the currency into US Dollar of the same year using Purchasing power parity (PPP) rates
(http://stats.oecd.org/Index.aspx?datasetcode=SNA_TABLE4)[2], for example, € 2004 transformed to US$ 2004
† Converting US Dollar from step one into US Dollars 2011 (ftp://ftp.bls.gov/pub/special.requests/cpi/cpiai.txt)[1].
10
Reason study exclusion last step
Table III: Reason for study exclusion (1)
1.
Reference
Reason for Exclusion
Anonymous
Study Type
2003[22]
2.
Anstrom 2004[23]
Model*
3.
Baccarani 1992[24] Publication Type
4.
Bottemann
Publication Type
2010[25]
5.
Garside 2002[26]
Model
6.
Goldman 2005[27]
Publication Type
7.
Gratwohl 2007[28]
Publication Type
8.
Hoyle 2011[29]
Study Type
9.
Kasteng 2007[30]
Study Type
10.
McGlave 1992[31]
Study Type
11.
Redaelli 2003[32]
Study Type
12.
Roeder 2008[33]
Study Type
13.
Roeder 2006[34]
Study Type
14.
Shen 2009[35]
Publication Type
15.
Simon 2006[36]
Model
16.
Stephens 2010[37]
Intervention
17.
Taylor 2009[38]
Publication Type
*Used as Background in Reed 2004[8]and 2008[11]
11
Table IV: Definition: Reason for study exclusion (2)
Reason
Explanation
Intervention
Does not evaluate a treatment for CML
Model
No Model or not sufficiently structured: based on
a decision-analytic model or any other type of
mathematical
healthcare
model
evaluating
therapeutic interventions for CML
Study Type
Purely descriptive studies or studies using
models only as an illustration or in a tutorial
were excluded
Publication
No full texts available (e.g., only abstract, or
Type
comment or letter)
12
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