title: Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40-80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR.
  
  
  METHODS
  A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies.
  
  
  RESULTS
  QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £ 300), increasing to £ 49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively.
  
  
  CONCLUSIONS
  Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.
authors: HEOR Ltd, Singleton Court Business Park, Monmouth, Wales, United Kingdom; Swansea Centre for Health Economics, School of Human & Health Sciences, Swansea University, Wales, United Kingdom.
authors: Phil
authors: P
authors: McEwan
authors: HEOR Ltd, Singleton Court Business Park, Monmouth, Wales, United Kingdom; Swansea Centre for Health Economics, School of Human & Health Sciences, Swansea University, Wales, United Kingdom.
authors: Thomas
authors: T
authors: Ward
authors: HEOR Ltd, Singleton Court Business Park, Monmouth, Wales, United Kingdom.
authors: Hayley
authors: H
authors: Bennett
authors: Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, United States of America.
authors: Anupama
authors: A
authors: Kalsekar
authors: HEOR Ltd, Singleton Court Business Park, Monmouth, Wales, United Kingdom.
authors: Samantha
authors: S
authors: Webster
authors: Bristol-Myers Squibb, Uxbridge, Middlesex, United Kingdom.
authors: Michael
authors: M
authors: Brenner
authors: Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, United States of America.
authors: Yong
authors: Y
authors: Yuan
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000191:economics* / Q000401:mortality / Q000821:virology*; D006801:Humans; D008017:Life Expectancy; D016014:Linear Models; D008099:Liver / Q000473:pathology; D008875:Middle Aged; D008954:Models, Biological; D019057:Quality-Adjusted Life Years; D006113:United Kingdom / Q000453:epidemiology
references: Health Technol Assess. 2000;4(33):1-67
references: 11134916
references: Gut. 2002 Feb;50(2):253-8
references: 11788569
references: BMJ. 2002 Feb 23;324(7335):450-3
references: 11859045
references: Acta Gastroenterol Belg. 2002 Apr-Jun;65(2):104-9
references: 12148430
references: Health Technol Assess. 2004 Oct;8(39):iii-iv, 1-125
references: 15461877
references: Gut. 2006 Sep;55(9):1332-8
references: 15994216
references: Epidemiol Infect. 2006 Jun;134(3):472-7
references: 16255834
references: Hepatology. 2007 Mar;45(3):579-87
references: 17326216
references: Health Technol Assess. 2007 Mar;11(11):1-205, iii
references: 17346498
references: J Hepatol. 2008 Jan;48(1):148-62
references: 18022726
references: Br J Cancer. 2008 Apr 8;98(7):1166-75
references: 18382459
references: Hepatology. 2008 Aug;48(2):418-31
references: 18563841
references: Int J Technol Assess Health Care. 2009 Apr;25(2):171-80
references: 19331708
references: Hepatology. 2009 Aug;50(2):407-13
references: 19575364
references: Liver Transpl. 2010 Jun;16(6):748-59
references: 20517909
references: Gastroenterology. 2010 Nov;139(5):1593-601
references: 20637202
references: J Theor Biol. 2011 Apr 7;274(1):58-66
references: 21236265
references: N Engl J Med. 2011 Mar 31;364(13):1195-206
references: 21449783
references: N Engl J Med. 2011 Jun 23;364(25):2405-16
references: 21696307
references: Hepatology. 2012 Jan;55(1):49-57
references: 21898506
references: Value Health. 2011 Dec;14(8):1068-77
references: 22152176
references: Clin Exp Gastroenterol. 2012;5:11-21
references: 22427726
references: Ther Clin Risk Manag. 2012;8:105-30
references: 22442631
references: Med J Aust. 2012 Jun 4;196(10):629-32
references: 22676877
references: QJM. 2013 Feb;106(2):153-63
references: 23159839
references: Appl Health Econ Health Policy. 2013 Feb;11(1):53-63
references: 23329380
references: Hepatology. 2013 Jul;58(1):54-64
references: 23389841
references: Hepatology. 2013 Oct;58(4):1253-62
references: 23564522
references: N Engl J Med. 2013 May 16;368(20):1878-87
references: 23607594
references: Hepatology. 2013 Dec;58(6):1918-29
references: 23907700
references: JAMA Intern Med. 2014 Feb 1;174(2):204-12
references: 24193887
references: Lancet. 2014 Feb 8;383(9916):515-23
references: 24209977
references: J Hepatol. 2014 Feb;60(2):392-420
references: 24331294
references: N Engl J Med. 2014 Jan 16;370(3):211-21
references: 24428467
references: Aliment Pharmacol Ther. 2014 Jun;39(12):1363-75
references: 24754233
references: Hepatology. 2014 Sep;60(3):807-14
references: 24919583
references: Value Health Reg Issues. 2014 May;3:5-11
references: 29702937