Submission to Applied Health Economics and Health Policy

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

1Division 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;

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

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 myelogenousleuk* OR chronic myeloid leuk*)

AND (decision anal* OR decision-anal* OR cost-utility OR costutility OR cost-benefit OR cost benefit OR cost-minimi* OR cost minimi* OR QALY Or Markov OR cost-effectiveness OR cost effectiveness OR healthcaremodel OR decision model OR decision-model OR decisiontree 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'/ montecarlo 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 myelogenousleukaemia

1

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 discount rate / Cost-effectiveness/ utility relation in US $ (October 2011) ¥, † / Cost-effectiveness/ utilityrelation / Conclusions
Pre-imatinib era
Beck et al. 2001[3],
university medical centers in North America & Europe / CEA, CUA, U.S.$,
estimated 2000 / 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
IFNαvs 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: $16,900/ QALY / “For all plausible ranges of the efficacy of IFNα and cytarabine, the combination therapies are cost-effective with respect to chemotherapy alone.” Further,” the increment in costs with cytarabine added to IFNα is more than offset by the extra increment in QALE.”
Kattan et al. 1996[4],
university medical centers North America & Europe / CEA, CUA, U.S.$,
estimated 1995 / Efficacy: RCTs, published studies, clinician panel
QoL/Utilities: Clinical panel: Direct scaling
Costs: U.S./ 2 European cancer centers, clinical-cost accounting systems / 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: $34,800/ QALY / “Compared with HU, IFNα is, in most clinical scenarios, a cost-effective initial therapy for patients with chronic-phase CML who can tolerate the drug.”
Liberato et al. 1997[5],
Italy / CUA, U.S.$,
1995 / Efficacy: RCTs, published studies QoL/Utilities: 10 physicians: VAS
Costs: Retail drug prices; published literature, expert panel judgments / 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: $63,500/ QALY / “In conclusion, IFNα adds an effective option to the treatment of CML, but is expensive in the most common protocols.”
Messori 1998[6],
German/English, Italian/Japanesetrials / CEA, U.S.$,
estimated 1997 / 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.”
Imatinib era
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 / 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 / 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: 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 / Benefits and costs: 3% / ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $53,841/ LYS,
($48,844/ LYS)
ICUR discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $54,091/ QALY
($51,843/ QALY) / ICER discounted (undiscounted)
Imatinib vs. IFNα+LDAC: $43,100/ LYS,
($39,100/ LYS)
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 / 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/ inpatient costs: Medicare / 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)
Imatinib vs. IFNα+LDAC
using AWP: $63,656/ QALY ($60,050/ QALY);
using WAC: $51,370/ QALY ($49,106/ QALY) / 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)
Imatinib vs. IFNα+LDAC
using AWP: $57,103/ QALY ($53,868/ QALY)
using WAC: $46,082/ QALY ($44,051/ QALY) / “Although the analysis revealed that the original survival estimates were conservative, the updated cost-effectiveness ratios were consistent with, or slightly higher than, the original estimates, depending on the method for assigning costs to study medications.”
Warren et al. 2004[12],
U.K. / CUA , £,
2001 / Efficacy: RCTs, published studies
QoL/Utilities: Panel of clinicians: EQ-5D
Costs: BNF, NHS reference costs, Personal Social Services Research Unit, authors' assumptions / Benefits: 1.5%,
Costs: 6% / ICUR discounted
Imatinib vs. HU: $77,880/ QALY / ICUR discounted
Imatinib vs. HU: £38,468/ QALY / "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."
Second-generation TKIs
Ghatnekar et al. 2010[13],
Sweden / CEA, CUA, €,
2008 / Efficacy: RCT (12 week head-to-head), 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 / 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 / “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.”
Hoyle et al, 2011[14](Rogers et al. 2012[15]),
U.K. / CEA, CUA, £,
2009-2010 / Efficacy: several trials from systematic review
QoL/Utilities:adopted from Reed[8, 11]
Costs: Expert opinion, trials, BNF, Curtis / Benefits and costs: 3.5% / Imatinib intolerant:
ICER discounted
Dasatinibvs. 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
$145,226/ QALY
Nilotinib vs. high dose-imatinib: Nilotinib dominates / 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
Nilotinib vs. high dose-imatinib: Nilotinib dominates / “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 cost-effective versus IFNα for people intolerant to imatinib.”
Loveman et al. 2012[16] / CEA, CUA ,£,
2009-2010 / Parameters mostly adopted from Hoyle et al.[14] (Rogers et al.[15]),
Drug costs: BNF / Costs and benefits 3.5% / ICUR discounted:
Nilotinib vs. HU: $41,956/ QALY
Dasatinib vs. Nilotinib: $79,385/ QALY
Remaining strategies were dominated / ICUR discounted
Nilotinib vs.HU: £26,434 / QALY
Dasatinib vs. nilotinib: £50,016 / QALY
Remaining strategies were dominated / “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 cost-effectiveness of the three interventions owing to the great uncertainty around data inputs.”
Pavey et al. 2012[17] / CEA, CUA, £,
2011-2012 / 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 / 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 cost-saving
Imatinib+2LNilo vs. dasatinib+2LNilo: $295,757/ LY
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 / 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
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 / “… 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.
BMT/ peripheral SCT
Breitscheidel 2008[19],
Germany / CUA, €,
2005 / 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 / Benefits and costs: 3% / ICUR discounted (undiscounted)
Imatinib vs. MUD-SCT: $92,594/ QALY ($102,752/ QALY) / ICUR discounted (undiscounted)
Imatinib vs. MUD-SCT: €69,764/ QALY (€77,410/ QALY) / “Imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of €77,410/ QALY is higher than commonly cited thresholds.”
Lee et al. 1997[18],
IBMTR, NMDP U.S. / UA / Efficacy: Published studies, clinician panel
QoL/Utilities: 12 physicians: STG
Costs: Not evaluated / Benefits: 3%,
Costs: not evaluated / Unadjusted LE (in years)
1)No BMT: 5.31
2)BMT within 1 year: 17.01
3)BMT at 1 to 2 years: 13.26
4)BMT at 2 to 3 years: 11.90
5)BMT at >3 years: 12.65
QALE discounted (in years)
1)No BMT: 4.74
2)BMT within 1 year: 10.07
3)BMT at 1 to 2 years: 8.11
4)BMT at 2 to 3 years: 7.51
5)BMT at >3 years: 8.08 / “These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.”
Lee et al. 1998[20],
U. S. / CUA , US$,
1996 / 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, pPatient 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: $55,500/ QALY / “Unrelated donor transplantation for CML is expensive in absolute costs, but because it prolongs life substantially for some patients, the ratio of costs to effectiveness is in the range of other well-accepted medical interventions.”
Skrepnek and Ballard 2005[21],
U.S. / CEA U.S.$,
2004 / 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."

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 (EinheitlicherBewertungsmaßstabderkassenärztlichenBundesvereinigung); 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 year; LYS =Life years saved; 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 ( 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].

1

Reason study exclusion last step

Table III: Reason for study exclusion (1)

Reference / ReasonforExclusion
Anonymous 2003[22] / Study Type
Anstrom 2004[23] / Model*
Baccarani 1992[24] / Publication Type
Bottemann 2010[25] / Publication Type
Garside 2002[26] / Model
Goldman 2005[27] / Publication Type
Gratwohl 2007[28] / Publication Type
Hoyle 2011[29] / Study Type
Kasteng 2007[30] / Study Type
McGlave 1992[31] / Study Type
Redaelli 2003[32] / Study Type
Roeder 2008[33] / Study Type
Roeder 2006[34] / Study Type
Shen 2009[35] / Publication Type
Simon 2006[36] / Model
Stephens 2010[37] / Intervention
Taylor 2009[38] / Publication Type

*Used as Background in Reed 2004[8]and 2008[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 Type / No full texts available (e.g., only abstract, or comment or letter)

References